FALL 2016
Communications with Alumni and Friends
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
Inside:
Alumni Profiles: Henry Fogel and Garth D. Ehrlich
Faculty Profiles: Robert B. Silver and Katharine Lewis
BIOLOGY.SYR.EDU
contents
3
28
14
20
30
26
Dean
Karin Ruhlandt
41
Photography
Steve Sartori
Lynn Fall
Co-Editors
Ernest Hemphill
Scott Erdman
Lynn Fall
Assistant Dean for
Advancement
Karen Weiss Jones
Copy Editor
George Bain
Address Updates
Lynn Fall ([email protected])
Design
SU Office of Publications
Syracuse University
Department of Biology
110 Life Sciences Complex
107 College Place
Syracuse NY 13244
315.443.2012
biology.syr.edu
Department Chair
Ramesh Raina
Letter from the Chair
1
Faculty Profile
Robert B. Silver
Katharine Lewis
3
9
Professor Scott Pitnick Awarded
Weeden Professor in the College of Arts and Sciences
14
Recent Faculty Hires
Carlos A. Castañedar
Jessic MacDonald
16
17
Undergraduate Student Profiles
Luke Strauskulage
Natalie Rebeyev
Komal Safdar
18
20
23
Staff Profile
Kelly Condon
25
Graduate Student Profiles
Liz Droge-Young
David Lemon
26
28
Alumni Profiles
Henry Fogel
Garth D. Ehrlich
30
32
Graduate Student News and Achievements
39
Undergraduate Activities and Achievements
40
Undergraduate Research Conference
42
Faculty News
43
Who, What, When, Where
44
Giving to the Biology Department at Syracuse University
45
ON THE COVER
Life Science Complex at night
FROM THE CHAIR
By Ramesh Raina
O
nce again it’s time for me to report the
many developments of the past year
in the Department of Biology and on
the Syracuse University campus. We
welcomed one new postdoctoral scientist, Hyuck
Kim (MacDonald lab). This brings our current
postdoc count to 18. Postdoctoral scientists are
critical components of the research mission of our
department and also often help provide guidance to
graduate and undergraduate researchers, enabling
more training opportunities in our faculty’s labs.
The department is also pleased to welcome back
Robin Jones (Ph.D. 2012 with Melissa Pepling) as a
lecturer in neuroscience and biology.
Our graduate students continue to excel in
research and scholarship, and they were recognized
by a variety of awards:
• Mason Heberling (Ph.D., Fridley lab) was
awarded the 2015 Alexander Gourevitch
Memorial Award, the Department of Biology’s
highest graduate student award, and an
Outstanding Dissertation Award from the
College of Arts and Sciences for the 2014-15
academic year.
• Elise Hinman (Ph.D., Fridley lab) was awarded
a National Science Foundation Doctoral
Dissertation Improvement Grant.
• Insu Jo (Ph.D., Frank and Fridley labs) was the
recipient of the 2015 Ecological Society of
America Asian Ecology Section Outstanding
Graduate Student Award.
• Kelsey Martinez (Ph.D., Fridley lab) was
awarded an East Asia and Pacific Summer
Institutes for U.S. Graduate Students grant
from the National Science Foundation to
support her research in Japan during summer
2016.
• Caitlin McDonough (Ph.D., Dorus and Pitnick
labs) was awarded a National Science
Foundation Graduate Research Fellowship.
• Luka Negoita (Ph.D., Fridley lab) was awarded
a National Science Foundation Doctoral
Dissertation Improvement Grant.
This past year we graduated four Ph.D. and
three M.S. students. They are Hannah Blair (M.S.,
Parks lab), Elisabeth Bodnaruk (M.S., Ritchie lab),
Nikhilesh Dhar (Ph.D., Raina lab), Mason Heberling
(Ph.D., Fridley lab), Insu Jo (Ph.D., Frank and Fridley
labs), Jessica McCordic (M.S., Parks lab), Megan
McSherry (Ph.D., Ritchie lab).
Some of our M.S. graduates joined Ph.D.
programs at prestigious institutions, while others
took up academic jobs. All of our Ph.D. graduates
joined postdoctoral positions in prestigious
institutions.
We admitted eight new graduate students
(seven Ph.D. and one M.S.), both domestic and
international. Three of these students are recipients
of various fellowships, including a Syracuse
University Graduate Fellowship, McNair and STEM
Fellowships, and an NSF graduate fellowship. Many
of our graduate students attended a variety of
national and international research conferences to
present their research work, and several received
best posters/oral presentation awards for their
presentations. Many of these travels were supported
in part by an endowment established by one of our
Biology Alumni Board members, Robert Hallenbeck
’82, and his wife, Susan. We are grateful to Bob
and Susan for their support, which makes travel
to research conferences by our graduate students
possible.
The number of biology, biochemistry, and
biotechnology undergraduates continues to grow;
currently we have more than 700 undergraduates
in these programs. This past year we graduated 131
biology, 31 biochemistry, and 17 biotechnology
majors. They did well in receiving highly prestigious
University awards. Four of our 2015 graduates were
FALL 2016
1
named Syracuse University Scholars, the highest
undergraduate academic honor bestowed at the
University. These students are Elizabeth McMahon,
Natalie Rebeyev, Elliott Russell, and Kristin Weeks.
Kristin Weeks was also selected to serve as a
college marshal for the College of Arts and Sciences
Convocation. In addition, these four students
received Remembrance Scholarships, among the
most prestigious scholarships the University awards.
For more information about these outstanding
students, please see page 40.
During spring semester, the Biology Department
holds Senior Honors Day to celebrate the
achievements of our graduating seniors. We
recognized 56 students from the class of 2015 for
academic excellence, research accomplishments,
or excellence in both academics and research.
Kristin Weeks was awarded the Donald G. Lundgren
Memorial Award for Outstanding Achievement
in Biology, Komal Safdar was awarded the
Outstanding Achievement in Biochemistry
award, and Luke Strauskulage was awarded the
Outstanding Achievement in Biotechnology award.
Nineteen seniors earned degrees with distinction
in recognition of their successful completion of a
high-quality research thesis, and 15 graduated with
honors. Please see page 40 for more information
about these accomplishments. These are some of
the testaments to the ongoing high quality of our
undergraduate students, and we continue to be
proud of their achievements.
This past year more than 100 undergraduates
were engaged in independent research in the
faculty labs. Many of these students received
research awards to support their research from
a variety of sources, including the Renée Crown
Honors Program, the Korczynski-Lundgren
Undergraduate Summer Research Fund, the LevyDaouk Fund, the Phillips Undergraduate Research
Fund, the Bishop Neuroscience Program Fund, and
the iLearn fund of the College of Arts and Sciences.
We gratefully acknowledge the generous gifts that
provide these sources of support that make it
possible for many of our undergraduate students to
carry out independent research.
Our faculty members continue to gain national
and international recognition for their outstanding
research contributions. In addition, they continue
to win research grants from federal and other
funding agencies. This year faculty members won
grants from the National Institutes of Health, the
National Science Foundation, New York State, the
National Park Service, the National Geographic
Society, and the Marine Mammal Commission. Kari
Segraves was the inaugural winner of the Center for
Fellowship and Scholarship Advising (CFSA) Mentor
2
of the Year award in recognition of her outstanding
mentoring and advising of undergraduate students
who we are applying for prestigious national and
international fellowships and scholarships. I would
also like to draw your attention to the recently
created research center, the Center for Reproductive
Evolution (CRE), a collaborative effort of faculty
members John Belote, Steve Dorus, Jannice
Friedman, and Scott Pitnick. Please visit cre.syr.
edu to learn more about the exciting research
being done at this center. Our students, postdocs,
and faculty continue to publish in national and
international journals of high visibility, and our
faculty members served as expert reviewers for
national and international funding agencies and
scientific journals, and on editorial boards.
We held a Biology Advisory Board (BAB) meeting
October 30-31, 2015, on campus. We are pleased
to welcome a new member to BAB, Laura Feldman
’81. Current members are Ghaleb Daouk ’79, Laura
Feldman ’81 (co-chair), Robert Hallenbeck ’82,
Mark Horowitz ’72, Michael Kurman ’73 (co-chair),
David Page ’78, and Jeffrey McMullen ’73. The BAB
meeting was also attended by Arts and Sciences
Board of Visitors members Jeffrey Bastable ’69,
Martin Gellert, and Alicia Carroll ’88, as well as
Arts and Sciences Dean Karin Ruhlandt, Associate
Dean Kandice Salomone, and Assistant Dean Karen
Weiss-Jones.
In last year’s BIO@SU, I told you about the
appointment of Professor Scott Pitnick as
inaugural Weeden Professor in the College of
Arts and Sciences. On October 30, 2015, the
Weeden Professor installation ceremony was
held in the morning followed by an open house
in the afternoon. As a part of the open house,
we organized a poster session in which our
undergraduates, graduate students, and postdocs
presented their research, and tours of the Life
Sciences Complex were organized for the members
of the Arte and Sciences Board of Visitors and
Biology Advisory Board. This well-attended event
was a huge success. The day concluded with a
dinner at the Goldstein Alumni and Faculty Center
attended by Interim Vice Chancellor Elizabeth
Liddy, Dean Karin Ruhlandt, members of the
biology department faculty and several students to
celebrate the Weeden Professor installation.
One of our most illustrious alumni, John Thomas
G’69, returned to the campus with his family 47
years after finishing his degree to participate in
the doctoral hooding ceremony. I had the distinct
pleasure and honor to hood him at this occasion.
Please visit asnews.syr.edu/newsevents_2016/
releases/john_thomas_award.html to read John’s
fascinating story.
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
The biology department website has been
revamped. I encourage you to visit us at biology.
syr.edu for the latest exciting news about the
department. Please go to the alumni page to know
more about our alumni activities.
As some of you might be aware, Professor Scott
Erdman concluded his term as associate chair and
director of undergraduate studies for the biology
department on June 30, 2016, and Professor
Melissa Pepling took over the charge from him.
I wish to take this opportunity to thank Scott for
his many contributions to the department in this
capacity, especially his tireless efforts to improve
our undergraduate program, and I look forward to
working with Melissa in the coming years.
This past spring the University welcomed our new
vice chancellor and provost, Michele Wheatly. She
comes to us from West Virginia University, where she
was provost from January 2010 through June 2014.
In addition to her administrative work, she is a
biologist who therefore also enjoys an appointment
as a faculty member in our department. All of us in
the University are looking forward to her leadership
in guiding Syracuse University through the next
phase of our development.
I wish to take this opportunity to thank Dean
Karin Ruhlandt, former Interim Vice Chancellor
and Provost Elizabeth Liddy, and Chancellor Kent
Syverud for their continued support of the biology
department. In addition, our alumni have always
been our strongest advocates and have provided
valuable support to our department, and I wish
to thank them for their ongoing support. Finally,
I would like to thank the co-editors of BIO@SU,
Professor Emeritus Ernie Hemphill Professor Scott
Erdman and Graduate Program Administrator Lynn
Fall for their commitment and efforts to produce
this wonderful publication each year to bring the
exciting news of the department to our alumni.
FACULTY PROFILE
How Cells Make Decisions: Thoughts on the
Process of Cell Division
Robert B. Silver, Ph.D.
B
iology is governed by fundamental
principles. Biologists occupy their efforts
and thoughts and dedicate their lives to
the study of those fundamental principles,
and to conveying those principles and findings to
the next generation of biologists to further their
efforts to reveal and understand those processes
and principles. It is a grand exploration and
endeavor.
Perhaps the most essential principle in biology
is that of reproduction, that is, the units of life must
reproduce or they will perish. The elemental unit in
biology is the living cell. Cells have a finite lifetime,
even with life-extension options such as the
formation of dormant spores. Mitosis, reproductive
spores, and sperm and eggs are vehicles to achieve
that organismal reproduction. In mitotically dividing
cells, the finite lifetime of the cell begins when
that cell is first formed and ends when, acting as a
mother cell, it divides to form two (identical) copies
of itself—the daughter cells. The period between the
formation of one cell and its reproductive formation
of two daughter cells is referred to as a cell cycle.
As such, the term cell cycle is a misnomer, in a
manner similar to that of a lifecycle, because the
so-called cell cycle is not a simple cycle but rather
is a bifurcation wherein one cell becomes two.
This bifurcation, yielding two competent
(vegetative) cells is not a given. One or both of
the daughter cells may die for any of a number
of reasons, including necrosis or apoptosis (i.e.,
programmed cell death). One cell may remain
vegetative while the other dies or becomes
specialized for a particular function and may be
amitotic (i.e., post-mitotic). In the case of early
embryos and germinative cell layers, the mother
cell gives rise to two equally competent daughter
cells. In deuterstomes, the first cleavage divisions
of the fertilized egg yields daughter cells that are
totipotent, that is, each of the daughter cells—called
blastomeres—has the potential to form a complete
embryo and ultimately a complete adult organism.
Thus, to understand the solution to how cells
make the decision to divide at its most fundamental
level, one could focus on the first or second cell
division after fertilization of an egg. Indeed, the
second division affords cells (blastomeres) for
which the echo of fertilization has been dissipated,
especially for totipotent sister blastomeres, e.g.,
mitotic echinoderm embryos (sea urchins or sand
dollars).
In this context, the process of cell reproduction
is neither a given nor simple. Indeed there are
many so-called checkpoints in the life of a cell—
checkpoints relying upon transcription, translation,
protein-protein interactions, post-translational
modification, or some combination of those. The
checkpoints provide a cell with the opportunity to,
in essence, pause and take stock of the state of
preparations before continuing its commitment to
progress through the cell cycle and mitosis, and
thereby reproduce itself.
Given that perspective, one can ask at what
point did the cell make the commitment to progress
through the cell cycle and reproduce itself? That
commitment is the product of a decision: to divide
or not to divide. That decision to divide represents
a fundamental step in biology, for which there are
the behaviors (e.g., component driven reactions and
regulation, etc.) and constraining external factors
(e.g., components, substrates, cofactors, internal
and external milieu, etc.).
The focus of my laboratory is one fundamental
question. How does a cell make a decision? We
study two basic decisions: (1) how the cell decides
to divide; and (2) how a macrophage decides
something it has encountered is dangerous and so
must be neutralized. We have found the decision to
divide by an undifferentiated cell (e.g., very early
blastomeres) has significant similarities to decisions
made by post-mitotic fully differentiated cells (e.g.,
macrophages).
In this article, I will focus on the process of
mitotic cell division and insights gained from
the study of mitotic cell division in eggs and
early embryos of echinoderms (e.g., sand
dollars, Echinaracnius parma, and sea urchins
Strongylocentrotus purpuratus and Lytechinus
pictus), and meiotic oocytes of mollusks (e.g.,
the surf clam, Spicula solidissima). I also include
a few notes about the people who helped get us
here. Among the experimental tools used by others
and me are analytical and quantitative multispectral light microscopy, quantitative picoliterscale direct pressure microinjection, correlative
transmission and scanning electron microscopy,
isolation, biophysical and kinetic characterization
and reconstitution of single and multi-enzyme
preparations, and a fair dose of good luck and
insights shared by and with colleagues and
teachers with whom I have had the pleasure of
studying for more than four-and-a-half decades.A
The history of cell division stretches back to
the late 1830s through early 1870s, accentuated
by detailed cytological studies of Schleiden and
Schwann;1 Strasburger2 with plant cells; and
Flemming,3 who provided the first descriptions of
mitotic cell division in animal cells (indeed, it was
Flemming who coined the term mitosis). These early
A There is much richness and detail in this story; in the
interest of a reader’s patience and page count, I will limit
this discussion to high points, and be happy to be more
expansive with those who have the interest.
FALL 2016
3
studies using brightfield light microscopes provided
clear demonstrations of what we now know to
be chromosomes, chromosome condensation
in mitosis and meiosis, the disruption of the
nuclear envelope, formation of the microtubuleand endomembrane-rich mitotic apparatus (the
functional and necessary combination of spindle
and asters), the microfilament-rich contractile
ring, formation of the phragmoplast in plant cells,
differential portioning of organelles within dividing
cells, and even the sub-micrometer dimensioned
centriolar pair at the mitotic pole. Their drawings,
prepared with pencil, pen and ink from careful,
direct observations of chemically fixed and stained
mitotic plant and animal cells using monocular
light microscopes (seemingly primitive by today’s
standards—with no fluorescent probes or confocal
or electron microscopes) were and remain
remarkable—by any standard. I have captured and
reproduced several of the historical images here.B
[Figures 1 and 2.] The key to these discoveries, as I
have learned from their writings (and my own
Figure 1: Mitotic progression, from prometaphase through
cytokinesis in aniline-stained animal cells, recorded
in pencil-pen-and-ink drawings by Walther Flemming
in his 1882 monograph titled: Zellsubstanz, Kern, und
Zelltheilung. (Leipzig: Vogel.) (1882).
Figure 2: Mitotic progression of the spindle apparatus,
B Dan Mazia, who, in August 1980, was afforded the
opportunity to look at some of Walther Flemming’s original
slides (circa 1896) told me of the stunning detail he was
able to observe in those slides of chemically fixed and
stained animal cells that Flemming had prepared about
a century before; he was humbled. My pre-World War
II brightfield light microscope, and even the half-scale
reproduction of Flemming’s light microscope that I was
presented by Zeiss about a quarter century later, as well
as my contemporary research microscopes, each show
remarkable detail on prepared slides of mitotic cells and
tissues; such is the window provided by fine optics.
4
from prometaphase through cytokinesis in aniline-stained
animal cells, recorded in pencil- pen-and-ink drawings
by Walther Flemming in his 1882 monograph titled:
Zellsubstanz, Kern, und Zelltheilung. (Leipzig: Vogel.);
Flemming coined the term “mitosis” and invented the
aniline staining technique, variants of which are still used
today.
had been to extend their studies from chemically
fixed and stained preparations to vital living
preparations. A pivotal step forward was the use of
cell culture techniques developed by Ross Harrison
in his studies of the development of neurons
and limbs in chick embryos, and description of
the apical epidermal ridge. The culture methods,
including his culture media, provided a new
platform for cell biologists and laid the foundation
for modern culturing of eukaryotic cells and tissues
(Harrison, 1907a, b, c).4, 5, 6
In this same era, Jacques Loeb, Otto Hertwig,
and others were focused on the process of
activation of eggs, both by fertilization and
so-called artificial activation, also known as
parthenogenesis (Loeb, 1913).7 At that time, the
questions were framed in fundamental biological
terms, while there was also a debate and
discussions in religious fora; indeed, Loeb’s 1913
compendium was found on the shelves of science
libraries of major universities and religion-focused
colleges, alike. Working separately (but in parallel),
Loeb and Hertwig were concerned with discovering
the mechanisms by which eggs were activated by
sperm at fertilization and the mechanism by which
fertilized eggs could prevent entry of additional
efforts), was careful
observation, staying true
to first principles, and
thinking with one’s eyes
and seeing with one’s
mind. These observations
are consistent with what
we know with modern
methods of observation
of living cells, and each
shows the presence of
particles (membrane
vesicles and reticula
of the endoplasmic
Figure 3: Detailed images of telophase mitosis in sea urchins. Left panel—mitosis
reticulum), which were
in the “green” sea urchin Echinus microtuberculatus (now known as Psammechinus
largely ignored by many
microtuberculatus) drawn by Boveri in 1900; right panel—an isolated mitotic apparatus
prominent workers in the from the purple sea urchin Strongylocentrotus purpuratus photographed by Mazia in
microtubule field.C [Figure 1960. Images captured and adapted from Figure 12 (page 130) of D. Mazia, Mitosis and
the Physiology of Cell Division, in J. Brachet and A. Mirsky (1961) The Cell – Biochemistry,
3] Let us look back as we Physiology, Morphology, Volume III – Meiosis and Mitosis, Academic Press, New York. This
prepare to look forward. right panel may be compared with the middle and lower panels of Figure 6 below.
These early studies
that largely focused on
sperm.8 Their straw man was the artificial activation
chemically fixed and stained preparations always
of eggs that could be accomplished by bathing
referenced observations of untreated living cells.
the eggs (e.g. of sea urchins, surf clams, and other
From there onward, a key goal of cell biologists
invertebrates) in various hypertonic solutions and
C Indeed, years ago one prominent “microtubule worker”
emphatically explained to me that “calcium was the dark
side of mitosis,” that the endomembranes (now known
to play an important role in cell regulation and stability
of microtubule-rich cytoskeletal structures) were “…
the dirt in the preparations,” and that “… it is clear that
microtubules control the cell cycle.” [To paraphrase A.N.
Whitehead: such is the fashionable opinion of those
choosing to disregard half the facts.]
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
solutions containing urea or cyanide. They observed
significant changes in cellular composition and
organization—not with electrophoretic gels, enzyme
assays, or polymerase chain reaction (as are
common today)—but with chemically fixed and
stained cells.
Among their findings (based upon observations
microscope of various manufacturers
is found in most laboratories utilizing
cell and tissue culture techniques for
their studies. In the post-World War
II period, with the popularity of the
phase contrast microscope and the
use of 16 mm ciné film and time-lapse
photography, new insights into dynamic
cellular processes were flooding cell
biology. In parallel, the use of linear
polarized light microscopes also began
to be developed (beyond novelty) and
used to significant advantage.
At approximately the same time,
Otto Warburg was extending his studies
Figure 4: Cytasters formed in sea urchin eggs parthenogenetically activated with hypertonic sea water by J. Loeb (circa 1903). Images
of metabolism to better understand
captured and adapted from: upper panel figure 331 (page 685) and lower panel figure 332 (page 686) of E.B. Wilson (1928) The Cell
rd
in Development and Heredity; 3 edition, MacMillan Publishing Company, New York; Reprinted 1987, Garland Press, Inc., New York. ISBN: and elucidate the mechanisms of
cancer, seen in part as uncontrolled
0-8240-1386-7.
cell division. Warburg found tumor
direct test. They injected solutions of calcium or
from experiments that Daniel Mazia and I
D
cells,
especially
those from solid tumors, had
ATP into muscle fibers and monitored the state of
performed, I lean more to Loeb’s work as being
a
propensity
to
metabolize
glucose through
contraction, and found the elevation of calcium
more extensive and readily reproducible), were
glycolysis
(and
thus
yield
lactic
acid), rather than
levels, and not ATP, triggered muscle contraction.
that depending on the means of activation, an
F
through
pyruvate
and
oxidative
phosphorylation.
Later, Daniel Mazia, while a student with
egg could: (a) produce numerous chromosomes,
This so-called “Warburg effect” fell out of favor
Heilbrunn in the mid- to late-1930s, showed there
(b) organize an aster as seen in mitotic cells
with the discovery of oncogenes and the role of
was a transient increase in intracellular (free)
with chromosome replication, (c) organize an
2+
accumulated genetic mutations in the emergence
calcium (Ca ) levels in eggs after fertilization.
aster and half of a mitotic spindle (half of a
and formation of tumors. The shift to largely
mitotic apparatus) with chromosome replication,
We now know from work largely performed in the
anaerobic metabolism by tumor and transformed
(d) organize numerous asters in the cytoplasm
past four decades that calcium ions acting in
cells is now seen as a consequence of these
(“cytasters”), (e) organize two half-mitotic
microdomains (which we demonstrated in mitotic
mutations. The observed Warburg effect results from
apparatus—which would appose one another—with
cells and the synaptic terminal) play vital roles
an accumulation of hexokinase 2 on the surface
condensed chromosomes between them, and (f)
in controlling motility, cytoskeletal structure and
of mitochondria in tumor and transformed cells
organize two half-mitotic apparatus—which would
organization, membrane fusions and remodeling,
through a selective binding to the mitochondrial
appose one another with condensed chromosomes
enzyme activities, and apoptosis. But how could
voltage-dependent anion channel;10 this is
between them – and undergo mitotic cell division,
one see detail within cells without chemical fixation
supported by the observation that tumor cell growth
and even produce swimming embryos (about 48
and staining, and thus avoid misleading artifacts
can be stopped by down-regulating glycolysis using
hours after activation). [Figure 4].
due to the chemical treatments?
3-bromopyruvate.11 This was also consistent with
Concurrently and through the mid-1950s, Lewis
The invention and introduction (in 1933) of the
the so-called Cori-cycle of integrated metabolism
V. Heilbrunn, a student of Loeb’s, determined
phase contrast microscope by Frits Zernike opened
of glucose and lactate between muscle (an
changes in cellular levels of free calcium were
living cells and tissues to direct observations of
uncommon site for tumor growth) and liver (a
associated with and likely responsible for numerous
dynamical processes; Zernike was awarded a
9, E
common site for tumor growth),12 i.e., that tumor
essential biological functions, e.g., amoeboid
Nobel Prize in 1953 for this invention. In 1942,
cell metabolism represents a cellular adaptation
movement (which we now know to be actin-myosin
Zeiss began production of the Zernike phase
to the tumor or transformed state. While thought
dependent), blood clotting, fertilization, muscle
contrast microscope. In 1943, Kurt Michel, a
to be consequential of accumulated mutations,
contraction, neuron transmission (excitability),
famous physicist and engineer at Zeiss, produced
alterations in metabolic machinery and output of
mitosis, and cytokinesis. There was much pushback
a now classic movie of mitosis that demonstrated
those pathways are integrated with the activation
on the notion of calcium as a regulator in biology
the powerful new phase contrast microscope. By
process.
from the biological sciences community, especially
1947, Caroline Bleeker and her life partner, G.J.D.J.
During World War II, a young undergraduate
from Albert Szent-Gyorgyi, who held that muscle
Willemse, had simplified the design to permit
student
named Shinya Inoué working in the
contraction was triggered by ATP (adenosine
mass production of phase contrast microscopes
laboratory
of Katsuma Dan (Tokyo University and
trisphosphate) and not calcium. Heilbrunn and
by her company, which allowed their use as a
Misaki
Marine
Biological Station) was studying
his long-time collaborator and colleague (and
common laboratory instrument to study unstained
the
process
of
mitosis with a homemade polarized
friend of mine) Floyd Wierczynski put this idea to a
cells and tissues. Today, the phase contrast light
light microscope. Inoué and Dan were trying to
D In 1979 and 1980 when I was a postdoctoral scientist,
Daniel Mazia and I replicated Loeb’s experiments
but recognized that we did not, at that time, have the
analytical tools needed to more deeply understand what
we were observing. We agreed that when I had the needed
tools, some of which I have developed in the intervening
years, I would resume those experiments, which is what we
are preparing to do.
E The initial response to phase contrast was
underwhelming; in 1932, Zernike brought his phase
contrast microscope produced with Caroline Bleeker to
Zeiss (Jena) to demonstrate its capabilities and hopefully
entice Zeiss to mass produce the microscope; the Zeiss
colleague’s (hubristic) response was, “If this had any
practical value, we would ourselves have invented it a long
time ago.”
F Interestingly, Warburg also demonstrated the rate of
respiration in sea urchin eggs increased significantly upon
fertilization, a parallel to Mazia’s observed increase in
intracellular free calcium levels upon fertilization, which
John Gilkey and George Reynolds imaged in fertilized sea
urchin eggs using the photoprotein aequorin in 1977
(long before now popular fluorescent calcium indicators).
FALL 2016
5
determine the nature of the fibers of the spindle
and asters of the mitotic apparatus and were
especially eager to learn the biophysical properties
of those fibers in living cells, i.e., without chemical
fixation or chemical staining. They sought to build
upon W.J. Schmidt’s initial work describing the
birefringent mitotic apparatus in dividing sea urchin
embryo cells.13 For this, Schmidt turned to polarized
light, reasoning that the fibers might exhibit intrinsic
birefringence, i.e., they would rotate polarized light
in directions relative to their long (length) or short
(diameter) axes.
Being wartime, supplies and resources were
scarce. Inoué concluded he needed to use
polarized light to probe the assembly processes
that gave rise to the spindle and astral fibers of the
mitotic cytoskeleton. He also realized that he would
have to build his own microscope.G Inoué located
a brightfield microscope with suitable lenses
and some calcite prisms to polarize and analyze
the light, but needed a stable stand on which to
mount all of the components. For this he found
and used a discarded machine gun barrel that
could serve as a stand for his lenses and prisms;
this assembly provided him with the mechanically
stable platform necessary for the high demands of
the sensitive polarized light methods he was using.
The assembly worked! With this new instrument,
Inoué obtained relatively clear images and got
some of the first biophysical measurements of the
retardation of birefringent spindle fibers—which we
now know are due to bundles of 25 nm diameter
assembled microtubules.H In his 1953 paper, Inoué
demonstrated that when mitotic cells were viewed
with a polarized light microscope, the fibers of the
mitotic spindle and asters were birefringent, labile,
and composed of proteins.14
By 1967, Inoué and Hidemi Sato were able to
show imposing biophysical manipulations on cells
would drive the assembly and disassembly state
of spindle and astral fibers (and other cytoskeletal
elements) from a pool of subunits. These
manipulations included alterations in temperature
and/or barometric pressure and the structure of
intracellular water as influenced by exposure to
D2O.15 Those subunits are now known to be tubulin,
and the environment within the mitotic apparatus
is kept at very low levels of free calcium ions, e.g.,
at or below 10-8 Molar by the action of intracellular
G Shinya came to be a teacher, colleague, collaborator,
and close friend of mine during the 30-plus years that I
studied and conducted research at the Marine Biological
Laboratory (Woods Hole, MA) and since.
H For this work, Inoué was awarded the title of
Rigakushi Zoology from the University of Tokyo in 1944.
He continued those studies as a graduate student at
Princeton, earning M.A. and Ph.D. degrees from Princeton
University in 1950 and 1951, respectively. At the age of
95, Inoué remains active in his science.
6
calcium-regulating endomembranes.16, I
Shortly after World War II, Inoué moved to
Princeton University and the Marine Biological
Laboratory (Woods Hole) to continue his studies
on the birefringent nature and properties of the
mitotic spindle in living cells. By the early- to mid1950s there was a significant debate within the cell
division community regarding the mechanism of
chromosome movement, and even the existence of
spindle and astral fibers as real, functional cellular
components. Two schools of thought prevailed: One
held that the spindle and astral fibers were artifacts
of chemical fixation and staining—and not natural
components of cells. An adherent to this first notion
was Ethel Browne Harvey, an embryologist with a
keen focus on cell division, who felt the spindle
fibers were fixation artifacts.J Harvey extended
Loeb’s observations on parthenogenesis of eggs
with her remarkable finding that enucleated eggs
could be stimulated to develop into multicellular
organisms without chromosomes: “…non-nucleate
organism lacks chromosomes, genes and therefore
the hereditary qualities usually associated with
the nucleus.”18 [Figure 5] Adherents to the second
school of thought felt the spindle fibers were real
cellular structures—and not artifacts of chemical
fixation. How to resolve this controversy—and
expand our understandings?
At the 1953 General Scientific meetings of the
Marine Biological Laboratory (Woods Hole, MA),
Inoué presented black-and-white 16mm ciné
(movies) showing the birefringent mitotic apparatus
appearing and functioning during cell division
of early sea urchin embryos observed using his
polarizing light microscope. At one point, Harvey
spoke up saying that all of what Inoué was showing
was artifact and perhaps some trick because
the cells had to have been chemically fixed; the
auditorium hushed. Shinya calmly replied, “But the
cell divided!” At that moment, the question was
I We were able to establish that value using highly
engineered isoforms of aequorin prepared and
provided by Osamu Shimomura and a photon-counting
multispectral video light microscope system that I
designed and built, as reported that in several studies
using mitotic cells (e.g., Reference 17) and squid axons
(e.g., Llinás, R., Sugimori, M., Silver, R.B. (1992) Science.
256:677-679.).
J Harvey made several pivotal observations in her career.
One was the demonstration of an “organizing center”
capable of re-directing cell and tissue differentiation. This
finding was made 15 years before the studies of Hans
Spemann and Hilda Mangold – for which he alone was
awarded a Nobel Prize in 1935 (Mangold died in 1924
from burns after the explosion of a kitchen gasoline-fueled
heater and subsequent fire; a Nobel Prize is not awarded
posthumously). Browne-Harvey had sent a copy of her
1909 paper to Spemann with the handwritten annotation:
“Complements of E.N. Browne.” Spemann received and
read and annotated the paper reprint, but did not in turn
acknowledge that work in his own works, including his
studies co-authored with Hilde Mangold. It is clear that
most biologists of the time did not appreciate or recognize
the significance of her findings; science and the scientific
community were not yet ready for such a finding.
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
Figure 5: Ethyl Harvey’s observations of
parthenogenetically activated merogones, i.e., eggs from
which the female pronuclei have been removed before
activation. Harvey found such eggs proceed with evident
cell cycle changes in cytoskeleton, mitotic cell division,
and ultimately hatching of anucleate cells. Her images
are camera lucida drawings of non-nucleate egg fractions
(parthenogenetic merogones) from the Atlantic purple sea
urchin Arbacia puntulata. The coarse stippling denotes
yolk granules, the large solid dots denote pigment. (The
times given are times after activation and return to sea
water.).” Figure captured and adapted, and legend text
captured from: E.B. Harvey (1936) Parthenogenetic
Merogony or Cleavage, without Nuclei in Arbacia
punctulata. Biol. Bulletin, 71:101-121.
resolved, and the explanation was accepted by
all present; the paper that followed demonstrated
spindle and astral fibers were real, dynamic
components of cells— and the dynamics were an
essential component of the mitotic process.17 We
now know these fibers are bundles of microtubules,
and that they are dynamic—as Inoué had suggested
and demonstrated (all of this was long before the
use of fluorescent markers and invention and use of
confocal microscopes).
In 1952, Daniel Mazia and Katsuma Dan
reported they had succeeded in isolating intact
mitotic apparatus from first cell cycle metaphase
sea urchin embryos using solutions containing
hexylene glycol.18 Their phase contrast microscope
images were consistent with the chemically fixed
and stained preparations of earlier studies, with
the added anticipated benefit of allowing the
determination of the motors and mechanisms
of chromosome movement. Subsequent studies
from many laboratories showed that those
preparations could not support chromosome
movement and that their preparations had two
major protein components resolved with analytical
ultracentrifugation: proteins that sedimented with
values of 22S (Svedbergs) and 6S. Subsequent
analyses demonstrated the major protein at 22S was
yolk protein—and not part of the mitotic machinery,
while the minor component at 6S turned out to be
tubulin. The exposure of the cells to hexylene glycol
stabilized the cytoskeletal elements to an extent
they were incapable of assembly-disassembly or of
supporting chromosome movement as seen during
prometaphase or anaphase. By perturbing cells with
agents that cause microtubules to disassemble (e.g.,
colchicine or high hydrostatic pressure) or assemble
beyond that which is normally observed (e.g., D2O),
Inoué observed spindle fibers are in a state of rapid
dynamic equilibrium with a pool of soluble subunits
(including tubulin) in the cytoplasm.
He went on to show assembly and disassembly of
spindle fibers experimentally induced by biophysical
means can generate forces within the cell, and he
proposed mitotic chromosomes movements are the
result of such forces. These ideas were summarized
in a seminal review he co-authored with Hidemi
Sato.19 The assembly-disassembly mechanisms for
microtubules are now generally thought to provide
the physical force for driving chromosome movement,
e.g., to arrive at the metaphase plate and then
make their poleward movements during anaphase.
K
From parallel studies of various motile systems,
Inoué posited that force generation by assemblydisassembly of cytoskeletal protein fibers (via their
subunits) is likely the most ancient of cellular motile
mechanisms in eukaryotic and prokaryotic cells.
Several laboratories turned their attention
to isolating a functional mitotic apparatus, i.e.,
one that could initiate-and-sustain or sustain
ongoing anaphase chromosome movement.
Various approaches were taken using isolation
milieu containing alcohols, glycols, detergents
or combinations of those. While the isolated
structures appeared similar to what was sketched by
Flemming and others, none initiated chromosome
movement, and only one could sustain chromosome
movement—when the plasma membrane was
permiabilized with detergents. Patricia Harris
and Peter Hepler separately presented electron
micrographs of elements (endomembranes) of
the endoplasmic reticula of sea urchin (Harris20)
and plant cells (Hepler21); they suggested these
endomembranes served to regulate local calcium
levels and were therefore likely important for
assembly and functioning of the mitotic apparatus.
Their work was largely dismissed by those focused
on the assembly properties of brain microtubules
as a window to mitotic chromosome movement
and mitosis itself. It is at this point (fall 1977) that
K The mechanism and process are commonly referred to
as polymerization and depolymerization, although there
is no evidence for covalent bond formation or breakage
during the addition or removal of microtubule subunits.
This author continues to refer to the assembly and
disassembly of the components of microtubules.
I migrated from studying the structure-function
properties of the contractile unit of muscle and the
protein chemistry of myosin and actin to the study of
cell division.
As a postdoctoral scientist in a protein chemistry
laboratory, that of R. David Cole at the University of
California at Berkeley, I posed the question of how
cells accomplished an asymmetric apportionment
of non-chromosomal components that gave rise to
sister blastomeres having different developmental
fates in early embryos. To achieve this, I felt I would
have to isolate mitotic apparatus (MA) that appeared
in the test tube as they did in an intact cell. I soon
achieved this goal, and can remember the chill
I felt as I saw isolated mitotic apparatus tumble
across the field of view of the phase contrast light
microscope that I was using in Cole’s cell culture
room.
The MA was now a real 3-dimensional structure
Figure 6: Top panel: Mitotic apparatus as recorded in
a pencil-pen-and-ink drawing by W. Fleming in his 1882
monograph: Zellsubstanz, Kern und Zelltheilung. (Leipzig:
Vogel. 1882). Flemming correctly predicted that the vesicles
were hollow as first shown with electron microscopy by G.
Palade and K. Porter in 1954 (e.g., Plates 55-62). Middle
panel labeled “A”: An isolated native mitotic apparatus
imaged with differential interference contrast (DIC) optics;
Bottom panel labeled “B”: A critical point dried isolated
native mitotic apparatus imaged with a field emission
scanning electron microscope. The bar represents 10 µm.
Panels “A” and “B” from Silver, R.B., Cole, R.D., and Cande,
W.Z. (1980) Isolation of mitotic apparatus containing
vesicles with calcium sequestration activity. Cell 19: 505516.
in my eyes—and not just a projection in my mind.
Those MA, isolated from metaphase sea urchin
embryos, showed the characteristic astral and
spindle fibers that Flemming recorded in 1882
[e.g., Figures 1 and 2], 95 years earlier, but also
had particles of various optical densities. Could
these be the vesicles and reticula, akin to what
Flemming and others saw in MA of living cell [e.g.,
Figures 6]? I looked up and saw a small water
bottle and with it carefully added a drop of water
to the suspension of tumbling MA. Immediately,
many of the particles swelled as spheres to many
times their original diameters; they were osmotically
active! I sat transfixed for several minutes as I
watched the vesicles swelling, and some even pop
when they touched an astral fiber of another MA. I
realized, at that moment, that my research direction
had to change; I went to the lab telephone and
called the Radiation Safety Office to order 45Ca
to test if these vesicles could sequester calcium
in an ATP-dependent fashion.L In two days, once
the 45Ca was in hand, I ran the assay—the results
of which showed that the endomembranes could
sequester calcium in an ATP-dependent fashion. In
subsequent experiments, I was able to show that:
· Sequestration had to be from endoplasmic
reticula and not mitochondria;
· Calcium-uptake activity was accomplished by
a Ca-dependent ATP-dependent membrane
protein that shared epitopic homology with the
calcium-pump of sarcoplasmic reticulum;
· The pump enzyme and its activity were
necessary for maintenance of the MA in vivo;
· The cells required a transient calcium
signal from endomembrane stores before
nuclear envelope breakdown (NEB) (i.e., one
could stop, or stop and re-start mitosis by
manipulating that calcium signal);
· Cells actually generate a peri-nuclear prenuclear envelope breakdown calcium signal
from intracellular stores;
· Those signals occur in microdomains, which
we imaged in dividing cells, and, with Llinás
and Sugimori, at the synaptic pre-terminal of
neuromuscular junctions;
· Those signals had a defined space-time
frequency—which meant that they were digital
and not analog;
· The signal is triggered by a timed generation
of the bioactive lipid leukotriene B4 (a
derivative of arachidonic acid), that the MA
endomembranes also had an array of enzyme
L The Radiation Safety Office was familiar with me and
practices from experiments I conducted as a graduate
student, also at Berkeley. After a brief conversation, they
agreed to order the 45Ca and told me that they were going
to amend David Cole’s radiation license to accommodate
my experiments. I then went to see David, and told him
that we were amending his license, to which he replied:
“I know that you will tell me what it is about once you run
experiment” —which I did; the results of which were to our
mutual delight.
FALL 2016
7
activities that included phospholipase A2
through 5-lipoxygenase and Lt-A4 hydrolase, the
pentose phosphate pathway, the glutathione
red-ox pathway, and glycolysis; and,
· With mathematical models of this suite of
enzymes, we could show through data-driven
modeling that highly precise pulsatile calcium
signals could readily be generated.
These were significant departures from what was
assumed from studies of brain microtubules, but
consistent with the works of those whom I have
noted above, and others.22 In other experiments,
we found: (a) that we could initiate developmental
processes by exposure of unfertilized eggs to
inhibitors of both protein or DNA synthesis, and (b)
that similar properties regarding calcium control
and enzyme networks are inherent in a stationary
macrophage that I discovered in toadfish.M
Now, we are poised to pose the same questions
of activated eggs and merogones as described by
Loeb and Harvey, as noted above, using modern
methods. Taken together, the work of Loeb and
Harvey, with subsequent findings of Hunt and
me,23 lead us to a different appreciation of
eggs and the decisions to divide and develop:
M We (Garrett Liddil and I) are analyzing the primary
sequence of a membrane receptor in those fish that
impacts a dramatic difference in the physiology of
toadfish from multiple geographic locations. The open
reading frame of that receptor is about 1,500 bases; the
solution to these sequences will allow us to correct a
species misidentification connected to this department
from 1896.
Cited References:
1
2
3
4
5
6
7
8
Schwann, M.J. and Schleiden, T. (1839) in “Schwann
and Schleiden’s Researches.” Syndenham Society,
London, 1847. English translation by H. Smith.
Strasburger, E. (1913) Zellen- und gewebelehre,
morphologie und entwicklungsgeschichte; Leipzig
[etc.] B. G. Teubner; captured from: https://archive.
org/details/zellenundgewebel1913stra
Flemming, W. (1879) Arch mikr. Anat. 16:302436.; Flemming, W. (1882) Zellsubstanz, Kern, und
Zelltheilung. [Cytoplasm, Nucleus and Cell Division.]
(Leipzig: Vogel.)
Harrison, R.G. (1907a) J. Exp. Zool., 4:239-281.
Harrison, R.G. (1907b) Anat. Rec, 1:116-118
Harrison, R.G. (1907c) Proc. Soc. Exp. Biol. and Med.,
4:140-143.
Loeb, J. (1913) Artificial Parthenogenesis and
Fertilization. Translated from the original in German by
W.D.R. King. The University of Chicago Press, Chicago,
Illinois.
Clearly, eggs are primed to divide—needing only a
physiochemical signal, and halting of processes
sensitive to inhibitors of protein and DNA synthesis
in a quiescent egg, to initiate that complex
process. And as Harvey elegantly demonstrated,
the chromosomes per se are not essential for
that decision and early mitotic processing—and
perhaps not taking an active role in cytological
reorganizations and mitosis itself. With that
background and the perspectives of Loeb, Harvey
and others in mind, among the questions we are
about to ask the cells are:
· Do the asters and forms of MA in activated
eggs and merogones exhibit ATP-dependent
calcium uptake activities as observed in mitotic
cells from fertilized eggs?
· Do activated eggs and merogones generate
regular, digital calcium signals within
microdomains?
· Do the asters and forms of MA in activated
eggs and merogones exhibit the same or
different enzyme networks as observed in
mitotic cells from fertilized eggs?
· Are the nuclear chromosomes unnecessary
for early cytoplasmic cycling, as suggested
by Harvey’s experiments, and thus, when is
chromosomal information needed?
· What new insights into these signals and their
generation can be attained through faithful
mathematical modeling of enzyme networks—
using a new form of enzyme agent that
accommodates the various statistical variations
inherent in enzymes (as we step away from
Michaelis-Menten kinetics) in the complex
environment of the intracellular environment?N
We also seek to learn if we can develop a
productive fusion of in-line computational analysis
of multispectral microscopy with kinetic simulations
to bring the wet and dry lines of experiments
together. Through this approach, we hope to gain
deeper insights into the process of how cells make
decisions.
As biologists, we understand that much insight
can be gained from studying the basic fundamental
principles attendant to foundational processes
such as mitotic cell division, but also from studying
variations on the foundational process. In all cases,
clear unbiased observations are essential to the
process that we call science. Much of the activity
guided and inspired by the faculty and students in
this department of biology employ such powerful
approaches to understanding cells. I relish the
opportunities to continue in these studies of the
past 4½ decades, and to help train the coming
generation of young scientists and scholars.
8
9
15 Inoué, S. and Sato, H. (1967) J. Gen. Physiol. 50:
259–292. doi:10.1085/jgp.50.6.259.
16 Silver, RB. (1996) Cell Calcium. 20:161-179.
17 Inoué, S. (1953) Chromosoma 5:487–500.
doi:10.1007/bf01271498.
18 Mazia, D. and Dan, K. (1952) Proc. Nat. Acad. Sci.
USA 38:826-838.
19 Inoué, S. and Sato, H. (1967) J. Gen. Physiol. 50:
259–292. doi:10.1085/jgp.50.6.259.
20 Harris, P. (1975) Exp. Cell Res. 94:409-425; Harris, P.
(1982) J. Cell Biol. 14:475-489.
21 E.g.: Hepler, PK. (1977). in Mechanisms and Control
of Cell Division, T. L. Rost and E. M. Gifford. Jr., eds.
(Stroudsburg. Pennsylvania: Dowden, Hutchinson and
Ross) pp. 212-222.
22 E.g.: Alkon, DL and Rasmussen, H. (1989) Science,
239:998-1005.
23 Hunt, T. and Silver, RB. (1985). Biolog Bull. 169:542.
10
11
12
13
14
Loeb, J. (1915) Amer. Nat. 581:257-285.
Zernike, F. (1953) How I discovered phase contrast.
Nobel Lecture. Available at: http://www.nobelprize.
org/nobel_prizes/physics/laureates/1953/zernikelecture.pdf
Bustamante, E. and Pedersen, P.L. (1977) Proc Natl
Acad Sci USA, 74:3735-; Bustamante E, Morris, H.P.
and Pedersen, P.L. (1981) J Biol Chem, 256:86998704, PMID: 7263678; Mathupala, S.P., Ko, Y.H., and
Pedersen, P.L. (2009) Semin. Cancer Biol 19:17-24;
PMID: 19101634;
Pederson, P.L. (2008) J Bioenerg Biomembr, 40:123126, PMID: 18780167.
Cori, G.T. and Cori, C.F. (1952) J Biol Chem, 199:661667, PMID: 13022673.
Schmidt, WJ. (1937) Protoplasma Monographien, Vol.
11. Berlin: Gebruder Borntrager; Schmidt, WJ. (1939)
Chromosoma 1:253–264.
Inoué, S. (1953) Chromosoma 5: 487–500.
doi:10.1007/bf01271498.
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
N We continue a long-term effort begun in 1985 and
while I was at Argonne to develop a statistically-oriented
numerical agent to more accurately model enzyme
activities and agent-based enzyme networks empirically
identified in dividing cells and macrophages to provide
more accurate simulations of controlling enzyme networks
in cell decisions.
FACULTY PROFILE
Katharine “Kate” Lewis
Have you ever wondered how you came to have a nose in the middle of your face or four
fingers and a thumb on your hand? How it is that while we are all unique most of us are
born with the same basic body plan. We have toes on our feet and fingers on our hands,
rather than fingers on our feet for example. Two eyes form at the top of our face and a
mouth at the bottom.
H
ow do cells in a growing embryo know
how to make different body parts and how
are these made in the correct places and
at the correct times? These and similar
questions have fascinated me throughout my
scientific career. These questions are the focus of
a branch of biology called developmental biology,
and as a geneticist my research has concentrated
on the roles that different genes play in these
processes.
I am still surprised that I ended up as a biology
professor. I didn’t study any biology at secondary
school (equivalent to middle and high school
in London, England, where I grew up). Even in
general science classes I was taught by a physicist
who himself knew so little biology, he had to go
next door to check with one of the other science
teachers how many legs an insect had.
Having said that, my interest in scientific research
and travel—the two things that in the end brought
me to SU—started relatively early as a result of my
decision to take a “year off” or “gap year” between
secondary school and college. I was lucky enough
to obtain a research job with Imperial Chemical
Industries (ICI), a big chemical and pharmaceuticals
company. I worked in a research department that
was developing a technique called small angle
scattering to analyze their various products such
as different paint samples. My job included both
theoretical and experimental research. I wrote and
improved computer models to calculate particle size
and shape from small angle scattering data and
participated, as part of a team, in experiments on
real samples.
This was my first experience with having to work
around the specific time constraints of a particular
experiment. We used two different external largescale facilities on which we would buy “beam time.”
On one we would run 24-hour experiments and
have to be there constantly throughout that period.
On the other – we would run 72-hour experiments,
taking turns working shifts and sleeping at a hotel
in between.
These experiences resulted in my first scientific
paper. They also enabled me to earn and save
sufficient money to travel through Pakistan,
India, and Nepal at the end of the year.
While I had travelled abroad before with my
family (to France) and my school band and
youth orchestra (to Europe, the USSR, and
the USA), this was my first independent
overseas experience and it confirmed that I
had the travel bug.
I joined an organized overland trip and had an
amazing time and lots of adventures, including
almost venturing into Afghanistan by mistake (we
took a wrong turn and luckily were stopped by a
village of Afghan refugees who gave us tea and sent
us back the right way), and being in Islamabad
when the
Pakistan Prime
Minister Benazir
Bhutto was
deposed. I heard
the news while
sitting in a tent
listening to the
Kate at tea in Afghan refugee
village near the Afghan border with world service on
Pakistan.
a little shortwave
radio. I think we
probably knew before many Pakistani citizens did.
For my first degree I studied Natural Sciences
at Cambridge University. At Cambridge all students
are also attached to a college and I chose to
apply to King’s College. For anyone that has visited
Cambridge, this is the college with the very famous
large chapel, the building of which was started
by Henry VI (who also founded the college) and
completed by Henry VIII.
King’s also has a strong association with the
Bloomsbury group as Maynard Keynes was bursar
for several years, Roger Fry and E.M. Forster
were both fellows, and several other Bloomsbury
members were regular visitors (King’s is the male
college with the fine food discussed in Virginia
Wolf’s A room of one’s own). Alan Turing was also
a fellow at King’s—explaining why the college
computer room was called the “Turing Room.”
As with many ancient institutions, King’s has a
slightly schizophrenic reputation in current times.
For example, it still has a very traditional male
only chapel choir, world famous particularly for its
Christmas Eve service of nine lessons and carols,
that is broadcast live around the world on the BBC
world service. King’s also has explicit links with Eton
college, which was cofounded by Henry VI, and is
probably the most famous private fee-paying school
open source
HOW DOES THIS HAPPEN?
View of King’s College Cambridge front gate and chapel.
FALL 2016
9
to undertake research projects as it
is here in the US. Usually, the only
opportunity is in the final year of study
and often this is just a small part-time
project undertaken for one semester. I
was fortunate to also have a summer
research experience, funded by the
Nuffield Foundation, where I looked
at the expression of genes located in
the region of chromosome 23 that is
present in three copies in individuals
with Down Syndrome. Our hope was
that this would provide greater insight
into the phenotypes associated with
this syndrome.
For my final, third-year research
project I worked with Michael
Ashburner, a prominent Drosophila
geneticist. I tested whether a couple
of synthetic compounds could mimic
the effects of a hormone called
ecdysone. The latter is important
for metamorphosis of insects
including flies, and in Drosophila
larvae it causes several genes to
turn on. This effect can be observed
microscopically because in some
tissues of the larvae there are giant
Punting with other King’s College undergraduate scientists.
chromosomes called “polytene”
chromosomes, and in these chromosomes you can
in the UK, and yet King’s is widely considered the
see the bits of the DNA that are being turned on
most left-wing of the Cambridge colleges. King’s
expand (a phenomenon referred to as “polytene
was one of the first three male-only colleges to
chromosome puffing”). So basically my research
admit women students and fellows. It pioneered
project consisted of soaking maggots in a chemical
recruitment of students from state-run high schools
and then pulling their heads off and looking down
(as opposed to private fee-paying schools) and, at
the microscope to see if I could see enlarged bands
least while I was there, the student body eschewed
on the giant chromosomes from the salivary glands.
many of the traditional Cambridge trappings and
During my final year of undergraduate studies
traditions, like wearing academic robes for formal
I decided I wanted to continue with research
dinners and summer balls.
and study for a Ph.D. However, when applications
Natural Sciences is the only “major” for studying
for Ph.D. places were due at the end of the fall
science at Cambridge and it includes all of the
semester, I did not yet know what I most wanted
life and physical sciences. Students choose three
to study. Therefore, I decided to take another “gap
subjects in their first year (plus math) and then
year” and I applied for fellowships to go to the
gradually specialize until they are studying just
United States for a year.
one subject in their final year. This enabled me
I was fortunate to receive a Kennedy Memorial
to choose a biology class that didn’t require any
Fellowship for one year of study at Harvard. The
previous knowledge of biology called “Biology of
Kennedy Memorial Fellowships were created in
Cells” in my first year as well as chemistry and
memory of President John F. Kennedy. When he was
physics.
assassinated, people in the UK donated money and
By my second year I had decided I was more
a foundation was created. This foundation sends
interested in chemistry than physics so I carried
between 8-12 people a year to either Harvard or
on with chemistry and was awarded a studentship
MIT. This wasn’t my first visit to the US as I had
by ICI. However, I had enjoyed Biology of Cells
travelled with my high school band to the U.S.
so much I also continued with the next class
However, this was the first time that I lived in the
in that sequence: Molecular Biology. In both of
U.S. and was the start of my trans-Atlantic hopping.
these biology classes I was most fascinated by
I lived in Harvard graduate housing. Friends
developmental biology and genetics and in the end,
back home couldn’t believe that this was located
for my final year, I chose to study genetics, including
on Oxford Street, in Cambridge. For me it was
the genetics related to developmental biology.
a magical year. I remember constantly reading,
It isn’t as usual in the UK for undergraduates
10
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
eating on the run, playing card games in the pub
on Sunday evenings with other Kennedy scholars
because we would always forget about the
Massachusetts ban on buying alcohol on Sundays,
and frequenting discount book stores late at night
(I shipped home three full mail sacks of books and
lecture notes at the end of the year).
I didn’t study any science during this year but
instead took the opportunity to broaden my studies
into literature, philosophy of science, psychology,
and women’s studies. I also experienced more snow
that I had ever seen before (Cambridge and Boston
had a record snow fall that year– although that
record has been surpassed several times since).
I didn’t have to shovel as I was living in Harvard
housing, but I did get to walk through the corridors
that were cut into the snow across Harvard yard,
with snow towering above me on either side. It was
the closest to being snowed in that I had ever been
at that point. Although since I’ve moved to Syracuse
I’ve seen snow on a whole different scale.
Before leaving for Harvard, I had arranged a
Ph.D. position for my return. This was at Imperial
Cancer Research Fund (ICRF, now called Cancer
Research UK) in London working with Philip Ingham,
a developmental geneticist who had traditionally
worked with Drosophila but was starting to work
with zebrafish.
I was still fascinated with developmental biology
and genetics and had really enjoyed learning about
the pioneering Drosophila research in these fields,
but I was attracted by the prospect of working on a
new organism. Zebrafish offered the allure of similar
genetic techniques to Drosophila but in a new
vertebrate model system about which much was
still unknown.
Figure 4: Zebrafish grow incredibly fast. The are
born as eggs inside a clear egg shell called a
chorion. By 1-2 days they already look like little
fish, they hatch when just a few days old, and are
sexually mature by 3 months.
I was not alone in being excited by the potential
of this new research animal. Many established
Drosophila researchers either expanded into also
using zebrafish (like my Ph.D. advisor) or switched
almost completely (like the Nobel prize-winner
Christiane Nüsslein-Volhard).
For my Ph.D. research, I studied a pathway
that had just been identified in vertebrates by
an international collaboration between my Ph.D.
advisor and two professors at Harvard, Andy
McMahon and Cliff Tabin. This was the Hedgehog
pathway.
The hedgehog gene had already been identified
as being crucial for correct embryonic development
in Drosophila, and these three labs decided to
test whether this gene also existed in vertebrates.
At the time, very few genes had been shown to
be conserved between invertebrates such as flies
and vertebrates such as fish, birds and mammals.
Thus, hedgehog was one of the first of what would
become many examples of genes important to
fly development we know now are also crucial for
vertebrate, including human, development.
The hedgehog gene encodes for a signaling
protein, and my job was to see if the receptor for
this signal, a protein encoded by a gene called
patched, was also present in vertebrates. Working
with a postdoctoral fellow Jean-Paul Concordet
for the first year and then by myself, I was able to
show not only was patched present in zebrafish but
there were two such genes. We analyzed how these
genes were regulated by Hedgehog signaling and
I also identified and characterized several mutant
zebrafish lines that affected the functions of the
Hedgehog pathway.
I was awarded an EMBO short-term fellowship to
go to Tübingen in Germany, where there had been a
large-scale screen, directed by Christiane NüssleinVolhard, looking for mutations in the zebrafish
genome that produced embryonic phenotypes.
This fellowship enabled me to screen through the
Tübingen mutant collection for mutants that looked
like they might affect Hedgehog signaling. I then
went on to prove that the mutations I identified did
indeed disturb Hedgehog signaling, and through
analyzing the phenotypes of the mutations I was
able to show that Hedgehog signaling plays crucial
roles in correct muscle development.
The ICRF was not a university and hence could
not award degrees. Therefore, to obtain my Ph.D., I
had to also be affiliated with a university and have
a university advisor. I was very lucky that Professor
Cheryll Tickle at University College London (UCL)
agreed to be that advisor. Usually a university
advisor just met with students once a year to check
on progress and sign forms, but I was fortunate to
spend time in Professor Tickle’s lab and conduct
experiments and write papers with her. This initially
occurred because her lab published a paper
describing a chicken mutation called talpid3.
While I had identified several zebrafish mutants
that affected the Hedgehog pathway, I had not yet
identified any that had the phenotype I would have
predicted for a patched mutant. Talpid3 looked
Dr. Lewis examining zebrafish embryos with Solvay High School students
like it might be the chicken version of that elusive
mutant. I talked to Cheryll about this and she
invited me to work on the mutant. In collaboration
with one of her graduate students, I was able to
show talpid3 was indeed in the Hedgehog pathway,
although the gene involved was not identified until
several years later (and did not turn out to be
patched).
Sustaining mutant chicken lines is not an easy
business. The talpid3 mutant line was maintained at
the Roslyn Institute in Edinburgh (the same place
that would later create Dolly the sheep) and just
after I obtained my first really exciting result, the
line was almost lost, and we were unable to obtain
any more embryos for a year.
When we finally were able to get more eggs
from this line I fetched them myself by hand, so
precious were they. Bringing them back to London
on the train I caused some consternation. The
eggs were carefully wrapped in a big box on the
luggage rack to keep them at a relatively constant
temperature and hopefully keep them safe. Every
time someone would add a suitcase to the rack I
would say, “Please be careful, I have eggs in there”.
When someone finally asked me why I was bringing
eggs from Scotland to London and why I couldn’t
just buy some when I got to my destination, without
thinking I replied, “Because they are special mutant
eggs,” and I got some very strange looks.
Through studying the talpid3 mutation and
also other components of the Hedgehog pathway,
we were able to make significant progress in
understanding how Hedgehog signaling patterns
the developing limbs of vertebrate embryos—in
particular the identity and organization of the digits.
While I enjoyed my Ph.D. studies, I found
I missed some of the other studies and the
reading that I had started at Harvard. Therefore,
during the second and third years of my graduate
studies I took evening classes at a local university,
Westminster University, and studied for an M.A. in
women’s studies.
This provided some balance in my life. When
experiments weren’t working, my studies for the
M.A. degree were usually going well. It was a good
way to forget about the Ph.D. for a few hours a
week, engross myself in other ideas and ways of
thinking, and it also introduced me to a great new
set of friends. It also gave me a good theoretical
base for my thoughts and opinions about feminism,
diversity, and equality.
For my postdoctoral training I knew I wanted to
continue working on developmental genetics and
using zebrafish. I decided to apply to labs in the
U.S. and ended up with a hard decision between
New York City, Seattle, and Eugene, Oregon. I
decided in the end to go to Eugene because of the
depth and strength of the zebrafish research there
(Eugene is where zebrafish research started), and
because I was interested to find out if I would like
living in a smaller town rather than a city. I obtained
a Wellcome Trust Fellowship from the UK to join the
lab of Professor Judith Eisen at the University of
Oregon and ventured across the Atlantic to live for
the second time.
For my postdoctoral research I initially continued
studying the Hedgehog pathway, this time
concentrating on its roles in making the nervous
system. I then expanded into looking at other
pathways and processes that are important for making
motoneurons (motor neurons), which are the nerve
cells that communicate with muscles and control
movements. I also taught undergraduates for the first
time, performing guest lectures for my postdoctoral
advisor and organizing and teaching a women’s
studies summer class based on my M.A. research.
FALL 2016
11
These experiences confirmed for me that I really
enjoyed (and still enjoy) teaching, and as a result
I have sought out faculty positions in university
biology departments rather than medical schools.
I find teaching provides a positive balance with
scientific research, because the satisfaction
obtained from teaching is more immediate than the
more long-term rewards from research.
The University of Oregon had a great teaching
effectiveness program, where I was able to take
workshops and classes on everything from teaching
large classes to diversity in the classroom, and a
strong human resources training program through
which I was able to take an in depth course on
supervising and managing others. I’ve been grateful
ever since for these opportunities because while
teaching and managing a research team are crucial
components of most professorial jobs, we are not
usually given any instruction or guidance on how to
teach, mentor, or manage other people.
Academic appointments in the United Kingdom
are advertised and awarded on a very different
timetable to those in the States. Here the process
usually begins a year before the start date for the
position. In the United Kingdom, jobs are usually
advertised just a few months before. However, for
young scientists starting out in their first faculty
position there is an additional option of careerdevelopment fellowships in the United Kingdom,
and these are advertised at least a year before.
These fellowships have the advantages that they
do not carry the same teaching load and are
prestigious to obtain, mainly because they are
highly competitive, but have the disadvantage
that they are temporary appointments (you are
effectively generating your own salary through grant
funds, also known as “soft money”).
I was fortunate to obtain a Royal Society
University Research Fellowship to return to the UK
and set up my first research lab. This fellowship
supplied my salary and a small amount of money
for experimental reagents. I joined the Department
of Anatomy, which later became the Department
of Physiology, Development and Neuroscience, at
Cambridge University in January 2004, and I also
returned to King’s College as a fellow.
In the anatomy department, I started my own
research lab, still working mainly with zebrafish.
During my postdoc I had realized that while we had
learnt a lot about how motoneurons are made as
embryos grow, most of the nerve cells in the central
nervous system are interneurons, nerve cells which
gather and process information within the central
nervous system (CNS) and pass that information
on to other nerve cells.
Little was known about how different types of
interneurons are made, because historically they
have been less studied than other nerve cells. I
decided it was important to try and fill this gap in
our knowledge, both to help us understand how
12
Figure 5: The Lewis lab routinely labels zebrafish nerve cells with fluorescent proteins. Examples of different
photographs of labeled nerve cells in live embryos. On the left is an 18-hour-old zebrafish embryos
indicating in red the approximate region where the labeled nerve cells were observed.
the central nervous system forms and functions,
but also so better therapies can be developed for
people whose spinal cords or brains have been
damaged by injury, disease, or neurodegeneration.
I decided to make interneuron specification—and
in particular the question of how different types of
interneurons are made in the spinal cord—the main
research focus of my lab.
While at Cambridge, my lab made some
important discoveries about several different types
of interneurons that form part of locomoter circuitry
in the spinal cord. We identified important genes
expressed by several of the nerve cells involved in
this circuitry and showed that a particular family of
genes was important for instructing several different
classes of spinal cord nerve cells to become
inhibitory (use a chemical messenger than inhibits
the electrical activity of the cells with which they
form contacts).
In the main, nerve cells are made in very
similar ways in the zebrafish spinal cord as in the
mammalian spinal cord. Most of the genes involved
in specifying distinct types of nerve cells are highly
conserved between different vertebrates. However,
we discovered one class of regulatory genes that
seemed to behave a little differently in zebrafish
spinal cord compared to mouse. This inspired me
to investigate how this family of genes and other
highly related families of genes have evolved in
vertebrates, and we collaborated with another lab
in London to answer these questions and also
branched out into some experiments on frogs and
sharks.
In addition, through serendipity, we investigated
the functions of a gene called evx1 in joint
formation in zebrafish fins. This project came
about because one of my graduate students, Claus
Schulte, noticed zebrafish with two copies of a
mutant evx1 gene had raggedy looking fins. He was
able to show that this was because these mutants
did not form joints in the long bony-rays in the fins.
We presume that in the absence of joints
these bones break over time and then heal at
different angles, thus giving the fins a misshapen
appearance. Interestingly, this doesn’t seem to
affect the fish adversely. They live to a ripe old age
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
and still eat and swim and breed normally and
don’t show any obvious signs of distress. I still use
these fish and their phenotype to teach Mendelian
genetics to undergraduates and high school
students.
I moved to Syracuse University in July 2010,
motivated to return to the U.S. for a mixture of
professional and personal reasons and continuing
my pattern of transatlantic moves. I was very
fortunate that a postdoctoral researcher in my lab
in the United Kingdom, Dr José Morales, agreed
to move with me, and that a second postdoctoral
researcher, Dr Samantha England, agreed to also
join us several months later, when my United
Kingdom funding for her position finished. Both
Sam and José still work in the lab and they have
been instrumental in the lab’s success here at SU.
I have also been fortunate to work with great
graduate students, technicians, and undergraduates
since I arrived in Syracuse. One of the greatest
rewards of this career for me, although also in some
ways one of its greatest stresses, is managing a
research team. The stress comes from the need to
continuously obtain grant income to maintain other
people’s salaries. The rewards come from working
with and mentoring a talented group of interesting
people and watching them grow and succeed. I
also enjoy the international aspect of this as I have
worked with people from all over the world. At one
point in Cambridge, I was the only British person in
my lab.
At SU, we have continued our research into how
different types of interneurons are made, with the
help of research grants from the National Institute
of Health, National Science Foundation, New York
State, Human Frontiers in Science Program, and
Syracuse University.
Much of our work in the last few years has
concentrated on identifying regulatory genes
that determine which chemical messenger (or
neurotransmitter) specific types of nerve cells use
to communicate with other cells. We have identified
and are continuing to identify regulatory genes
that are important for these processes in different
classes of spinal cord interneurons, both those
involved in locomotor circuitry and those involved
Solvay High School students enjoy observing adult zebrafish
in processing sensory signals such as touch, heat
or pain. In addition, we have started to investigate
in more detail the molecular mechanisms through
which these regulatory genes exert their effects.
In collaboration with two French research groups,
one in Paris and one in Marseille, we have branched
out into studying an unusual sensory nerve cell
found in the spinal cord that contacts the central
canal and cerebral spinal fluid. These cells were
first described almost a hundred years ago, but
until recently no one knew what their function was.
Our collaborators have shown these cells are part
of locomoter circuitry, and they are investigating
their physiological functions in different types of
locomotion while we are studying how the unique
properties of these cells are initially specified.
Recently, we have also started a very different
sort of project, studying the toxicity of two
polyaromatic hydrocarbon compounds that a SUNY
College of Environmental Science and Forestry
chemist, Professor John Hassett, isolated several
years ago from an oily substance that has leached
out of the waste beds around Onondaga Lake into
the Lake. This last project has been conducted
primarily by two undergraduate Honors Program
students, José Marrero’17 and Jason Zheng ‘16
and, excitingly, José has recently been awarded a
prestigious national EPA undergraduate studentship
on the basis of his studies.
Our results from this project are pretty disturbing.
The two chemicals have a very similar structure
to DDT and we have shown that they are much
more toxic to zebrafish embryos than DDT, and
also that exposure to these chemicals early in life
increases the incidence of seizures in a model
of epileptic seizures. These results prompted me
to describe our results to the Onondaga county
legislature at a public hearing about the proposal
to build an amphitheater on top of the waste beds
by Onondaga Lake. We aim to publish our research
this year.
We also hope to expand our toxicology research
this year with a new collaboration with Professor
Shobha Bhatia of the SU College of Engineering.
Professor Bhatia is developing new materials to
help de-contaminate bodies of water like Onondaga
Lake and we are going to help her test whether
these new products are less toxic than existing
materials.
In addition to teaching and research, I’ve always
been interested in communicating the importance
and interest of science to the general public and
increasing general scientific literacy. This started in
my Ph.D. where we were strongly encouraged to talk
to the public and, in particular, groups of volunteers
that worked for the Imperial Cancer Research Fund
(ICRF) in their charity shops. I was encouraged to
talk about the animals I used in my research and
why, so I would usually take small tubes of fruit flies
and zebrafish eggs with me to hand round so that
people could see them.
For many years, there has been a vocal minority
in the UK that is vehemently opposed to animal
research and individuals with these views have
sometimes resorted to violence. The ICRF was
open about the fact that they used animals in their
research, feeling that as a cancer charity it was
easier for them to talk about this and the value of
that research than many other groups. However,
this also meant that there was a section in the
ICRF health and safety manual that discussed in
detail how to check under your car for car bombs.
In addition, the IRA was also very active during my
Ph.D. studies (I was once in the lab listening to the
radio and realized that we were surrounded by three
different bomb alerts – each just a couple of blocks
away)—I used to be glad that I could cycle to work
because I figured my bike was much less likely to
have a bomb attached to it.
Zebrafish is a great animal model for teaching
and also for interacting with children and adults
alike, because zebrafish lay transparent eggs and
you can watch the embryos grow by just looking
down a simple microscope at some eggs in a dish
of water. By the time the eggs are just 1 day old
you can see all the major body organs as well as
a beating heart and individual blood cells flowing
around the embryo.
We also have genetically modified fish in which
specific cells (including nerve cells in some cases)
glow green or red under UV light, enabling one
to see individual cells growing and moving in the
embryos (see Figure 5). In Oregon and Cambridge
I took part in departmental open days where we
showed interested members of the public zebrafish
eggs and adults and the sorts of research that we
do.
While at Cambridge I also took part in a
couple of more unusual schemes. For one, I was
paired with a Member of Parliament (equivalent
to a representative to congress) and I spent
time shadowing him and learning how the UK
governmental processes work and how science
does (and does not) influence government policy.
He also shadowed me and visited my lab to learn
more about our research and how science is
conducted.
I also volunteered for a new initiative to enable
authors and TV writers to contact working scientists
so that they could write more accurately about
science and scientists. While I wasn’t contacted by
any individual writers, I was invited to talk about
my research to a large group of fiction authors in
London.
Since arriving at SU, with the help of many
people in my lab, including many undergraduates
doing research in the lab, I have continued with
scientific outreach. For example, we did a hands
on demonstration and lecture at the Museum of
Science and Technology (MOST) in down-town
Syracuse. Each year we host students from local
high schools to do experiments with zebrafish
similar to those I do with undergraduates in BIO
305, the required lab class for biology majors I
teach each spring, and we have also been involved
for several years in a two-week science summer
school for high school students.
I hope to enlarge on these activities in the future,
while also continuing with the lab’s research and
my teaching and advising of students. Researchwise my main goal for the future is to develop a
transgenic line that labels each different type of
nerve cell in the zebrafish spinal cord, and to use
these to elucidate the genetic pathways that specify
each of these cell types and their unique functional
properties. It’s an ambitious goal but one that I
think is within our reach.
FALL 2016
13
Professor Scott Pitnick, Weeden Professor in the College of Arts and Sciences.
Evolutionary Biologist Professor Scott Pitnick
Awarded Inaugural Weeden Professor in the
College of Arts and Sciences
O
n October 30, 2015, a special award
ceremony took place during which
Scott Pitnick was formally presented
with a medallion acknowledging his
appointment as the inaugural Weeden Professor in
the College of Arts and Sciences. The professorship,
appointed by the dean and awarded to a faculty
member selected from among the entire College of
Arts and Sciences faculty, will support the activities,
research, and teaching of the Weeden Professor.
It was made possible thanks to the generosity of
Morris “Mike” Skiff Weeden ‘41 and his wife, Jane,
both of whom died in 2013.The medallion was
presented by Interim Vice Chancellor and Provost
Elizabeth “Liz” Liddy. Representing the Weeden
family at the ceremony were Morris and Jane’s
daughter, Nicki Weeden, and granddaughter Jamie
Hall.
Scott, who joined the college in 1996, has
been awarded more than $3 million in research
grants since his arrival at Syracuse. Hiss articles
have been featured in some of the most highly
respected scientific journals, including Nature,
Science, Current Biology, Proceedings of the
National Academy of Sciences USA, and Biological
Reviews. Recent contributions by Scott and his
colleagues have revolutionized the understanding
14
of reproductive competition and the maintenance
of species boundaries. Their findings have major
implications for understanding biodiversity and
the fundamental nature of sex differences and
sexual conflict. Scott earned a Ph.D. from Arizona
State University in 1992 and completed a National
Science Foundation postdoctoral fellowship in
1994.
The event, held in the biology department’s
Lundgren Room, was attended by many members
of the Syracuse University community, including
College of Arts and Sciences Dean Karin Ruhlandt;
former deans Sam Gorovitz, Cathryn Newton, and
George Langford; biology department faculty, staff,
and students; as well as several members of the
Biology Advisory Board (BAB). Scott’s wife, Wendy;
daughter Emma; son Wyn; mother, Joan Scherer;
and niece Melanie were also in attendance.
On behalf of the Weeden family, granddaughter
Jamie Hall congratulated Scott, and shared her
comments about what it meant to her to be present
at this ceremony representing the donors—her
grandparents, Mike and Jane Weeden. Ruhlandt
spoke about Scott’s scholarship, his mentorship of
students, and his many contributions to the college
and to the University.
As part of the event, Scott presented some
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
highlights of his current research in a lecture
entitled “The Fundamental Nature of Sex
Differences and the Origins of Biodiversity.”
After Scott’s presentation, a reception and
student poster session were held in the Life
Sciences Complex lobby. A dinner that evening
in his honor was held in the Faculty Club and
attended by members of the biology faculty, Liddy,
Ruhlandt, and members of the Weeden family.
Chancellor Kent Syverud, whose schedule
prevented him from attending the award ceremony,
later hosted a special dinner, along with his wife
Dr. Ruth Chen, during which they expressed their
congratulations to Scott for having been chosen as
the inaugural Weeden Professor in the College of
Arts and Sciences. Scott, who is an avid rare book
collector, was presented with a special gift from the
Chancellor and his wife selected by them based on
their knowledge of Scott’s interests—a rare 1863
first-edition copy of Thomas Huxley’s Evidence as to
Man’s Place in Nature.
Scott later expressed his gratitude to the
Weedens, his appreciation for the award and the
ceremony, and his gratitude to the Chancellor and
his wife.
“Mike and Jane Weeden were extraordinarily
accomplished and generous people. I am honored
Professor Ramesh Raina (Biology Chair), Dean Karin Ruhlandt,
Interim Vice Chancellor and Provost Elizabeth Liddy, Nicki
Weeden, Professor Scott Pitnick, Jamie Hall.
Chancellor Kent Syverud and his wife, Dr. Ruth Chen, present Professor Scott Pitnick
with rare 1863 first edition of Huxley’s Evidence as to Man’s Place in Nature.
Professor Scott Pitnick presents highlights of his
current research.
to hold a position that bears their name,” he said.
“As an academic whose research passions tend
toward the esoteric (e.g., the evolution of mating
systems and the formation of new species), it is
deeply rewarding to get this level of confirmation
that you are part of an institution that genuinely
recognizes and values scholarship in all its forms.
The incredible turnout and unbridled support
of colleagues, students, and members of the
administration, in addition to family and friends,
during the induction ceremony and dinner left me
with fond memories that will last a lifetime.
“I was especially touched to meet with
Chancellor Kent Syverud and his wife, Dr. Ruth
Chen, who generously presented me with a
personal gift of a beautiful 1863, first edition
of Thomas Henry Huxley’s Evidence as to Man’s
Place in Nature! My being a rare book collector
aside, it was evident that they personally valued
my accomplishments and wished to share in this
occasion with me, which was deeply moving.”
A former captain in the U.S. Army, Morris Weeden
received a B.A. in political science from the college
before going on to receive an MBA at Harvard
Business School. A lifetime trustee of Syracuse
University and a member of the College’s Board
of Visitors, he and his wife, Jane, were generous
supporters of Syracuse University. Morris held
executive positions at Bristol Laboratories and
Morton Thiokol before finishing his career as a
business consultant in the health care industry. He
also served as the president of the National Alumni
Association and was once chair of the Corporate
Advisory Council.
Bio@SU thanks Sarah Scalese, associate vice
president for university communications, for use of
some material in this article.
FALL 2016
15
RECENT FACULTY HIRE
CARLOS A. CASTAÑEDA
Assistant Professor, Biology and Chemistry
C
arlos Castañeda joined the departments of biology and chemistry in
August 2014 as the first joint hire appointed in both departments.
His main interests are in the areas of biophysics, biochemistry and
structural biology. He earned a B.A. in chemistry and mathematics
from La Salle University in 2001 and a Ph.D. in biophysics from Johns Hopkins
University in 2008, working in the lab of Bertrand García-Moreno. During
his graduate work he was supported by a Burroughs-Wellcome Predoctoral
Fellowship and as a postdoc he was supported by an NSF Postdoctoral
Fellowship in Biology. His postdoc was in biochemistry and structural biology
working with David Fushman at the University of Maryland, College Park.
His lab is interested in chemical biology and physical biochemistry. Their
main focus is on post-translational modifications of proteins, some of which are
relevant to different neurological disorders. They use methods such as nuclear
magnetic resonance (NMR), mass spectrometry and bio-organic chemical
models in their studies. Carlos has received support for these studies from a
Ralph Powe Junior Faculty Enhancement Award, an ALS Starter Grant Award,
and a Nappi Family Research Award.
While there are less than 20,000 protein-coding genes in human DNA,
1,000,000 proteins are predicted to exist in the human proteome. This
large discrepancy is addressed by the more than 200 post-translational
modifications (PTMs) that modify the structure, dynamics, and function of
proteins inside cells. The lab is focused on elucidating the roles of three posttranslational modifications in proteins. Projects revolve around three questions:
(1) What is the structure of the PTM itself? (2) How is the PTM recognized by
downstream receptor proteins in the cell? (3) What is the effect of the PTM on
biological events in the cell? His group collaborates extensively with others at
SU and Upstate Medical University.
The projects revolve around three different PTMs, specifically ubiquitination,
ufmylation, and citrullination. Ubiquitination is the attachment of ubiquitin or
polyubiquitin (a chain of ubiquitin (Ub) molecules) to target lysine residues
in target proteins, using a hierarchy of enzymes called E1, E2, and E3.
Polyubiquitin chains are defined by the isopeptide bond that links a lysine
residue (K6, K11, K27, K29, K33, K48 or K63) of one Ub to the C-terminus
of another Ub. Each polyubiquitin chain of a different lysine linkage confers
a different biological outcome in the cell. The group’s hypothesis is that
polyubiquitin chains of different lysine linkages adopt different conformations
in solution, and that is the molecular basis for how these chains elicit different
signals in the cell. The group is interested in determining the interactions
between non-canonical polyubiquitin chains and their interacting partners.
Ufmylation is a recently discovered PTM that attaches the Ufm1 protein to
target lysines of substrates. While ufmylation is analogous to ubiquitination,
Ufm1 exhibits only 16 percent sequence identity with Ub; thus Carlos’ lab
believes it likely interacts with a completely different set of proteins than Ub.
Ufmylation has been implicated in breast cancer, blood disorders, and mental
illness disorders, including schizophrenia. The lab is employing chemical
16
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
biology methods to study Ufm1 chains both in vitro and in vivo. The goal is to
characterize the structure and functions of these proteins.
Lastly, citrullination is a small modification that converts positively charged
arginine amino acids in proteins to neutral citrulline residues. This PTM is
mediated by a special class of enzyme (PADs) that is calcium-activated. This
PTM is implicated in multiple sclerosis and other autoimmune disorders, such
as rheumatoid arthritis. Here the lab’s goal is to study the structural, dynamical,
and functional effects of citrullination in target substrate proteins to better
understand the consequences of this PTM.
RECENT FACULTY HIRE
JESSICA MACDONALD
Assistant Professor of Biology
J
essica MacDonald joined the Department of Biology in August 2015.
Her overall research interests center on understanding the cellular and
molecular mechanisms that control neuronal development and the
disruptions in these mechanisms that underlie neurodevelopmental
disorders. Jessica received a B.Sc. degree with honors from the University of
Toronto and a Ph.D. in neuroscience from the University of British Columbia.
She was awarded pre-doctoral fellowships from the Natural Sciences and
Engineering Research Council of Canada and the Canadian Institutes of Health
Research for her doctorate research identifying distinct, sequential stages of
neuronal development that are controlled by different epigenetic regulators. She
continued to investigate molecular mechanisms regulating neuronal development
during her postdoctoral fellowship with Dr. Jeffrey Macklis at Harvard University.
Her work focused on identifying novel molecular controls over development
of the neocortex and disruptions underlying the severe neurodevelopmental
disorder Rett syndrome, caused by mutations in the epigenetic regulator MeCP2.
Jessica’s research identified disrupted cellular pathways downstream of MeCP2,
uncovering a potential new therapeutic target for this devastating disorder. She is
continuing to pursue this research at Syracuse University.
The brain contains thousands of distinct types of specialized cells, both
neurons and glia, which enable it to perform such complex tasks. During
development, these distinct neuronal and glial subtypes must be generated in
the correct number, migrate to the appropriate position within the brain, and wire
together in a precise way. Even subtle disruptions in one of these processes can
drastically alter the way the brain functions, resulting in a neurodevelopmental
disorder. Extensive research into neurodevelopmental disorders, such as
autism and schizophrenia, highlights that genetics alone fail to account for
these complex syndromes, leading to growing evidence that epigenetics and
gene-environment interactions play critical roles in neuronal development and
cognitive function. Jessica’s research employs in vivo and in vitro models and
an array of molecular and cellular biological and microscopy approaches to
investigate how environmental factors and nutrition (e.g., vitamin D, folic acid,
high-fat diet) alter the epigenome and modify neuronal development and
function. The goal of her research is to understand how these extrinsic factors
intersect with fixed genetic susceptibilities to alter the probability or severity of
neurodevelopmental disorders.
Jessica enjoys cooking for friends and family and exploring new cuisine. She
is particularly known for her baking. When she gets a chance to get a little farther
away from the lab, she loves to travel and explore new corners of the world.
FALL 2016
17
UNDERGRADUATE STUDENT PROFILE
Luke Strauskulage ’15
W
hen I entered Syracuse University, I enrolled as a dual
biotechnology and secondary education major. I was
torn between my passion for science and my love of
teaching, so I split my time between these two pursuits.
I began working in a lab as an undergraduate
research assistant. Meanwhile, I also worked in
local schools in the Syracuse area as a pre-service
teacher. While spending time with these students,
I saw many of the difficult problems that teachers
face in urban districts. Because so many of these
problems are the result of systemic disadvantages
within our society, it felt like I could not attack the
core root of these issues as a teacher. I would
often only be able to empathize with my students
instead of actually uncovering solutions to make
their lives better. Meanwhile, I realized that I was
growing more enthusiastic about my research and
my potential in the lab.
I decided to change my education major to a
minor and focus more time on pursuing a career
in research. As I saw it, working in the lab might
allow me to make discoveries that can be utilized to
address and perhaps solve fundamental problems.
However, education is still a critical component
of my future career goals, but I have shifted my
focus from secondary education to teaching at the
university level. A career in academia will provide
me with a rewarding balance between guiding
students in the present and making discoveries for
the future.
I first became involved in research at Syracuse
University when I joined Professor Jon Zubieta’s
lab in the chemistry department. As a freshman,
my role in the lab was primarily learning more
about inorganic chemistry while helping a graduate
student produce a variety of crystals. I was able
to generate several novel crystal structures, and
the data I helped produce has been included in
two publications. Also, the crystal structures that I
helped create could be used as building blocks to
make larger arrays with unique chemical properties.
The most exciting application of this kind of
research would be utilizing these components to
create a structure that could be used to store and
transport other compounds, such as alternative fuel
sources that are better for the environment.
While in the Zubieta lab, I discovered I enjoy
thinking about problems at the molecular level in
order to better understand how components can
come together to create order. I was interested in
applying the perspective I gained to studying living
things at the molecular level, so I began looking
for a research position in a molecular biology lab.
I found that opportunity as a sophomore when
I began working in Professor Ramesh Raina’s
18
lab in the department
of biology. Professor
Raina’s lab focuses on
studying the genetic and
molecular mechanisms
that regulate plantpathogen interactions.
My project in the
Raina lab involved
studying two previously
uncharacterized
genes in the model
plant Arabidopsis
thaliana. These genes
encode small defenseassociated (SDA)
proteins that have
homologs in a variety of crops. All SDA homologs
contain the same novel seven amino acid motif
at their N-terminus, which suggests this sequence
plays a critical role in SDA protein function.
I worked to characterize the role these plant
proteins play in molecular defense against the
bacterial pathogen Pseudomonas syringae. This
gram-negative bacterium affects a wide variety of
crops eaten by humans. Studying conserved genetic
pathways expressed in response to P. syringae
might help uncover ways to genetically modify
crops in order to reduce crop losses. Also, crop
species that are more resistant to pathogens might
reduce the need for pesticides in order to keep
crops healthy. Using fewer pesticides could reduce
the cost of producing crops, making food more
affordable and reducing many negative impacts on
the environment caused by the agriculture industry.
Previous research in the Raina lab had shown
small defense-associated Protein 1 (SDA1) is an
essential protein for defense against bacterial
pathogens in Arabidopsis. For my project, I
characterized Small Defense-Associated Protein 2
(SDA2). If a role in defense is conserved between
these two homologs in Arabidopsis, then it makes
it more likely that SDA homologs found in crop
species are also vital to defense against pathogens
like P. syringae.
In my studies of the role of SDA2 in plant
defense, I employed transgenic lines that produce
interference RNA (RNAi). Theses RNAi lines encode
an antisense transcript of the SDA2 gene that binds
to the native SDA2 mRNA through complementary
base pairing. This creates double-stranded RNA
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
(dsRNA) that is degraded in the cell by nucleases
that recognize such molecules. In turn, this
reduces the amount of SDA2 mRNA available for
translation into SDA2 protein and, therefore, the
overall amount of SDA2 protein synthesized by
the plant. (To prevent off-target effects, the RNAi
constructs were designed to specifically bind to
unique sequences on SDA2 transcripts that are not
homologous to SDA1 mRNA.)
I was then able to perform assays using these
transgenic lines and wild-type (WT) plants to
compare defense against pathogens in Arabidopsis
plants with normal and reduced levels of SDA2. To
monitor immunity, growth assays were preformed
by infecting wild-type plants alongside SDA2 RNAi
knockdown lines with a standardized amount
of P. syringae. Following a consistent incubation
period, plants were observed to assess the degree
of infection, and bacteria were isolated from
plants and quantified to compare bacterial growth
between transgenic lines and WT plants.
When infected with P. syringae, SDA2 RNAi
knockdown lines appeared sicker than WT plants
that maintained normal levels of SDA2 (Figure 1).
There was also more bacterial growth in transgenic
lines with reduced SDA2 than in WT plants. These
results indicate Arabidopsis plants are more
susceptible to bacterial infection when lacking
SDA2, and SDA2 is likely involved in bacterial
defense in Arabidopsis.
To further investigate the role of SDA2 in
bacterial defense, I used reverse transcription
polymerase chain reaction (RT-PCR) to assess the
expression of known defense genes in Arabidopsis.
Plants activate the salicylic acid (SA) hormone-
Figure 1: Disease phenotype from four-week-old plants infiltrated with P. syringae strain Pst D3000 at a
titer of 5x105 colony forming units (cfu)/mL. Photographs were taken three days post infiltration (dpi).
signaling pathway in response to bacterial infection.
This allows them to defend against pathogens like
P. syringae that leech nutrients from host cells. To
monitor activity of this signaling pathway, I analyzed
the transcript levels of downstream defense
marker genes in the SA-signaling pathway called
pathogenesis-related (PR) genes.
If SDA2, like SDA1, functions in the SA-signaling
pathway, then I predicted the transcript levels of PR
genes would be reduced in SDA2 RNAi knockdown
lines. When compared to WT plants, transcript levels
of downstream defense marker genes were lower
in transgenic plants with reduced levels of SDA2
(Figure 2). This suggests that SDA2 is an important
upstream member of this bacterial defensesignaling pathway.
honors thesis on my work with SDA proteins, and
am currently working with the Raina lab to publish
my results from this project in the upcoming
months. For my work on this project, I received
the Goldwater Scholarship and the Astronaut
Scholarship in 2014.
Part of what made my project successful was
spending my summers in Syracuse working in the
lab. This was possible because I was awarded the
Ruth Meyer Scholarship. This unique opportunity
provided me with funding that allowed me to
work in the lab full-time. I was able to conduct
experiments without balancing other responsibilities
I would normally have to work around during the
school year. I am very grateful for receiving this
honor because it allowed me to exceed my own
her conduct her own research project. I taught her
how to manage her experiments and helped her
prepare to present her work at a poster symposium.
It was very rewarding to help get others involved in
undergraduate research at Syracuse University.
Since graduating from Syracuse University in May
2015, I moved to the west coast to pursue a Ph.D.
in molecular biology at the University of California
San Francisco. Although I am far away from snowy
Syracuse, the training I received there has greatly
benefited me during my first year of graduate
school. I know my time in the biology department at
Syracuse has helped prepare me for undertaking a
thesis project at the graduate level.
Figure 2: Image of transcript levels of pathogen-related (PR) genes, SDA1, and SDA2 isolated from WT
plants and three independent SDA2 RNAi knockdown lines, labeled #3, #6, and #9. Transcript levels were
visualized by generating cDNA using RT-PCR and staining with ethidium bromide. RNA was isolated from
four-week-old plants six hours after infection with P. syringae strain Pst DC3000 at a titer of 5x107 cfu/mL.
Ubiquitin C (UBC) is a housekeeping gene used as a loading control.
Transcript level analysis was also used to study a
potential epistatic relationship between SDA2 and
SDA1. RT-PCR revealed SDA2 RNAi knockdown lines
also had reduced transcript levels of SDA1 when
compared to WT plants (Figure 2). This suggests
that SDA2 functions in the SA-signaling pathway by
positively regulating the expression of SDA1.
As a part of my research program, I have learned
to communicate my results by presenting data
at several undergraduate research symposia at
Syracuse University. I completed an undergraduate
expectations and really move my project forward.
In addition to my lab work, I have taken my
interest in education and made it an important part
of my role in research. As an experienced member
of the Raina lab, I was able to help train new
members, and I had the opportunity to work with
the Louis Stokes Alliances for Minority Participation
(LSAMP) Program. LSAMP focuses on including
students from underrepresented groups in STEM
programs. I welcomed a student from Onondaga
Community College into the Raina lab and helped
FALL 2016
19
UNDERGRADUATE STUDENT PROFILE
Natalie Rebeyev ’15
I
t was 5:30 a.m. on a sunny Sunday in August 2011, and I
couldn’t contain my excitement. As we began the four and a
half-hour car journey from my hometown of Queens, New York,
to Syracuse University, my parents asked me once more, “Are you
sure you didn’t forget anything?”
Not only was I the first person from either side of my family to attend college,
but also one of a very few Bukharian women who pursued a college education
outside my local community. Bukharian Jews originate from the Central Asian
part of the former Soviet Union (Uzbekistan and Tajikistan).
We speak a unique dialect—an amalgamation of Tajiki, Persian, and Hebrew
languages—and follow distinct traditions dating back many centuries, while
trying to assimilate Western cultural norms. Typically, young women do not
pursue an undergraduate degree away from home and some get married at a
young age. My mother, who got married at 18, was a nurse in Israel and was
accepted into the nation’s top medical program. Unfortunately, she was unable
to pursue her dream because my parents moved to the United States for
economic reasons a year before I was born.
As a little girl, I wanted to follow in my mother’s footsteps and ‘playing doctor’
intrigued me. Knowing that I had an innate interest in medicine, I started to
volunteer at a nursing home at the age of 11. This was my first exposure to
a health care setting. It instilled in me a deep respect and admiration for
physicians and reverence for the doctor-patient relationship.
My desire to gain clinical exposure and learn about biomedical research
occurred when a schwannoma—an embarrassing, but benign growth of nerve
cells—developed on my tongue. Instead of being upset, I dived into research and
sought a way to reduce the growth without surgery; this sparked a love for learning
about the human body.
Together, these experiences enabled me to witness the care physicians provide
and developed my curiosity for medicine.
In high school, while others were bored to tears with the C-fern plant and the
fruit fly, I found them fascinating. As a student in the Carl Sagan Science/Math
Honors Academy at Forest Hills High School, I competed as a semifinalist in the
New York City Science and Engineering Fair.
Through the Jewish Child Care Association’s Bukharian Teen Lounge (BTL),
an organization that helps immigrant teens successfully integrate into the
larger American community while maintaining their cultural heritage, I did three
internships at Beth Israel Medical Center in Manhattan: one in the operating room,
one in the cardiac surgery ICU, and one in the endoscopy unit.
During the first internship, I shadowed an orthopedic surgeon, but I was able to
observe other cases. One day, I found myself emotionally shaken while observing
surgery on a 10-year-old patient with cerebral palsy. Afterward, I felt frayed. We
were so close in age (I was 16); I wondered why his innocent years were burdened
with disease.
Through this experience, I recognized that medicine has harsh realities fraught
with difficult moments, but these can be balanced by great personal satisfaction
in helping others through clinical treatment and biomedical research.
When I observed oncologic surgery, I wondered how cells in the human
body could undergo such malignant mutations. Through these procedures I
saw the artfulness of surgery and the true beauty of medicine. I observed how
technological and biomedical advances can extend and enhance a patient’s
quality of life.
20
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
This helped clarify my desire to pursue a medical degree. After obtaining SAT
preparation and college application guidance from the BTL, I ranked my top
choices. My heart was set on the Sophie Davis School of Biomedical Education—a
competitive program that accepts 75 students from the Tri-State area to begin
their rigorous medical training as primary care physicians. Although I got in, I did
not know what other opportunities were waiting. During February of my senior
year in high school, I was invited to apply for a Coronat Scholarship at Syracuse
University.
Accepting the invitation to attend Syracuse University on the Coronat
Scholarship was life changing. As a biology major, I marveled at the wonders of
evolution and developed a deep-seated curiosity about human biology, especially
about how things go wrong to cause disease.
This inquisitiveness led me to pursue both biomedical research and clinical
interests while at college. I became involved in a plethora of opportunities that
emphasized transcending classroom study by
obtaining real-world experiences both locally and
globally.
Through the Coronat program I was able to study
comparative health policy in Geneva, Morocco, Spain,
and Amsterdam. A summer later, I was awarded the
Clements Internship Award to do a cancer research
internship in Israel as an ARISE Scholar.
As a campus leader, I was a founding member of
the NY Nu chapter of Phi Delta Epsilon International
Medical Fraternity, and later served on the
national board as the international premedical
student representative. As president of Chabad
House, I engaged with peers from all academic
disciplines and stayed involved with Jewish life on
campus. Through the Remembrance Scholarship, I
represented Theodora Cohen who perished in the
Pan Am Flight 103 tragedy and I helped organize the
service event for Remembrance Week.
As I reflect on my undergraduate memories, a
few stand out as particularly transformative. In April
2012, I attended a seminar by Nobel Laureate Dr.
Aaron Ciechanover of the Technion’s Cancer Research
Center (Israel) at SUNY Upstate Medical University.
Dr. Ciechanover and two of his colleagues won the
Nobel Prize in chemistry in 2004 for their discovery
of ubiquitin-mediated protein degradation, the body’s
intracellular mechanism for discarding proteins.
During that seminar I realized research on
ubiquitination and future interventional approaches
to cancer treatment through drug targeting could
help millions of patients worldwide. That moment
helped crystallize my goals. I envisioned conducting
translational biomedical research in my future career.
This approach would enable me to bridge the
gap between basic scientific advancements made
in the laboratory and new and improved treatments
for patients in the clinic. By engaging in benchto-bedside translational medicine, I will improve
prevention, treatment, and/or diagnosis of a disease
for individuals and populations.
The summer of my sophomore year, I had a
brief cancer research internship at the Technion in
the lab of Dr. Amir Orian. I worked on deciphering
the role of a protein in innate immunity in the
fruit fly. To combat disease, Drosophila relies on
defense mechanisms shared with higher organisms.
The NF-κB family of transcription factors (TFs) is
required for host response against infection, thereby
controlling immune and inflammatory response. The
NF-κB family of TFs regulates antimicrobial peptide
expression activated by two evolutionarily conserved
pathways—toll and immune-deficient (IMD).
My project aimed to characterize the role of
degringolade (Dgrn), a small ubiquitin-like modifier
(SUMO) targeted ubiquitin ligase and the sole
ortholog of mammalian RING finger protein 4,
which connects SUMO and ubiquitin pathways as it
binds to SUMOylated proteins and targets them for
ubiquitination. Dr. Orian’s lab had previously found
Dgrn is required for gene expression downstream
of the NF-κB pathway during early development.
My project focused on how Dgrn regulates the NFκB signaling pathways, and I posed the following
question: Is Dgrn a shared component of both?
Preliminary results suggested that Dgrn is essential
for Toll signaling but negatively regulates the IMD
pathway.
Figure 1. Summary of how IP3R ERAD occurs. When IP3 is bound to the IP3R, a conformational change
will take place that opens the Ca2+ channel and causes the formation of the SPFH1/2 complex, triggering
IP3 receptor ubiquitination in the coupling domain by recruiting the appropriate E2 and E3 enzymes. The
p97-Ufd1-Np14 complex enables the receptor to be extracted from the membrane and delivered to the
proteasome.
After returning from a motivating summer
abroad, I was selected to be a McNair Scholar in
line with my commitment to research and worked
at SUNY Upstate Medical University in Professor
Richard Wojcikiewicz’s lab. My honors capstone
thesis was titled “Defining the Role of Erlin2, an
ER Membrane Protein of the SPFH1/2 Complex
That Mediates Ubiquitination of the Inositol
Trisphosphate Receptor (IP3R1).”
One of the broad aims of the lab is studying
inositol 1,4,5-trisphosphate (IP3) receptor
(IP3R) down regulation. The receptor allows for
calcium (Ca2+) release upon activation and is of
critical importance because of its implications in
neurodegenerative disease. Autosomal dominant
sensory ataxia (ADSA), a spinocerebellar ataxia with
other neurological signs, is caused by degeneration
of the posterior columns of the spinal cord. This
disease is genetic in origin and is progressive.
ADSA is characterized by cerebellar atrophy linked
to complications involving balance, posture, and
voluntary muscle movements.
ADSA is caused by a mutation in RNF170, a
gene encoding an E3 ubiquitin ligase, an enzyme
facilitating recognition and degradation of IP3R
through the ubiquitin proteasome pathway. Studying
RNF170 and other proteins that associate with
the receptor to carry out receptor degradation is
important because it could open new approaches in
treating ADSA.
IP3 is a secondary messenger generated at the
plasma membrane. IP3Rs play a pivotal role in
linking GPCR-mediated IP3 formation to increases
in cytoplasmic free Ca2+ concentration. The IP3R
is down-regulated through endoplasmic reticulum
associated degradation (ERAD).
This is of great importance because it allows cells
to limit increases in cytoplasmic Ca2+. This could
potentially protect against the harmful effects of
over-activation of Ca2+ signaling pathways, such as
ones that may occur during neuropathologies; it may
even inhibit processes that depend on IP3R-induced
Ca2+ mobilization from the ER (e.g., apoptosis).
Other prominent proteins that play a role in
receptor degradation are found in the erlin1/2
(SPFH1/2) complex, which serves as a recognition
factor and to which RNF170 is constitutively bound.
An overview of the system is depicted in figure 1.
In my studies, I examined the basic growth
patterns of κT3-1 mouse pituitary wild type
cells, replete with erlin2 and lacking erlin2, and
cells replete with RNF170 and lacking RNF170.
I investigated the interaction between erlin2 and
RNF170 by trying to determine if Ubc13 is the E2
enzyme that attaches to the receptor, because it
is the only known E2 to make lysine(K)-63 chains,
by which the IP3R1 is ubiquitinated. This was done
through co-immunoprecipitation (IP) and through the
use of cross-linkers.
The question I posed was: Does Ubc13 coimmunoprecipitate with RNF170 by way of the erlin2
protein? Figure 2 indicates that there was no clear
interaction between Ubc13 (E2) and RNF170 (E3).
FALL 2016
21
selecting the sequence of the guide
RNA, one can cut DNA anywhere.
Previously, the Wojcikiewicz lab
used CRISPR to delete RNF170
and validated that RNF170 is
responsible for catalyzing the
addition of all ubiquitin conjugates
to activated IP3R1. This suggests
RNF170 interacts with many
E2s, most likely including Ubc13
and Ubc7, since Ubc13 is the
only known E2 to build K63linked chains, and Ubc7, which
builds K48-linked chains, is
already strongly implicated in
mediating IP3R1 ubiquitination and
degradation.
When knocking-out RNF170,
Figure 2. Ubc13 does not associate with RNF170 when coimmunoprecipitated with anti-erlin2 antibody. Cells were harvested with no K-48- or K-63-linked chains
1% CHAPS lysis buffer. Anti-erlin2 immunoprecipitates from control (lane resulted; this meant that the
2) and RNF170 KO cells (lane 4) were subjected to SDS-PAGE. The 43- receptor was not degraded. In the
kDa band in lanes 2 and 4 is marked as erlin2. The 21.5-kDa band (lane future, I would suggest knocking out
Ubc13 to show K-63 chains are not
2) marked is RNF170, which is expected for lane 2. No interaction was
made when Ubc13 is not present.
seen for the immunoblots probed for Ubc13 for the control cells (lane
2), thereby confirming that there was no interaction between Ubc13 and This would potentially validate
Ubc13 is the E2 that binds to
erlin2.
RNF170 and the only one to make
Figure 3. Is there an interaction between Ubc13 and RNF170 when immunoprecipitating with ubc13?
Controls cells (only) were harvested with 1% CHAPS lysis buffer. Anti-Ubc13 immunoprecipitates from
control cells (lanes 2 and 4) were subjected to SDS-PAGE. DTT preserves ubiquitin loading on E2 in lane 2.
RNF170 does not bind to Ubc13 (lane 5 is pre-IP).
In figure 3, the IP was repeated and κT3-1 cell
lysates were incubated with anti-Ubc13 antibody,
instead of anti-erlin2 antibody. The results were
negative.
Future direction includes using a DNA editing
system known as clustered, regularly interspaced,
short palindromic repeats (CRISPR/Cas9)—a useful
system that only depends on a guide RNA that
matches the target DNA region and a single enzyme
(Cas9) to make double stranded cuts in DNA. By
22
K-63-linked chains, thereby allowing for degradation
of the IP3R.
After working in three labs in college, I learned
rewards in science come slowly; handling uncertainty
is a part of science, and gratification may be delayed,
but is inevitable. I could not be more grateful to all
of the mentors who guided me along the way. The
biology department, my advisors, the honors staff,
and the Center for Fellowship & Scholarship Advising
(CFSA) deserve a huge token of gratitude for helping
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
me achieve accolades. While applying for graduate
study in an M.D./Ph.D. program, I also applied for
nationally competitive awards. After submitting
applications, preparing for interviews with help from
the biology department and CFSA, and anxiously
waiting to hear back, I was selected to receive the
Gates Cambridge Scholarship, another life-changing
award.
I am pursuing a Ph.D. in medical science in
Professor Paul Lehner’s lab at the Cambridge
Institute for Medical Research, University of
Cambridge. Some of my current projects focus on
membrane trafficking. One project will result in a
genome-wide genetic screen using CRISPR, which
aims to identify the genes required for the cystic
fibrosis transmembrane conductance regulator
(CFTR) to reach the cell surface. This could prove to
be a direct therapeutic benefit for patients with cystic
fibrosis.
Cambridge is a wonderful place to pursue a
science degree (or any degree, for that matter!) for
a number of reasons. The network of notable people
has allowed me to build relationships that will
continue to help me during and after my Ph.D. The
world-class research facilities and immense support
from the Gates Cambridge Scholarship, Hughes
Hall (my college), and the Department of Medicine
continue to motivate me to start each day on a new
slate.
Getting involved with extracurricular activities such
as re-learning Russian and planning the Hughes
Hall May Ball have also been a fun way to start my
journey here. The culture at Cambridge is special;
going to college formals, attending student-run plays,
and being so close to the metropolis of travel are
added bonuses.
My experiences at SU helped me refine my goals
and focus on newfound passions. They showed me
committing to a career which integrates clinical
science and biomedical research, thereby allowing
me to be on the forefront of translational medicine,
outreach to humanity, and technology was a perfect
career choice.
As one of the first Bukharian women from my
community to go away to college, I know overcoming
challenges can be difficult, but with determination,
change is possible. My vocation is an expression of
tikkun olam, a value in Judaism that holds everyone
should do his or her share in repairing the world. It
will enable me to further pursue my ideal of giving
back by prioritizing the needs of my patients, while
also conducting research that will impact large
patient populations.
These values, my cultural background, and my
experiences have catalyzed my desire to devote my
future to biomedical research and clinical medicine
and, hopefully, to inspire young women.
UNDERGRADUATE STUDENT PROFILE
Komal Safdar ’15
A
t a first glance, some might see me as another child of
South Asian immigrants working her life away to become a
doctor one day. While there is some truth to this statement,
I came to Syracuse University for a very different reason—to
become a professional tennis player. At the time, Syracuse was
the only college tennis program in the country that recruited a
team of students who had aspirations of turning pro after college.
I had my plan all set in my head: I would graduate as a pre-med
student-athlete, play on the professional circuit for three years or
more, and then go to medical school.
Being able to play Division I tennis and travel
all over the country was certainly a privilege. In
representing Syracuse, I embodied principles of
teamwork, embraced the integrity of my alma mater,
and learned to become a fierce yet respectful
competitor. I was grateful every day and worked
tirelessly to balance school, family, and friends; at
times, I felt I had two full-time jobs: the student
role and the athlete role. It was a challenge to
balance our rigorous schedule of practices, physical
conditioning, matches, and traveling with pre-med
courses but I learned to befriend the art of time
management, which allowed me to take advantage
of even more opportunities on campus.
For example, my sophomore year, I joined Phi
Delta Epsilon—an international medical fraternity—
and participated in several service and medicallyrelated events that allowed me to delve deeper into
my passions for science and service. I also joined
the Student Athlete Advisory Committee (SAAC), the
advocacy network and voice for the large contingent
of student athletes at Syracuse. By my senior year, I
went on to serve as president of SAAC and learned
valuable leadership skills, as I helped initiate
career-development events and volunteer events
such as reading to children, visiting the VA Medical
Center and Upstate Golisano Children’s Hospital,
organizing toy drives for underprivileged kids, and
doing a fundraiser for the Carol M. Baldwin Cancer
Research Fund.
Although I relished the rush of training and
competing, my purpose for playing was only
completed by giving back to the community
through SAAC. Lastly, I had the good fortune to join
Professor Eleanor Maine in the Syracuse University
Department of Biology in a critical research project
involving Notch signaling.
Notch signaling is a widely conserved
mechanism thought to be present in all
metazoans. It is specifically a form of juxtacrine
signaling, a type of communication between two
bordering cells, that controls the number of stem
cells and differentiation of cells during animal
development. The Notch protein itself spans the cell
membrane—its extracellular domain interacts with
a transmembrane ligand located on the adjacent
cell, while the intracellular domain interacts with
intracellular components that eventually control
transcription of target genes. In Caenorhabditis
elegans, a transparent nematode that was used
as a model organism for my study, there are two
Notch-type receptors called GLP-1 and LIN-12,
which are respectively required for germline
proliferation and correct cell lineage. Both
receptors function in multiple tissues.
Biologists often discover a protein’s function by
“inactivating” its respective gene and observing
the changes in phenotype. Inactivation can be
done by deleting the entire gene sequence or a
significant portion of it. A gene can also be partially
inactivated by changing only a small part of the
coding sequence (creating a “point mutation”). For
example, one phenotype that occurs from deleting
the glp-1 gene is that animals grow up to be sterile.
Using this approach, it was discovered that one
of the post-embryonic functions of GLP-1 is to
allow the somatic gonad to signal the germline
to proliferate. In other words, if there is no GLP-1
signaling, the germline does not develop and no
offspring are produced.
LIN-12, the other Notch-type receptor, is also
involved in multiple cell-cell interactions in the
embryo and larvae, and is distinct from GLP-1
because it acts in many different tissues during
larval development. For instance, it functions in
the so-called “AC-VU cell fate decision.” In larval
development, it is essential that an anchor cell
(AC) forms. Normally, two precursor cells, Z1.ppp
and Z4.aaa, interact via LIN-12 signaling. One
cell becomes an AC, and the other cell becomes
a ventral uterine (VU) precursor cell. The AC is
important for signaling to the hypodermal cells to
initiate vulval development, while the fate of the VU
precursor cell is important for proper formation of
the uterus. If the lin-12 gene is inactivated, then the
larva develops two ACs and lacks a VU precursor,
and normal development is.
My project stems from a study done by Maine
and Kimble (1993) in which they discovered
mutations in the sog-1 (suppressor of glp-1) gene
can partially rescue the mutant phenotype caused
by a partial loss of glp-1 function. The glp-1 partial
loss-of-function mutants make very few embryos,
none of which are viable. The sog-1 mutation
partially rescues the glp-1 mutant phenotype by
increasing the brood size and giving rise to viable
embryos. Surprisingly, the sog-1 mutation by itself
has no obvious phenotype.
Based on these findings, the first objective of my
study was to identify the product of the sog-1 gene.
The second objective was to determine whether
the sog-1 mutations reduced or increased SOG-1
protein activity. The final objective was to determine
if sog-1 mutations might also suppress the lin-12
mutant phenotype.
To determine the identity of the SOG-1 protein,
we initiated a collaboration with Don Moerman and
colleagues at the University of British Columbia
to sequence the entire genome of two strains,
each carrying a different sog-1 mutation. The
DNA sequences were compared with the known,
wildtype C. elegans sequence. The data revealed
only one gene on chromosome I (where sog-1 had
been previously mapped) that contained a unique
mutation in each sog-1 mutant strain. This gene
encodes the protein UBR-5, a HECT-type E3 ligase
that is crucial for ubiquitination—a process required
to mark proteins that need to be degraded. To
confirm that UBR-5 was indeed the sog-1 product,
Xia Xu in the Maine Lab amplified and sequenced
the ubr-5 gene from several other mutant sog-1
strains and found a mutation in each one.
Once we had identified the different sog-1
mutations, we compared the ability of sog-1
deletions and point mutations to suppress glp-1
by measuring brood sizes. The number of embryos
produced by sog-1;glp-1(ts) animals reflects the
size of the germline, and therefore, the level of GLP1 signaling. My results are summarized in Figure
1. From the graph, we can see that the deletion
alleles were comparable to the missense mutations
in terms of brood size; however, the deletion alleles
FALL 2016
23
While the details
above are quite
technical, we concluded
that a mutation in
sog-1 is somehow
upregulating or rescuing
Notch signaling. One
possible explanation for
this is that a mutation
in sog-1 decreases the
rate of ubiquitination,
and therefore protein
turnover, of one or more
components in the GLP1 and LIN-12 pathway.
Figure 1. Suppression of glp-1 by sog-1 alleles. The marker strain shows the
The next phase of the
baseline number of embryos and viable progeny. The glp-1 mutant produced
embryos, but none were viable. The sog-1 deletion allele slightly increased both study is to determine
the number of embryos and their viability. The first missense mutation increased the tissue site of sog-1
action, which will help
progeny viability, while the second point mutation significantly increased the
us better understand
number of progeny as well as their viability
the specific mechanism
had significantly fewer viable progeny. Nevertheless,
of sog-1 in relation to Notch signaling. Anniya Gu
both types of mutations in sog-1 (deletion or
has been working on answering this question and
missense) were able to suppress the glp-1 mutant
several others since I graduated. The findings of
phenotype. Therefore, based on the successful
this study are significant because Notch signaling
suppression using the deletion allele, we concluded
is often deregulated in proliferative disorders such
that the glp-1 mutant phenotype is suppressed by
as cancer, and other debilitating neurodegenerative
sog-1 loss of function mutations.
diseases such as Alzheimer’s.
Professor Maine and I were also curious as to
Overall, my time in the lab not only fueled my
whether a mutation in sog-1 could rescue a partial
interest in the basic sciences related to medicine,
loss of function in the gene lin-12. Phenotypically,
but it has also broadened my perspective on
the lin-12 mutant has two ACs, instead of one AC,
mechanisms of disease. I learned the importance
about 70% of the time. If the sog-1 mutant reduced
of research at all levels in the advancement of
the occurrence of two ACs, that result would mean
medicine and this is the reason I am currently
that sog-1 suppresses the loss of lin-12 function.
continuing my pursuit of research—except now in
To carry out the study, we used fluorescence
cardiology clinical research—at The Christ Hospital
microscopy to visualize the anchor cells in a lin-12
in Cincinnati, OH. Here I am conducting multiple
strain carrying sog-1. A Green Fluorescent Protein
studies including a retrospective cohort study of
(GFP)-tagged protein was used to better visualize
patients who have undergone a relatively new
the AC (Figure 2). After analyzing about 100 lin-12
procedure called TAVR (transcatheter aortic valve
control larvae and about 100 sog-1; lin-12 larvae,
replacement) in order to understand the influence
we found that a significant number were indeed
of over 75 parameters on survival. Although
rescued—that is, about 30% (instead of 70%) of
translating basic and clinical science research to
the nematodes had the mutant phenotype (2 ACs).
better patient care can seem daunting, this is how
Therefore, a mutation in sog-1 partially rescues a
we improve the way medicine is practiced, and I
mutation in lin-12.
hope to continue pursuing the field as a medical
student and physician.
In the end, I did not become a professional
tennis player. In fact, my collegiate career was
drastically different than I originally imagined
because I sustained a significant wrist injury just
prior to my freshman year in college. Nevertheless,
I vowed to play tennis at Syracuse to my fullest
even though I endured two different wrist surgeries.
Rehabilitation, frequent cortisone shots, and
rigorous physical therapy paralleled my demanding
schedule of practices, matches, courses, and
research. At times, this became physically and
emotionally draining, but I drew strength from those
Figure 2. Anchor Cell Visualization. The left column
around me, notably my teammates and coaches,
shows the anchor cells tagged with GFP- protein,
and worked to better my game despite the many
while the right column labeled DIC (differential
setbacks.
interference contrast microscopy) shows cell
Although I knew results from hard work are not
morphology. The top row displays 1 AC (wild
always guaranteed, I am happy to say that my
type) while the bottom row displays 2 ACs (lin-12
partner and I became a nationally ranked doubles
mutant). The white arrows indicate AC(s).
24
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
team, and that the SU team achieved its highest
rank in school history by my senior year. In addition,
although I did not turn pro, being a student-athlete
at Syracuse afforded me a toolbox of skills—
including determination, teamwork, resilience, and
precision—that will enrich and reinforce my career
in medicine.
However, as much as I sometimes want to blame
my injury for not becoming a professional tennis
player and jumpstarting my medical career, I know
this is not true; my mindset and heart changed
over the past four years. The more science courses
I took, the more I became interested in how
each field, ranging from physics to biochemistry,
adds to the comprehensive knowledge required
to understand the pathology of diseases. For
example, I remember being fascinated by how
Bernoulli’s equation which we studied in physics
class explained the pressure changes in the heart
of those people who had aortic stenosis, or a
partially blocked aortic valve, and how it can cause
pulmonary hypertension.
These connections that I started making over the
years made me eager to learn more. Therefore, it
was my courses in combination with my in depth
research experience that catalyzed my passion for
medicine beyond what I had ever imagined. By the
end of my junior year, I knew I wanted to start my
medical career as soon as possible.
I am finalizing where I shall attend medical
school, and I look forward to a career in medical
science with enthusiasm and confidence.
Additionally, as much as my achievements in the
lab and on the court took a great deal of personal
effort, I know that multiple supporters helped guide
me to become the person I am today. I am thankful
to my family, friends, and coaches for never giving
up on me as an athlete and supporting me through
all my decisions. I am especially appreciative to
Professor Eleanor Maine for taking me into her lab
and being flexible with my tennis schedule. The
remarkable staff of both the biology and athletic
departments did much to make my years at
Syracuse University successful, and to help me take
advantage of the unparalleled opportunities I was
offered. Wherever I end up, I am confident that my
time at Syracuse has prepared me to succeed.
Reference:
Maine, E.M., and Kimble, J. (1993). Suppressors
of glp-1, a gene required for cell communication
during development in Caenorhabditis elegans,
define a set of interacting genes. Genetics 135,
1011–1022.
STAFF PROFILE
Kelly Condon
E
xperiments don’t happen without reagents and equipment.
Each lab in the Biology Department depends on a variety
of equipment, whether simple and inexpensive, completely
state of the art costing several hundred thousand dollars or
somewhere in between. Quite amazingly, all of the equipment,
growth media and chemicals used in our department are
ordered by one person, Kelly Condon. Kelly has been with the
Biology Department since 2000, prior to which she worked at
SU for five years as a Senior Secretary at the Whitman School of
Management in TRAC, a collaborative program between Whitman
and Newhouse. Before coming to SU, Kelly had worked for about
six years in several different offices of civil services in the federal
building downtown, including the General Services and the Food
and Drug Administrations in a variety of secretarial capacities.
Kelly joined the Biology Department in a new position for her, Office
Coordinator III and quickly excelled. Not surprisingly her first year review
required by the university saw her receive the highest possible ranking in
17 of 20 categories of performance review. Ever since (in fact from the very
beginning), Kelly has been an outstanding and indispensable member of our
department staff – available for faculty and students alike to order materials
needed to carry out our research and teaching in the department. In 2009
she was promoted to Purchasing and Grants Coordinator. That Kelly invariably
carries all of this out with a smile and an always pleasant outlook makes the
department an even better place to work.
Kelly typically likes to start her day well before much of the department and,
indeed, even before the office officially opens. Those of us who have come by
the department in the early morning hours to check on an experiment or send
an e-mail very early are often surprised to find Kelly already at her desk getting
an early start on the day. In many ways she is like the quiet captain of our ship
making sure we are all on course for another day of experiments and teaching.
The Department was especially pleased in April of 2016 to see Kelly being
recognized by Arts and Sciences for her outstanding work through her selection
as A&S staff member of the month, an honor that goes to an individual who
“consistently goes above and beyond the call of duty” in their work.
Kelly grew up in Syracuse, NY and has spent most of her life here. She is the
proud mother of two sons and a devoted grandmother of five grandsons as well.
When she is not doting on her grandchildren, she enjoys gardening and making
art and a piece of her work was chosen for display at the Everson Museum
of Art in 2005 as part of the “On My Own Time” community arts program
sponsored by the Cultural Resources Council (CRC). CRC and Everson judges
selected her work, “Fungus Cascade,” color, for inclusion in the annual exhibit
from among many submissions by artists employed by a variety of different
local businesses.
FALL 2016
25
GRADUATE STUDENT PROFILE
Liz Droge-Young ’15
M
Nalini Puniamoorthy
ultiple times an hour—that’s how often my
red flour beetles mate. Any species that
shows such extreme behavior is inherently
interesting to people like me. I am an evolutionary
biologist and I focus on reproduction and what
makes some individuals better at reproducing
than others. I am fascinated by outlandish mating
behaviors and spend my time in grad school trying
to understand the evolutionary pressures that govern
mating systems.
Liz maintaining stocks of beetles in jars of flour.
To see how I ended up studying mating beetles,
let’s take a few steps back to my home state of
Colorado. Growing up in a state packed with such
natural beauty, it is hard not to be interested in the
mountain or plains-dwelling animals and plants all
around you.
I did my undergraduate work at Colorado State
University (CSU) in Fort Collins, which is tucked up
next to the Rocky Mountains, affording gorgeous
views as students rush around campus. I majored
in biology, focusing on animal behavior, and
completed a second major in theatre. This is the
point in my personal narrative that leads people to
cock their heads to the side or furrow their brows,
but I can assure you there are many skills that
reinforce each other from both fields. Creativity and
attention to detail are as important in designing
evocative costumes as they are in developing
an experiment to answer a burning biological
question. The two foci deepened my undergraduate
experience and gave me multiple paths to pursue
after graduation.
After graduating from CSU, I did work as
a costume designer as well as work for an
environmental consulting business for the oil and
gas industry. I quickly discovered I greatly missed
thinking and talking about evolution. Specifically,
I wanted to spend more time investigating sexual
selection. Since a particularly intriguing lecture
on mating choices during my undergrad course
work, I was hooked on the topic and it provided an
intriguing area to pursue in graduate study. To that
end Scott Pitnick’s lab, part of the newly formed
Center for Reproductive Evolution, has been a
wonderful match for my interests.
During my thesis research, I have focused on the
remarkable mating system of the red flour beetle,
Tribolium castaneum. You may have encountered
my study organism in your pancake mix or breakfast
26
cereal. The beetles are tiny little critters, about
the size of an ant, and as noted above, they mate
more-or-less constantly. In fact, female red flour
beetles mate way more than necessary to get
enough sperm to fertilize their eggs. A single mating
provides females with enough sperm to fertilize
eggs for many months.
red. Aside from pleasantly resembling twinkling
Christmas lights, the sperm tags give us an
unprecedented insight into what happens in the
female reproductive tract after mating (Figure 1).
Given the flour beetle’s mating quirks and our
unique fluorescent tools, we set out to answer
questions about why they mate so much, and
Figure 1: Mass of red and green fluorescently labeled sperm under fluorescent illumination as found in a
female flour beetle’s reproductive tract after mating to males from both tagged lines.
My studies were initiated when, with the
help of Professor John Belote, I genetically
transformed beetles to produce sperm that under
the fluorescent microscope glow either green or
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
what determines reproductive success in such an
extreme system.
I found that female red flour beetles, which
live in dry granaries and do not consume water,
morphology rapidly evolve based on the shape of
each other.
Males that produce sperm that is a better fit
with female sperm storage organs (e.g., is longer)
fertilize more eggs when females mate with multiple
males. Because the specialized organ is not as
important in red flour beetles, this suggests female
behaviors are more important in determining male
fertilization success. Additionally, rapid changes
in other organism’s reproductive morphologies
are predicted to generate reproductive isolation
between groups and eventually the creation of new
species. Because the red flour beetle’s specialized
sperm storage organ isn’t very important for
determining fertilization success, interacting
reproductive morphologies are not expected to
be a driving force of
diversification contrary
to expectations in other
species.
Aside from
researching the
fascinating mating
habits of beetles,
I have had several
major transformative
experiences in graduate
school. Some have
been for the good, like
my development as a
scholar and meeting and
forming friendships with
bright colleagues in the
department. However,
the most impactful
experience nearly
destroyed me.
Although it is seldom
discussed, mental illness
is frequently experienced
in academia, particularly
by graduate students. In
my case, the challenge
is major depressive
disorder. I want to be
clear that academia
did not cause my
depression, but some of
the skills that make me a
successful scholar have
at times been pushed
to the extreme and
became destructive. On
and off for two years my
life became undeniably
Figure 2: Female red flour beetle reproductive tract under fluorescent
dark, necessitating
illumination after mating to males with red- and green-tagged sperm. Major
a leave of absence
reproductive structures are labeled.
and hospitalization to
sperm from the main chamber is used to fertilize
allow me to focus on my illness and ultimately my
eggs and stored sperm is largely irrelevant. While
recovery. Through it all I had incredible support from
this may sound like a minor distinction, in many
my lab family as well as others in the department
species sperm and female reproductive tract
with whom I shared my experiences.
essentially get a drink of water from the moist
ejaculate transferred in every mating. Because
this moisture positively influences the number of
offspring females can produce, they are up for
mating nearly all the time. Conversely, mating so
frequently is costly for males, and results in shorter
lives when constantly in the presence of females
and thus mating opportunities.
I also discovered female promiscuity in red
flour beetles has other interesting consequences
for males, namely for their sperm. Female insects
typically store sperm to be used for fertilizing eggs
in a specialized organ (Figure 2). Flour beetles
are different; because females mate so frequently
there is a constant reservoir of sperm in the main
chamber of their reproductive tracts. This means
I won’t argue for silver linings of depression, nor
would I ever hope to go through an episode again,
but my experience did refocus my priorities. Now
in addition to watching beetles mate, I advocate
for those suffering from mental illness. I make art. I
prioritize mindfulness. It makes for a very different,
but infinitely more sustainable path than where I
began my graduate career.
A refocusing of priorities also led me to zero in
on a career path. Although I have loved learning
about my promiscuous beetles, I have come to
realize I don’t have the intense desire to be the
one doing the discovering. Instead of pursuing a
tenure-track path I am exploring science writing.
A career in science writing would combine sharing
the thrill of scientific discovery with my passion for
writing. Moreover, it would enable me to play a role
in getting the public excited about the science that
researchers live to do.
I’ve recently begun working with the
communications department of the College of
Arts and Sciences at Syracuse University. The
more time I spend reporting on new research
done by the diverse science faculty the more I’m
convinced science communication is the right
path for me. I’ve had the pleasure of learning and
writing about topics as diverse as plant responses
to climate change to the physics of wrapping
miniscule droplets of water (they look like miniature
empanadas!), and I’ve loved every minute of it.
The biology department in general, and the
Pitnick lab in particular, have played an invaluable
role in helping me define not just my research
and career paths, but the way I now approach the
world. As I contemplate completion of my studies,
I am grateful for the supportive and enriching
environment the biology department has provided
in my development as a scholar and individual.
FALL 2016
27
GRADUATE STUDENT PROFILE
David Lemon
M
y desire to carry out research was born not out of any
predisposition to be inquisitive or love of all things nature,
but rather, out of frustration. After four years as a biology
major, I found the prospect of continuing to commit long lists of facts
and formulae to memory tiresome. My interest in science and biology
had spurred my choice of a major, but I found myself performing
better in my other classes.
I had an inkling that I wanted to be a clinician,
and felt biology was the logical place for me to
be. It wasn’t until a semester project in my senior
year at St. Joseph’s University exposed me to the
world of research that my eyes began to open. The
difference between learning facts or concepts for
class, which had become repetitive, and asking
questions or solving problems through research,
which was exciting, became clear.
The next year I found myself at Rutgers University
working in Professor Nir Yakoby’s Drosophila
melanogaster lab on a project for an M.S. degree.
This involved trying to determine how a specific
molecule at the cell surface can interact with so
many signaling pathways and produce multiple
effects on the fly’s development, both when it is
missing and when too much of it is present.
I got my first taste there for the challenge of
tweaking protocols to chase down elusive results
and for planning experiments no one else had
tried before. This was my first foray into full time
research and it was addictive. A good project is
something like tumbling down a rabbit hole; each
new answer leads to more new questions, and
things snowball rapidly. This can be overwhelming,
but I was fortunate to have good mentors in the lab
who helped keep things in focus and in the right
perspective.
After defending my master’s thesis, I moved
to Syracuse and began working on a Ph.D. in the
Syracuse University biology department. Since
my previous research experience was only with
Drosophila melanogaster, I chose three labs to
rotate through, each of which used different model
organisms.
First, I spent time in Professor Anthony Garza’s
microbiology lab, where I worked with Myxococcus
xanthus, a species of myxobacteria (a name
meaning slime bacteria) which forms a biofilm:
a community of bacterial cells held together by a
slime the cells secrete. Next I worked with Professor
Melissa Pepling and had my first exposure to a
mammalian model organism, again working on
development. In Dr. Pepling’s lab we used mice to
investigate estrogen signaling in the developing
ovary. For my last rotation I moved into Professor
28
Kate Lewis’s lab where I
worked on zebrafish—the
vertebrate model she
uses to study spinal cord
development.
After these rotations,
I decided to join Professor Garza’s lab, where I
resumed my studies of M. xanthus. As noted above,
this bacterium grows as a biofilm on agar surfaces
(and other substrates) with the growing colony of
cells spreading across the surface of the agar by
a peculiar type of motility called gliding motility.
In nature, myxobacteria are predators of other
bacteria and move in pursuit of their prey, which
they kill and digest externally with a combination of
antibiotics and digestive enzymes. When nutrients
become scarce, M. xanthus cells within the biofilm
move toward common centers and form aggregates
called fruiting bodies. Inside these fruiting bodies
some of the M. xanthus cells develop thicker cell
coats, change their shape from rods to spheres,
and become spores (myxospores). These spores
germinate and resume growth if nutrients become
available in the future, and repeat the life cycle.
Gliding motility of M. xanthus is thought to
involve a combination of three mechanisms: (1) pili
which extend from the front of the rod-shaped cell,
attach to another cell or to the substrate, and then
retract pulling the cell forward; (2) a focal-adhesion
type motor which exerts force on the substrate
directly beneath the cell to push the cell forward;
(3) and a slime-gun which secretes the slime from
the rear of the cell.
The direction of cellular movement reverses
periodically, which can give rise to oscillating waves
of cells within the biofilm called ripples. All told M.
xanthus has a number of behaviors more complex
than one would expect from a bacterium. It is
another one of these behaviors that I’m currently
studying and trying to explain.
The genesis of my research began in 1942
when an unusual behavior was observed by Roger
Stanier in the distribution Myxococcus fruiting
bodies on agar plates. They seemed to form along
lines of tension in their environment if tension or
compression was present, instead of in a circular
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
arrangement as observed in the typical circular
colonies that form on unstressed substrates (Figure
1A). This previously unseen pattern resulting from
movement in response to the squeezing or pulling
of the environment was dubbed “elasticotaxis.” The
phenomenon
Figure 1: Colonies of M. xanthus on uncompressed
media (A) are circular and grow radially outward in
all directions, while colonies on compressed media
form ellipses (B). The major axis of an elliptical
colony on compressed media is perpendicular to
the direction of compression (arrowheads). Scale
bar = 1 mm.
remained unstudied for decades until 1983 when
Martin Dworkin suggested elasticotaxis might
be involved in predation by helping the cells in
the moving biofilm sense depressions in their
environment formed by prey bacteria.
In 1999, scientists in Dale Kaiser’s lab took
a systematic, quantitative, and careful look at
elasticotaxis. This lab, where Professor Garza did
his postdoctoral work, showed that when agar
gel nutrient media was squeezed up and down,
bacteria growing on it were more likely to move
and grow in ellipses elongated from left to right
(Figure 1B), rather than equally in all directions
(Figure 1A). In addition, myxobacterial colonies
on compressed agar media display abnormal
behavior in flares–protrusions of large numbers of
cells from the main body of the colony–which move
predominantly away from the colony along the long
which could be useful to bacteria living in biofilms,
axis of the elliptical shape,
possibly for predation, aggregate formation, or
instead of moving radially
fruiting body formation, especially if cells also
away from the center as they
alter their substrate or if large numbers of M.
do on uncompressed media.
xanthus cells deform their substrate’s surface.
More than 70 years after
This would fit well with recent theoretical works
this phenomenon was first
concerning polymer alignment, as well as with older
discovered, I set out to try
studies showing cells themselves are capable of
and uncover what exactly
remodeling their environments to induce this kind
was happening during
of a change.
elasticotaxis. At first, I
While a small difference in the way a bacterium
tried to see if elasticotaxis
harmless to humans moves on a gel doesn’t
was involved in biofilm
seem like much, it is interesting to us for several
development in general, by
reasons. It is a biological response to a physical
testing mutants which had
change—something in the gel the cells are grown
been made for another study
on is changed after compression—and this in turn
in the Garza lab and had
alters the behaviors of the cells. This behavior is
been found to be involved
Figure 2: (A) Average aspect ratios were calculated for 8 colonies
not unique to M. xanthus and we have observed it
early in biofilm development. (yellow) at various distances from an inserted tubing (grey), and average
in species evolutionarily distant from M. xanthus
While some of the mutants
aspect ratios were calculated. These ratios decrease with distance from
(Figure 3), which we interpret as evidence this
we tested did seem to be
the inserted tubing (B). Predicted stress values (C) also decrease with
may be a widely conserved behavior. The
somewhat defective for
increasing distance from the inserted tubing. Average aspect ratios for
conservation of this behavior is especially
elasticotaxis, none completely colonies at a given location correlate with the predicted stress values for
interesting because while the response to
failed to demonstrate the
the same location (D).
compression may be conserved across evolutionary
behavior.
relationship between the stress at a given location
lines, the mechanism of motility varies. Bacillus
I was fortunate, however, that at the time I came
on a compressed agar plate and the aspect ratio
mycoides motility is powered by rotary flagella, but
to Syracuse University a new program had been
(Figure 2D).
as shown in Figure 3, nevertheless displays a strong
established by the National Science Foundation
response to compression of the substrate.
(the Integrated Graduate Education and Research
This told us we seemed to be on the right trail
I hope to determine what is altering the way
Traineeship (IGERT)) to encourage interdisciplinary
and a previously suggested mechanism may be
the cells act during elasticotaxis that produces
and collaborative projects, which I was invited to
involved. That theory—in the admittedly small
these different behaviors. It is even possible I
join. SU’s IGERT program brings together students
field of elasticotaxis—is
and faculty from biology, bioengineering, chemistry,
compression of the gel
physics, and chemical engineering departments to
causes the polymers in
try to solve problems in “soft interfaces,” a broad
the gel to align, and the
term which includes biological and synthetic
behavior of the M. xanthus
membranes, bioengineered and nanostructured
cells is changed as a
environments, and cells’ interactions with their
result of this alignment.
environments.
With help from Professor
At a program retreat where students presented
Yan-Yeung Luk’s research
their findings, my work attracted the interest of
group in the SU chemistry
another student, Xingbo Yang from Professor
department, I began
Cristina Marchetti’s group in the SU physics
to investigate what is
department, and we began working together with
Figure 3: Bacillus mycoides, a species evolutionarily distant from M. xanthus,
happening to the gel
another member of the Prof. Marchetti’s group,
forms asymmetrical filamentous colonies on uncompressed media (A), but
that might elicit such
Pragya Srivastava, to characterize the M. xanthus
more markedly elongated colonies on compressed media (B). These elongated
a response from the
elasticotaxis response as quantitatively as possible.
colonies appear to follow the predicted distribution of stress in compressed
bacteria growing on it.
This was my first exposure to interdisciplinary
media (C).
By looking at the
research; so far it has been a fruitful one. We
way different samples
applied techniques from our respective areas, and
could manipulate this mechanism to induce other
affect the polarization of light, a property called
the project started making more progress.
behaviors such as rippling, to investigate how
birefringence, we discovered there is indeed a
We found there was a relationship between
groups of cells change direction, how fruiting bodies
change in the molecular order of the gel after
the amount of stress in the gel and the degree
attract cells over relatively large distances, and
compression. Agar gel samples before compression
of bacterial response, which we inferred from the
other collective behaviors.
do
not
alter
the
polarization
of
light
because
they
colony’s aspect ratio; the ratio describing how much
The kind of sensing environmental changes that
are a random network. However, immediately
longer a colony’s width is than its height. More
I am trying to understand in M. xanthus has also
after we compress the same gel it becomes
elliptical, elongated colonies have larger aspect
been implicated in a variety of human conditions,
birefringent, meaning the compressed gel does
ratios, while circular colonies growing on unstressed
including cancer cell invasion of tissue, bone repair,
alter
the
polarization
of
light.
This
newly
acquired
plates have aspect ratios close to one.
development, and wound healing, so a greater
birefringence signals a change in the molecular
By pairing data from experiments in which I
understanding of the underlying processes may
orientation: the polymer network that was initially
examined the shape of the colonies to calculate
eventually prove useful in understanding behavior of
random and chaotic is now more ordered as a
their aspect ratio (Figure 2A & B) with our
cells other than bacteria.
result
of
compression.
collaborators’ numerical simulations of the stress
We interpret this to mean bacterial cells on
within the media under the same conditions
compressed gels are detecting and responding to
(Figure 2C), we found that stress was a factor in
a more aligned polymer network. This is something
triggering elasticotaxis. The data showed there is a
FALL 2016
29
ALUMNUS PROFILE
FROM BIOLOGY TO THE
SYMPHONY: HENRY FOGEL
A
fter a 50-year career in
music administration,
I find that people are
often amused when they get
my answer to the question
“How did you get started?”
The truth is that I came
to Syracuse University in
1960 with the intent of
being a pre-med major, and
my biology professor was
a lovely man named Roger
Milkman. The first time I had
to dissect a frog, I literally
fainted. Professor Milkman
was a serious music lover, and
when I discovered this point
of commonality between us,
I started talking about music
with him regularly.
In retrospect, I am moved by the attention he gave an 18-year-old freshman
on the subject of classical music. He finally said to me “You belong in music,
not medicine. That is where you should spend your life.” I kind of remember him
promising to pass me in the first semester biology course if I would agree not to
take the second, though the haze of a half-century may be blurring reality. But
there is no question that it was his urging, and the clear emotion and sincerity
behind it, that made me re-think a career in music.
My problem with thinking of it at the outset of my college career was
simple. I knew I was not a good enough pianist or oboist to have a career as a
performer, I did not particularly want to spend my life as a teacher, and I had
no knowledge that there was a field called music administration. Of course,
Prof. Milkman didn’t know that either—I specifically remember him saying
that he did not really know what positions existed in music that would suit
my talents, but that it was clear to him that I had to work in music because it
meant so much to me. He was absolutely right.
Throughout my high school years, I went as frequently as possible to the
Metropolitan Opera as a standee, to the New York Philharmonic at Carnegie
Hall, and to whatever else I could attend. I regularly went to the Donnell Library
in Manhattan, which had an extensive record collection, some of which you
could take home, and some of which you could only listen to on phonographs
in the library. Almost all of my Saturdays were spent there. I owe my fifty-plus
year career to Prof. Milkman.
A friend of mine (Steve Jacobs) started a full-time classical music radio
station in Syracuse in 1963 (WONO), and ran it for 15 years. It actually began
30
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
in our off-campus apartments on South Crouse Avenue, slowly growing to a
better apartment on E. Genesee Street (a three-bedroom apartment where my
partner had one bedroom, I had a second, the studio was the third, and the
dining room was the office).
Ultimately the station succeeded as a business, but it would be too
generous to say that it thrived. It eked out a living, but in 1977 public radio
came to Syracuse through WCNY, and my partners and I decided to sell the
station to an owner who would change WONO into a pop station, but to donate
the record library to WCNY, which did, in fact, take over the classical music
format, which it maintains to this day.
During the period in which I ran WONO, I became deeply involved with
the Syracuse Symphony Orchestra (the demise of which has saddened me
greatly). I was a member of its Board of Directors from 1967 to1978, and
WONO broadcast their concerts. I also developed a strong connection to their
music directors and to their management, and from that gained a great deal
of knowledge about the field of orchestra administration. I was so close to the
founding music director, Karl Kritz, that I served as a pallbearer for his funeral,
and our son is named Karl in his honor.
In 1968, I suggested to the board and management of the orchestra
that we steal an idea from Jerry Lewis, whose Muscular Dystrophy Telethon
was the only broadcast fundraiser that existed at that time. And so we did a
“radio marathon” in June of 1968 for the Syracuse Symphony, the first such
fundraising broadcast ever on radio, and the first of any kind aside from Jerry
Lewis’s highly successful one.
Henry at the controls at station WONO.
Henry editing tape for station WONO.
The idea caught on and the classical radio program directors of others
stations would call me and ask me if I would help them do similar ones for
their orchestras. And so in 1970 I co-hosted the first Cleveland Orchestra
radio marathon (which was the first orchestra to do it after Syracuse), on
Cleveland’s WCLV, and in 1971 joined the Boston Symphony effort on WCRB.
These radio marathons have morphed into public radio fundraisers for the
stations themselves, but between 1968 and the middle 1990s they raised a
great deal of money for American orchestras, and I myself participated in more
than 100 of them in 26 different cities.
In 1977 I was asked by a volunteer working for the New York Philharmonic
if I would be willing to help them do the New York Philharmonic’s first radio
marathon, scheduled for March of 1978. She had heard about me from a
cousin of hers who was a volunteer for the Houston Symphony, where I had
acted as the main host for a couple of them. Of course I agreed, and helped
them in their advance preparation and then was a main host on the air on
WQXR, New York’s classical station. That effort raised $287,000 (a huge jump
from the $7,800 of the first Syracuse Symphony effort ten years earlier)!
While there, overseeing the production and broadcast, I got to know Nick
Webster, the managing director of the New York Philharmonic. A few weeks
later I was in New York and I asked to see him. I told him I was interested in
the field of orchestra management, but didn’t know how to enter it. He said, “I
am about to have an opening in the orchestra manager position—which is the
person in charge of all operations. Are you interested?” I could hardly believe
it.
And so I became the orchestra manager of the New York Philharmonic in
1978, and then executive director of the National Symphony of Washington,
D.C. in 1981, and president of the Chicago Symphony in 1985, a position I
held for 18 years.
In 2003 I decided that I did not have another union negotiation in me, and
I stepped down from the Chicago Symphony and became president and CEO
of the League of American Orchestras, a service organization representing and
serving all American orchestras. And in 2009 I became dean of the Chicago
College of Performing Arts at Roosevelt University – a position I am still
holding. I also produce a radio program called “Collectors’ Corner,” featuring
unusual recordings, for WFMT in Chicago, which is syndicated internationally
and is heard on WCNY on Saturday evenings at 10 p.m.
In that career I have had the opportunity to work with some of the
greatest musicians of the second half of the twentieth century. One of my first
assignments at the New York Philharmonic was overseeing the logistics of a
tour of Japan and South Korea conducted by Erich Leinsdorf, and one year
Henry searching the record library at WONO.
later another similar tour, but this time with Leonard Bernstein. We established
a friendship that stayed until his death, and that led to the only appearance
he made with the Chicago Symphony (except for one appearance in his youth,
before he was famous).
In Washington, the music director I worked with was the great Russian
cellist and conductor Mstislav Rostropovich. Having him share stories with
me of what his life was like in the Soviet Union was quite an extraordinary
experience. His cherishing of the freedoms that we take for granted gave me
a different perspective on our own country, and helped me put its flaws in
context.
And then in Chicago I got to work with two truly great conductors, Georg
Solti and Daniel Barenboim. Solti was music director of the Chicago Symphony
for my first seven seasons as president, and Barenboim for the final eleven. In
addition to being great artists, these were fascinating human beings.
Solti shared stories of fleeing Hungary in the 1930s because his parents
saw what was coming from the Nazis and got him out to Switzerland. When
we brought the Chicago Symphony to Hungary in Solti’s final year as music
director (1991), he gave a talk on Hungarian television, warning about a newly
rising anti-Semitism in that country, and reminding the country of what he
had fled more than half a century earlier. And with Daniel Barenboim, I had
the privilege of being a small part of the formation of his West Eastern Divan
Orchestra—an orchestra of young Palestinian, Arabian, and Israeli musicians
working and making music together in defiance of the hostilities of their
region.
I also, of course, had the privilege of working with all kinds of great
musicians: Yo-Yo Ma, Itzak Perlman, Isaac Stern, Placido Domingo, Leontyne
Price, Pinchas Zukerman, even Vladimir Horowitz. While some of them were, as
you might expect, easier than others to deal with, all provided amazing musical
experiences that remain in my memory decades after experiencing them.
And now, as the dean of the Chicago College of Performing Arts, at the age
of 73, I find myself surrounded by the next generation of musicians, and am
fueled by the enthusiasm that one finds in the young.
It is quite lovely to observe that a half-century-plus career in music
administration was the result of the supportive advocacy and guidance that a
biology professor gave me back at Syracuse University in 1960. But there is
no questioning the weight that advice had in my life. Prof. Milkman’s caring
support, and the emotion with which he told me that in life one must pursue
one’s passion, turned out to have a huge impact on this pre-med student.
FALL 2016
31
ALUMNUS PROFILE
Garth D. Ehrlich G’87
W
hen I arrived at Syracuse University
on October 20, 1981, it was
decidedly not by design. I was there
because in a rare moment of verbal fluency
I had talked my way into a job at BristolMyers’s new genetic engineering group where
John Vournakis was serving as a consultant.
In what was arguably the boldest move of
my career, I had seen advertisements by
Bristol-Myers (B-M) in Science for senior
scientists while I was working as a technician
at Bethesda Research Labs (BRL). Figuring
that if they were hiring Ph.D.’s they would also
need support staff, I sent in my resume—
and low and behold I was contacted by Dr.
Vournakis who invited me up (expenses
paid!) to interview and give a “chalk talk.”
32
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
John made it all sound so casual, but I was
petrified. I had never given a scientific talk except
as an undergraduate in senior seminar many years
before. However, I was also highly motivated; my
job at BRL had evolved into one of bacterial strain
construction in Escherichia coli, and the late,
great, microbial geneticist Malcolm Casadaban has
recently constructed a novel highly sophisticated
gene fusion vector, Mud(Ap, lac), for studying gene
expression in vivo. I had been planning to use the
Casadaban construction in my work, and so I built
my presentation around it—which my wife at the
time got to hear at least a dozen times.
John loved my presentation and told me on the
spot he was going to have B-M hire me. Over the
ensuing weeks I had a couple of correspondences
with John and finally I pushed him on the issue of
“Did I have a job,” to that he replied “For sure.”
Being naïve in regard to how large corporations
worked, I then marched into BRL and handed
in my resignation post-dated for a month later.
When I next contacted John with regard to my start
date, he allowed as how I didn’t actually have the
job yet. This of course resulted in a great deal of
consternation on my part that I shared with him,
since I was by this time responsible for a wife and
child. To John’s credit and my everlasting relief,
he called me back within 48 hours and said the
paperwork from Bristol-Myers was on the way—I can
only imagine what he had to do.
So now I was on the ground in Syracuse where
I was stationed in John’s lab at SU, because B-M’s
new building to house molecular biology was still
under construction. When I asked John what I was
to work on, he said something to the effect of “go
over to the pill factory and figure out how to make
some industrial biological process better through
genetic engineering.”
All of this brings me to my “back story” which
is, why was I working in industry when I didn’t have
a Ph.D.? I had graduated from Alfred University
in 1977 with multiple honors in biology, and
enrolled that autumn in the virology program at
the University of Chicago. I had chosen UC over
my other acceptances because they had just
constructed the Marjorie B Kovler Viral Oncology
Laboratories.
Even before arriving at UC, I had developed an
interest in retroviruses, which had been shown to
cause cancer in animals, and I was interested in
searching for human retroviruses (this was years
before the AIDS epidemic). I incorrectly assumed
the faculty and students of a laboratory dedicated
to viral oncology would be receptive to a grad
student with my interests. I was wrong and found
both old and young faculty frankly hostile to my
proposals.
I was confused and angry at my reception and
the herd mentality and close-minded attitude
I found, although I had one experience that
illuminated why some scientists stand above the
herd. One evening I was attending a wine and
cheese party for faculty and new graduate students,
mostly feeling sorry for my situation. Late in the
evening as I was considering heading home, an
elderly white-haired gentleman doddered up to me.
Well, as they say, don’t judge a book by its cover. No
sooner did he approach me, when he put his hand
in his pants pocket and took out a handful of corn
(maize) kernels—and my blood ran cold. I tried to
speak, but I couldn’t—remember I was a small town
kid who grew up on a dairy farm—and here I was
face to face with one the most famous scientists of
our age, George Beadle.
He didn’t have to introduce himself after he
pulled out the seeds, because I knew Professor
Beadle was working on the evolution of maize. I
also knew he was taking a lot of heat—even though
he was a Nobel laureate—for his theory that maize
had evolved from a Mesoamerican grain called
teosinte (DNA testing decades later proved he was
right—again).
I patiently listened as he discussed his theories,
then he abruptly stopped and asked me what I was
interested in. With fear clawing at the back of my
throat, I explained that I wanted to look for human
retroviruses as almost all other vertebrate species
studied had been found to have retroviruses. He
paused, and then said “That’s a great idea young
man, I wish you all the luck in the world.” Right
then and there I learned a powerful lesson—most
scientists are just pretenders, the truly great are
different. They either have no fear, or they have
learned to overcome it.
In the years immediately following that encounter
with Professor Beadle, his blessing seemed almost
irrelevant. I dropped out of UC and then spent
years running a dairy, tending bar, driving a truck,
and finally working as a tech in the infant biotech
industry. However, all that was prelude, and as I
look back nearly 40 years later I realize I have been
very fortunate and even lucky.
Multiple career-making opportunities have come
my way, usually in unpredictable and unexpected
ways. My fortunes began to change with John
Vournakis believing in me and, oddly, because
B-M didn’t have lab space for me (which put me
physically in John’s lab). Then John introduced me
to Janet Moore, a young scientist recently recruited
from the NIH who had an adjunct appointment
at Upstate Medical School (now SUNY Upstate
Medical University).
Janet and John had met at some social event,
and she had inquired whether he had anyone in his
lab that knew how to do plasmid preps. Based on
my background, John correctly assumed I had the
knowhow and he volunteered me to teach her. I had
everything ready to go when Janet showed up a few
days later, and as I was picking up a flask I asked
her what she was working on. Janet said she was
collaborating with another young recruit from NIH,
Bernie Poiesz, who had “just discovered the first
human retrovirus.”
The flask crashed to the floor in a thousand
pieces amidst my demand to have her repeat
herself, so I could make sure I hadn’t been hearing
things. Janet was so alarmed at the sudden
decomposition of the glassware it took some time
for me to get her to repeat what she had just told
me. At this point she thought I was quite mad, but
then I explained to her my history with this topic.
A few weeks later I went to a seminar also
attended by Bernie and I marched up to him
after the talk and enthusiastically volunteered my
services. Bernie was also just getting his lab at
Upstate going and was happy to have someone
with molecular biology experience. He told me
he had learned virology and cell culture, but not
molecular biology, while a fellow at the Laboratory
for Tumor Cell Biology.
Thus, began an eight-year studentship with
Bernie that brought his lab and John’s lab together.
At first, since my day job was with B-M, I worked
nights—often from 8 PM to 2 AM—in Bernie’s lab, so
that I had the early evening hours with my family.
Those were fantastically exciting times in the
world of human retrovirology in Syracuse, because
not only had Bernie discovered HTLV-I, a retrovirus
which causes adult T-cell leukemia, but he also had
the first evidence the acquired immunodeficiency
that was emerging among the gay community—later
to be called AIDS—was also likely caused by a
retrovirus.
Bernie had published a paper in the Proceedings
of the National Academy of Sciences (PNAS) as
a med student showing that retroviral reverse
transcriptases (RT) were metalloenzymes, and in
1982 he demonstrated RT activity in the blood of
AIDS patients. This implied a retrovirus might be
associated with AIDS, but Bernie was unable to
culture the presumptive virus. Others using cell
lines created by Bernie while he was at the NIH did
succeed.
From the early winter of 1982 through April of
1984, the last year of which was spent in our new
facility at B-M, I continued the pattern of industrial
scientist by day and retrovirologist by night—all
with John’s blessing. Working for Bristol was by no
means bad; moreover, as with any job, the most
important thing is your boss, and my boss, John,
gave me unprecedented freedom and backed my
choices all the way.
After my extended tour of the pill factory, I
settled on the idea of cloning the amidohydrolase
gene from the fungus Fusarium oxysporum into
the bacterium Escherichia coli. This enzyme is
used industrially to cleave natural penicillin V into
6-aminopenicillanic acid (6-APA) and its side chain.
The 6-APA is the substrate for the production of
semi-synthetic penicillins with broader antibacterial
activity. When I arrived, the process was conducted
by flowing the pen V over beds of disrupted fungal
mycelia. I reasoned if I could isolate and clone
the amidohydrolase gene, I might produce large
amounts of pure enzyme recombinantly and use it
to gain better process control.
Thus, from the outset of my employment I was
the only junior scientist in the entire Industrial
Division to have my own project—let alone one
FALL 2016
33
that I had developed myself.
John and I had, however,
followed protocol and run
it up through the ranks and
it was duly authorized. As
part of this process, I had to
learn enzymology, including
purification, determination of
molecular weights and specific
activities, and also develop a
protocol for extracting RNA from
the fungus and using the RNA in
cDNA cloning.
By this time John had joined
the company as director but still
Garth Ehrlich (left) and Bernie Poiesz (right) as helmsmen on a sailboat
had his professorship at SU.
in Oyster Bay, NY while attending the retrovirus meetings at Cold Spring
However, the industrial politics
Harbor Laboratory in 1985.
were wearing him down and he
left in 1983 to return to SU full
ensconced in Bernie’s lab, I was still an SU
time. His replacement as director
graduate student, and our new chair, Judy Foster,
was someone I’d helped him hire so I was not
graciously agreed to step in as my official mentor
expecting any difficulty, but as I’ve learned through
with John staying on my committee as an outside
life, power does funny things to some persons and
member.
it was not long before we were at odds—chiefly
Having faculty from three schools on my
because he wanted my project.
committee
was another turn of good luck, because
As things were worsening at the pill factory, the
it
brought
me
into contact with a much larger
research I was doing with Bernie and John was
scientific world. Realizing the importance of this
heating up as the AIDS epidemic was exploding. In
accident in my career development, I have always
April of 1984, Bernie was awarded a major grant
made it mandatory that my Ph.D. students have an
from the NIH, and he kept a promise made a year
outside-the-university committee member.
earlier to hire me at the salary of a postdoc if he
1985 turned out to be a momentous year in
succeeded in obtaining funding. This was partly
our
lab. The Polymerase Chain Reaction (PCR)
because I had years of laboratory experience at
was
being developed as a diagnostic at Cetus in
this point, my need to support a growing family (my
Emeryville, CA, and the gods of luck conspired to
second son Nathan was born that month), and the
turn things my way again.
fact that I’d worked for him for two years without pay.
While an employee of B-M, I had met Brian Issell
It was also agreed I would work on my Ph.D.
and
his colleagues, who were medical oncologists
dissertation at SU with both John and Bernie
on staff there. They were also colleagues of Bernie’s
serving as my mentors. Since I had been taking
because they served on his clinical service at
course work while working at B-M, by the time
Upstate six weeks a year to maintain their clinical
I started as a full-time student in John’s lab I’d
skills. However, they left B-M en masse when their
completed sufficient course work that I could focus
clinical privileges were summarily revoked and
solely on research.
subsequently joined Cetus.
This arrangement held for over a year and I
Being the only physicians on staff at Cetus,
loved working in John’s lab as he had a terrific
they
were asked by the new director of infectious
group of graduate students including Mike Lane, Liz
Lombardi, Bill Curtis, Barb Sneath, Bob Rehfuss and diseases research, John Sninsky, to suggest
someone he might collaborate with to determine if
Keith Wells. This intellectual mix was stimulating
PCR could be useful as a diagnostic for HIV. They
and we also had a fair amount of interaction from
put John in touch with Bernie, and I will never forget
the graduate students in Dave Sullivan’s lab. We
the day that Bernie came back from California and
also had a postdoc in the lab, Calvin Vary, who
announced to the lab that Cetus had developed
provided a lot of technical expertise and challenged
an in vitro DNA amplification method. No one
us intellectually. For the most part we were a pretty
else seemed particularly interested, but I was
friendly and tightly knit group and I learned about
thunderstruck as I was familiar with in vivo plasmid
mentorship from watching John. He did not treat
amplification methods, but couldn’t conceive of an
everyone the same and that was because not
in vitro method.
everyone had the same set of talents, rather he
After the lab meeting, I pursued Bernie
adjusted his style to fit the needs of the individual
relentlessly to tell me how it worked, but being one
students.
of the most, if not the most, ethical person I’ve
Then the news came John was leaving to go to
ever known, Bernie wouldn’t tell. He had signed a
Dartmouth and our world was about to change
nondisclosure agreement since the patents were
drastically. What saved me was the fact I had a
only then being written. Stumped and miffed I went
spare mentor. Although by this time I was actually
34
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
back to my desk and started drawing pictures of
DNA and oligomers and pretty soon I had figured
out what they must have been doing—as the genius
was not in the technique, it was in breaking the
paradigm that you could amplify DNA.
Cornering Bernie a bit later I told him what I’d
figured out and explained what they must be doing.
Bernie appeared flustered and he said, “But I didn’t
tell you how they were doing it” — and I said, “Don’t
worry you didn’t and I won’t tell anyone until you
tell me its okay.” However, I did make him promise
to send me out to Cetus at the first opportunity,
and shortly thereafter I began a long and fruitful
collaboration with John Sninsky, Shirley Kwok, and
David Mack among others that lasted throughout
the remainder of my Ph.D., post-doctoral studies,
and my early years as a principal investigator (PI).
That fall of 1985 also brought the bitterest pill
of my life; my father’s brain cancer, which I had
diagnosed the previous year, took his life. One
of the “perks” of being immersed in an oncology
division is that you learn signs and symptoms. We
had always been close and his illness and death
almost derailed my Ph.D. several times.
What kept me going was my father himself
had given up getting his Ph.D. because of family
responsibilities, and he did not want the same
thing to happen to me. So, although he didn’t live
long enough to see me get my degree, I promised
him I would and I think he believed me. Bernie did
everything in his power to help my dad, but even
thirty years later we still can’t alter the progression
of grade 3 and 4 gliomas.
The next few years were just a blur, being at the
nexus of human retrovirology (HIV/AIDS) and PCR I
was so busy everything else just seemed to vanish
into the background. The power and versatility of
PCR was turning out to be even more spectacular
than I, or anyone, first imagined. Suddenly, so many
Garth and sons Ian (left) and Nathan (right) on the
occasion of Garth’s graduation from SU.
things we used to do in the lab that were difficult
were now routine both in terms of diagnostics and
cloning.
This was truly a revolutionary technology. We
published papers demonstrating HTLV-I, in addition
to causing Adult T-Cell Leukemia and a spectrum
of other lymphoproliferative diseases, could also
trigger a deadly a demyelinating disease—tropical
spastic paraparesis—that was very similar to
multiple sclerosis.
In addition, we discovered HTLV-1 infection
altered DNA methylation patterns on a genomewide level. We also found many patients in high-risk
populations were infected with two or even three
retroviruses, resulting in very complex clinical
scenarios. Our studies also revealed antibodybased diagnostic screens for retroviruses were
insufficient to adequately protect the donor blood
supply.
In 1989, I decided to move on from Bernie’s lab
because there was no hope of a permanent faculty
position at Upstate due to New York State budget
realities. I quickly landed a plumb tenure-track job in
the pathology dept at the University of Pittsburgh (UP).
This happy result was based on my work developing
and utilizing PCR technology and our extraordinary
productivity. I had more than 20 papers at this point
including publications in the Proceedings of the
National Academy of Sciences (PNAS) and the New
England Journal of Medicine (NEJM).
At Pitt I spent the early to mid-nineties
developing molecular diagnostics (MDx) both for
patient care in the UP Medical Center (UPMC)
hospitals, and as a novel academic discipline. I
oversaw the development and operationalization
of one of the first CAP (College of American
Pathologists) and CLIA (Clinical Laboratory
Improvement Act) certified MDx labs to support the
giant UPMC liver transplant program.
Along with my chair, division director, (Drs.
Michalopolous and Cooper) and a number of likeminded forward-thinking diagnostic providers, we
formed the Association for Molecular Pathology
(AMP) for which I served as the one of the first
co-chairs of the infectious disease section in
1995. I also authored the first textbook in MDx
for infectious agents. PCR-based diagnostics in
Infectious Disease, which was published in 1993
by Blackwell.
At the same time I was establishing my research
lab where I was continuing to do retroviral studies
focusing on the human T-immune response, and
the generation of genomic diversity by HIV following
infection, as well as the evolutionary constraints
on the limitations of that diversity. As a member
of the Multi-center AIDS Cohort Study (MACS), I
had a joint appointment in the infectious disease
and microbiology dept of the Graduate School
of Health. I was, however, also at the center of a
nexus because I had contact with multiple brilliant
clinicians in many departments and hospitals who
were interested in the application of MDx to their
individual disciplines.
One of these investigators stood out as an
individual of tremendous intellect and insight: Chris
Post, a pediatric ear, nose, and throat surgeon/Green
Beret with whom a forged a near quarter-century
partnership that led to numerous paradigm shifts
in our understanding of chronic bacterial infections.
Together, we would go on to publish more than 75
papers together, including eight in the Journal of the
American Medical Association (JAMA).
Our collaboration began with a seemingly simple
question posed by Chris: why is it possible to
culture bacteria from acute middle-ear infections,
but nearly impossible from chronic middle ear
effusions?
Our first task was to determine if the chronic
inflammations were actually the result of bacterial
infections, since they were culturally sterile and
did not respond to antibiotic treatment. Using
PCR- and RT-PCR-based assays, and human and
experimental animal middle-ear specimens, we
showed that these sterile antibiotic-recalcitrant
effusions contained bacterial DNA and the DNA
was inside metabolically-active bacteria.
These paradoxical results combined with
my reading of the microbial ecology literature
by Bill Costerton led me to propose that these
chronic infections resisted antibiotics and were
unculturable because the bacteria had gone
through a metamorphosis from single rapidly
dividing planktonic organisms to a more quiescent
multicellular structure called a biofilm. This became
known as the biofilm paradigm of chronic bacterial
infections, and although we initially proposed it
to explain the clinical conundrums associated
with childhood middle-ear disease, it quickly
become apparent to us (although not the rest of
the clinical world) this was a profound concept
with applications across essentially all clinical
specialties.
Out of this work began another enjoyable
collaboration because Bill Costerton was
delighted to have someone in the medical world
pick up on his ideas. In our initial collaboration,
we used confocal and electron microscopy to
show definitively that the common pathogen
Haemophilus influenzae could form robust biofilms
on the middle-ear mucosa of our chinchilla animal
model.
Subsequently, with Joe Kerschner providing
pediatric middle-ear biopsy specimens, we showed
both chronic otitis media (OM) and recurrent acute
OM were biofilm diseases, and even though the
cultures were negative and the children had been
treated with multiple courses of antibiotics, the
bacterial load was very high. Since this time, we
and others have generalized these findings to many
other inflammatory conditions previously thought
to be sterile including rhinosinusitis, tonsilitis,
Fen Hu, Garth Ehrlich, Christ Post and Hu Ze Li at West China University of the Medical Sciences on the occasion
of Garth being an honorary professor of genetics in October 1999.
FALL 2016
35
adenoiditis, cholesteatoma, sterile loosening of
arthroplasties, chronic nonhealing wounds, bony
nonunion, and many others.
I obtained early tenure at Pitt, an almost
unheard of honor, but less than two years later
Chris convinced me to give it up and join Allegheny
Singer Research Institute, a small private institution
across town. A year latter, Allegheny went into
bankruptcy, but this allowed Chris and I to rebuild
the institute in a manner we thought could advance
good science and medicine.
We had unprecedented freedom for several
years, but not without plenty of angst. There is
nothing like necessity to engender hard work,
and for several years I had more funding from
the National Institute of Deafness and Other
Communication disorders (NIDCD) than any
other investigator in the country. We parlayed this
strength by learning to lobby congress to obtain
infrastructure funding for equipment and facilities
upgrades, and even obtained military funding for
human performance genetic work.
This latter was made possible as Chris and
I had been running a second career in human
disease gene mapping and cloning for the previous
decade. By this time we had been joined by a
remarkable young Chinese Scientist, Fen Hu, who
was instrumental in the transformation of our labs
from standard low throughput molecular biology
approaches to a high throughput genomics facility
that provided us with unprecedented ability to
tackle large-scale problems.
Parallel with our obtaining the first experimental
support for the biofilm paradigm of chronic
infections, I posed the Distributed Genome
Hypothesis (DGH). The DGH began as multiple idea
threads floating in and out of my conscious and
subconscious and slowly coalesced in my mind
over a period of several months, with a series of
observations and experiments.
One of the themes I had been following was that
Rd, a strain of Haemophilus influenzae (Hi), which
was the first free-living organism to be sequenced
by The Institute for Genomic Research (TIGR) in
1995, was missing some of the known virulence
genes from Hi. At first I chalked this up to its having
been in culture for decades, which may have
resulted in artificial selection for rapidly growing
mutants that had deleted genes not necessary for
maximal growth in culture.
To examine this further, Fen constructed dozens
of clone libraries and performed Sanger sequencing
on thousands of clones to take gene content snap
shots of multiple fresh clinical isolates of Hi and
other bacterial pathogens. What we found was
that no matter how deep we sequenced into each
strain’s clone library, 10-15% of the genes were
novel, i.e., never before seen or annotated. This
observation, along with my increasing knowledge
of the mechanisms of horizontal gene transfer and
36
bacterial pathogen genomics, led me to a very
different conclusion regarding what we were seeing.
Haemophilus influenzae, as well as most other
obligate pathogens, has a tiny genome compared
to nonpathogenic bacteria, yet as we discovered,
each strain contained a large percentage of unique
genes. I concluded this must mean, in spite of an
overall mechanism favoring deletion of portions of
the genome over time, these bacteria maintained
a mechanism for uptake and integration of foreign
DNA from the environment.
The possibility of cellular machinery that both
favors deletion and uptake and integration of
novel DNA molecules got me thinking about the
importance of transformation and horizontal gene
transfer in general. At the time, my laboratory was
also working with the pneumococcus and other
pathogens, and I realized all of these diverse
bacterial species have energetic systems, indeed
sometimes multiple such systems, for the uptake of
DNA from the environment. Thus, not only do they
devote significant percentages of their genomes to
encoding DNA uptake and transfer systems, but
also these systems are energetically expensive.
These systems probably would not have survived
over eons of time if they didn’t offer the bacteria
something important in return.
I remembered a course I’d taken from Arnold
Ravin at the University of Chicago in which he
stressed that a single transformation event could
save an entire population from annihilation in
response to the presence of an antibiotic. This
got me re-thinking about the classic experiments
of Frederick Griffith in the 1920’s in which he
discovered transformation in pneumococcus, and
I suddenly realized bacterial transformation was a
meta-virulence trait.
This was the key piece I’d been missing.
Transformation wasn’t merely a rare curiosity
that eventually allowed Oswald Avery and his
colleagues to demonstrate the biological role of
DNA, it was a safe mutagenic mechanism that
facilitated the recombination of already proven
genes – as opposed to point mutations – into a
genome during times of stress, Indeed, these DNA
uptake mechanisms are part of the bacterial SOS
response! Thus, bacteria actually regulate their rate
of mutation in response to the environment.
These many variations in the gene content
among individual bacterial strains in a culture or
a biofilm combine to form a supragenome (also
later termed a pan genome) at the population level
that is of greater size and genetic diversity than
possessed by any one strain of the species. Thus,
bacteria possess both core genes (present in all
strains of a species) and distributed genes (each
present in only a subset of strains of the species).
The constant reshuffling of DNA among bacteria
in a biofilm resulting in the continual creation
of new strains with new genomic character
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
combinations would greatly increase the probability
that at least some of the individual bacteria in
the population would have the right combination
of genes to permit survival and growth as the
environment changes. Thus, in chronic infections,
this supragenome, through horizontal gene transfer,
provides a rapid mechanism for pathogen evolution
and escape from the changing immunological
defenses of a patient or host animal.
I formalized my thoughts as the “distributed
genome hypothesis” as follows:
“Chronic bacterial pathogens utilize a survival
strategy wherein a majority of their genes are
distributed among a population and are not found
in all members of a species; thus there exists
a supragenome at the population level which is
greater than the genome of any one organism.”
The virulence corollary:
“The distribution of genes among a population
serves as a supra-virulence factor that provides
for improved population survival through continual
horizontal gene transfer mechanisms, resulting
in rapid adaptation to environmental conditions
through the reassortment of genes (and alleles).”
At the time I was doing these gedanken
experiments, others demonstrated that horizontal
gene transfer was increased in biofilms relative
to planktonic cultures. This led to my synthesis of
the biofilm paradigm with the distributed genome
hypothesis forming the rubric of “bacterial plurality.”
This embodies the concept that chronic infections
display heterogeneities at many levels—including
phenotype, genotype, and metabolic rate—and that
this heterogeneity, as biological heterogeneities
almost always do, provides the population as a
whole with increased robustness and the ability to
adapt to changing environmental conditions—in this
case the host defense mechanisms.
These observations led to our understanding
there is a fundamental dichotomy between acute
and chronic infections, wherein acute infections are
the result of rapid, clonal, often planktonic growth
which usually can be controlled by antibiotics
and the host’s adaptive immune response, and
chronic infections which form biofilms. The latter
are composed of polyclonal assemblages of
metabolically asynchronous bacterial cells that
can recombine their genetic characters via rapid
energetic methods during the infectious process to
generate diversity, all of which makes them vastly
harder to eradicate.
I quickly realized, however, it would be an
enormous task to comprehensively test these
hypotheses dealing with genomic heterogeneity,
because I would need to perform whole genome
sequencing on large numbers of strains of multiple
species of bacteria in order to fully characterize
their core, distributed, and supragenomes. This was
a daunting task as at that time given there were
exactly two complete bacterial genomes, and each
had taken major labs with nearly unlimited funding
years to generate.
One of my peculiar traits is that I’m a do it
yourself person when it comes to laboratory
science, so it never occurred to me to try to
collaborate with one of the big genome centers. I
have always been a ready and cheerful collaborator
with clinicians and other scientists where ideas are
involved, but when it comes to the data I’m ill at
ease using data generated elsewhere. I like to have
control over the laboratory process.
Between 1999 and 2003 Fen, Chris, and I had
spent more than two million dollars operationalizing
a robotic clone library Sanger sequencing facility,
and Fen was bravely plowing through multiple
strains of Hi, pneumococcus, and Pseudomonas
aeruginosa.
Then lightening struck again when I heard Shaun
Lonergan give a talk on the infant, still largely
nonfunctional, 454 sequencing technology. The
454 Life Sciences Company was looking for an
academic research partner and Shaun invited Fen
and myself out to their facility at the start of 2004
to make a pitch.
One-third of the way through Fen’s presentation
the scientific director got up to get the vice
president, and a few minutes later he, in turn, got
up to get the president. The rest as they say is
history.
They had a technology and wanted it tested by
someone who had a problem that could not be
addressed by existing technology—and we had the
problem. Still it was a major gamble; Fen and I
placed four of our scientific staff on site with 454,
and we essentially moth-balled our multi-million
dollar Sanger sequencing facility that we’d just
spent years building, because we realized that
the operational costs to test distributed genome
hypothesis would bankrupt us.
By mid-2005 we had our own 454 G-20
instrument fully operational and were sequencing
an entire genome every week at a tiny fraction
of the previous cost, but we now had a very
different problem—big data. Sticking to my tried
and true method of relying on lightning strikes, we
happened to have a brilliant young mathematician
in the lab, Justin Hogg. Justin had just graduated
summa cum laude from Pitt and was hired on the
recommendation of my older son, Ian, who was also
a math major.
Justin and I working together—with me asking
the questions and he providing the answers—built
a comprehensive comparative genomic pipeline
which we still use a decade later. True to form,
before this project neither of us had any training or
background in bioinformatics. Justin first-authored
our first major paper in comparative bacterial
genomics because not only did he build the
software pipeline, but he also developed a very
powerful mathematical tool to rapidly estimate the
parameters of any species’ supragenome.
Finally, in what is perhaps my favorite paper, we
were able to complete the circle and find clinical
proof of distributed genome hypothesis by following
a pediatric case in which the child suffered from
chronic and recurrent pneumococcal infections. I
gave Fen clinical data on a large group of children
who had been followed longitudinally and for whom
there were serial pneumococcal isolates available
that had already been serotyped and subjected to
a DNA fingerprinting method termed multi-locus
sequence typing (MLST).
Among this group, Fen identified one patient who
had different serotypes at different times, but where
the original serotype would re-appear, but now with
a different MLST type—suggesting horizontal gene
transfer. We performed whole genome sequencing
on each of the recovered strains and my postdoc
Luisa Hiller found a major lineage that had
undergone more than two dozen transformation
events leading to replacement of approximately
eight percent of the genome over a seven month
period! So much for glacial rates of evolution. We
published this work in PLoS Pathogens in 2010.
The huge effort we put into developing next
generation sequencing paid numerous dividends
beyond my being able to test and prove the
distributed genome hypothesis. We used this
technology in combination with the whole genome
amplification technology that had been developed
by one of my faculty colleagues, Roger Lasken, to
perform the first sequencing of an unculturable
bacterium, the marine filamentous Beggiatoa.
In collaboration with colleagues at the Max
Plank Institute for Marine Microbiology in Bremen
Germany, we discovered Beggiatoa was an ancient
fusion of a cyanobacterium and a proteobacterium;
this also explained why it had three membranes
instead of two. Using a similar approach, we worked
with scientists at the Chinese Academy of Sciences
to characterize the genome of a Yak gut bacterium
associated with the breakdown of cellulose as part
of a waste cellulose biofuels project I had initiated.
The comparative genomics pipeline we had
developed to gather data for a horizontal test of
the distributed genome hypothesis was also put
to use in characterizing numerous nonpathogenic
bacterial species. These studies indicate many, if
not all, bacterial species possess a supragenome
regardless of their ecological niche.
This same computational system also allowed
us to demonstrate numerous mistakes in the
classical taxonomy of various groups of bacteria.
For example, bacteria historically placed in a genus
called Shigella actually arose independently within
the species Escherichia coli at least three times
by acquisition of shiga toxin genes—the latter are
polyphyletic. There is no genus Shigella.
Similarly, Bacillus anthracis (the cause of
anthrax) is not a species, it is clade within B. cereus
that has acquired toxin genes. These two Bacillus
“species” have essentially identical core genomes.
It’s not always the splitters, however, who are
wrong. The lumpers come in for their lumps as
well. We have shown that Gardnerella vaginalis
(associated with bacterial vaginosis) is a genus
composed of at least four and perhaps twice that
many species. Our work in comparative genomics
has demonstrated the core genome can be used
to define a species such that after the core has
reached its asymptote, any strain that significantly
reduces the core genome size belongs to another
taxonomic group.
In 2013, with the Allegheny Health System again
staring bankruptcy in the face, I decided to finally
move on and I accepted a professorship at Drexel
University College of Medicine in the microbiology
and immunology department. This position has
finally brought me back to retroviral research
working with my chair, Brian Wigdahl, designing
patient-specific proviral sequencing strategies
on our new 3rd generation Pacbio sequencer for
CRISPR-cas-based excision.
In addition, I am starting the Center for Advanced
Microbial Processing (CAMP) to exploit the
technologies we developed for rapidly identifying,
isolating, and cloning specific DNA sequences
to “mine” commercially important biosynthetic
pathways from the microbial dark matter. This
idea came out of a joint project we had done with
David Sherman’s lab at the University of Michigan
in which my graduate student, Ben Janto, had
used hologenome (whole genome sequencing of
a metazoan and its microbiome) sequencing of a
tunicate to identify a biosynthetic pathway in what
turned out to be an endosymbiotic bacteria that
was responsible for the synthesis of an approved
anti-cancer drug that was fantastically difficult
and expensive to make using synthetic chemical
approaches.
With CAMP our approach is based on starting
with mixed populations of microbes, and without
using culture, identifying and purifying the species
of biosynthetic interest using 16S rRNA fluorescent
in situ hybridization-based fluorescence-activated
cell sorting to obtain small populations of the
target species for subsequent whole genome
amplification and whole genome sequencing. The
DNA sequence is then bioinformatically parsed to
identify the biocatalytic pathways of interest, which
are then cloned and re-engineered for expression
in genetically tractable species for the fermentative
production of commercially and medically
important biomolecules.
It is estimated that biosynthetic production of
chemicals over the next 25 years will mirror the
FALL 2016
37
Garth Ehrlich, Peter Nara, Bill Costerton, Pat DeMeo and Chris Post at the festschrift in honor of Bill Costerton, February 2012.
rise of compounds produced via synthetic organic
chemistry during the middle part of the last century.
One of the highlights of my career was the
friendship I developed with Bill Costerton, which
led ultimately to his joining our group at ASRI in
2008. By that time he had already reinforced the
concepts of big thinking and courageous scientific
stances, and had given me numerous forums at
national and international meetings to present
my theoretical musings on chronic bacterial
pathogenesis. Bill remained with us bringing his
biofilm vision to orthopedic practitioners around the
world until he died from pancreatic cancer in 2012.
In my mind, Bill is the most important
microbiologist of the last half century. A Canadian
by birth, he was a member of the Royal Society
of London, was ISI’s most cited microbiologist for
years, and published over 700 papers. However, he
is best known as the person who articulated the
biofilm mode of bacterial growth.
He was a force of nature with an energy and
spirit that cannot be described to those who didn’t
know him; even in his late 70’s no postdoc could
38
hope to keep up with him. Following his diagnosis,
Chris and I hurriedly organized a festschrift for
him and invited microbial luminaries from around
the world to join us in honoring him. Although it
was done in a hurry and held in the dead of a
Pittsburgh winter, we did not have a single invited
scientist demur. Every continent was accounted for.
When I visited Bill on his deathbed days
before he passed, his personality was completely
unchanged, and he spent the first several hours
giving me a list of things he wanted me to finish up.
Chief among these was the posthumous publication
of a book we had been working on together in his
biofilm series with Springer on culture negative
orthopedic infections. If I have half the grace that
Bill did when my time is up, I will be proud.
In 2014, I was elected a fellow of the American
Association for the Advancement of Science
principally for my work on the construction of the
various components of bacterial plurality, and my
seminal role in developing the field of molecular
diagnostics.
Along the way, I also have had successes in
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
human genetics, mapping and cloning multiple
skeletal and gastrointestinal disease genes, and
modeling how the mutant alleles produce their
pathology. These works have lead to multiple highly
cited papers in Nature Genetics and other frontline
journals.
What is most interesting about all of these
fields is that I have no formal training in any of
them, rather it was because the mentors I had
in Syracuse believed in me. John and Bernie,
by trusting and relying on me, had instilled my
confidence to tackle any problem; I have always
felt that since I had a doctor of philosophy I could
pursue any area of science that interested me. I am
now pursuing a bacterial etiology for Alzheimer’s
disease. When I’m not worrying about the next big
thing, it will be time to retire.
Graduate Student News
and Achievements
Ph.D. student Liz Droge-Young
(Pitnick lab) had her recent
publication in Behavioral Ecology
covered by Syracuse University
News. Her research suggests that the
desiccating environment of stored
grain facilities underlies the evolution
of extreme promiscuity by female red
flour beetles, with females mating
with many males each day to harvest
moisture from their ejaculates. In
something of a sexual conflict twist,
all of this mating appears to come at
a cost to males. A profile of Liz and
her research is included in this issue
of BIO@SU.
Ph.D. student Mason Heberling
(Fridley lab) was awarded the 2015
Alexander Gourevitch Memorial
Award, the Department of Biology’s
highest graduate student award, and
an Outstanding Dissertation Award
from the College of Arts and Sciences
for the 2014-15 academic year.
Ph.D. student Elise Hinman (Fridley
lab) was awarded a National Science
Foundation Doctoral Dissertation
Improvement Grant.
Ph.D. student In Su Jo (Frank lab)
received the 2015 Ecological Society
of America Asian Ecology Section
Outstanding Graduate Student Award.
Ph.D. student Kelsey Martinez
(Fridley lab) was awarded an East
Asia and Pacific Summer Institutes
for U.S. Graduate Students grant from
the National Science Foundation to
support her research in Japan during
summer 2016.
Ph.D. student Caitlin McDonough
(Pitnick/Dorus lab) was awarded
a National Science Foundation
Graduate Research Fellowship.
Ph. D. students Caitlin McDonough
and Emma Whittington, along with
Scott Pitnick and Steve Dorus, had a
review paper accepted for publication
in the Journal of Proteomics. The
paper is entitled “Male and female
reproductive system proteomics:
elucidating the molecular basis of
postmating/prezygotic reproductive
barriers.”
Ph.D. student Luka Negoita (Fridley
lab) was awarded a National Science
Foundation Doctoral Dissertation
Improvement Grant.
Ph.D. student Jeremy Sloane
(science teaching, Wiles lab) won the
Carlock Award for Graduate Student
Research at the 2015 National
Conference of the Association for
College and University Biology
Educators.
M.S. student Kelly Schmid (Friedman
lab) won the Best Poster Award at
the Syracuse University All-University
Graduate Research Symposium.
Ph.D. student Emma Whittington,
along with Steve Dorus, postdoctoral
researcher Kirill Borziak, and Qian
Zhao (a visiting scholar from
Chonqing University, China), had
their research published in Insect
Biochemistry and Molecular Biology
as part of a special issue on
biological insights from the Manduca
sexta genome. The paper is entitled
“Characterisation of the Manduca
sexta sperm proteome: Genetic
novelty underlying sperm composition
in Lepidoptera.” Emma was also
awarded a Syracuse University
Graduate Fellowship for the spring
2016 semester.
The following students
have completed their
master’s theses in
2014-2015:
Hannah Blair
Thesis: “Impacts of Ship Noise on
the Nighttime Foraging Behaviors of
the North Atlantic Humpback Whale
(Megaptera novaeangliae)’’
Advisor: Susan Parks
Hannah is a Ph.D. student at Stony
Brook University.
Elisabeth (Carpenter) Bodnaruk
Thesis: “Foraging in Fractals? A
Deductive Test of Two Mechanistic
Community Assembly Models”
Advisor: Mark Ritchie
Jessica McCordic
Thesis: “Discrimination of Age, Sex,
and Individual Identity Using the
Upcall of the North Atlantic Right
Whale (Eubalaena glacialis)”
Advisor: Susan Parks
Jessica is an educational outreach
coordinator for the Pacific Whale
Foundation in Hawaii.
The following students
have completed their
doctorial dissertations in
2014-2015
Nikhilesh Dhar
Dissertation: “Characterization of
Two Arabidopsis Genes Involved in
Regulating Defense and Flowering”
Advisor: Ramesh Raina
J. Mason Heberling
Dissertation: “Functional Traits and
Resource-Use Strategies of Native
and Invasive Plants in Eastern North
American Forests”
Advisor: Jason Fridley
Mason is a postdoctoral research
associate at the University of
Tennessee-Knoxville.
In Su Jo
Dissertation: “Effects of Plant
Invasions on Ecosystem Processes:
Linking Above- and Below-ground
Resource-use Strategies of Native
and Invasive Species in Eastern U.S.
Forests”
Advisor: Doug Frank
In Su is a postdoctoral research
associate at Purdue University.
Megan McSherry
Dissertation: “Human-Managed vs.
Natural Grazing Systems: Exploring
Effects of Livestock and Wildlife
Grazing at Multiple Scales”
Advisor: Mark Ritchie
Megan is a postdoctoral research
associate at Princeton University.
Elijah Carter, M.S., Biology and
Ph.D., College Science Teaching
Dissertation: “Students’ Attitudes
towards Socially – but Not
Scientifically – Controversial
Subjects: Evaluating Ways in which
These Attitudes May Be Shifted”
Advisor: Jason Wiles
Elijah is a postdoc in the Drake Lab
at the University of Georgia
FALL 2016
39
Undergraduate Activities and Achievements
THE UNDERGRADUATE CLASS OF 2015
Degrees in biology, biochemistry, or biotechnology
were awarded to 159 undergraduates in May 2015.
Each spring before graduation, the Department
of Biology celebrates the achievements of our
graduating students on Senior Honors Day. Fifty-six
students were recognized for academic excellence,
research accomplishments, or excellence in both
academics and research. Nineteen seniors earned
degrees with distinction in recognition of their
successful completion of a high-quality research
thesis. These students are indicated by an asterisk.
ACADEMIC ACHIEVEMENT: Katherine L. Driscoll,
Angela L.J. Italia, Huiwen Jiang, Eleonora
Koshchak, Alexander J. Liucci, Julia M. Pratt,
Shahpara A. Shamsi, Shaylyn C. Tuite, Qi Y. Wu.
RESEARCH ACHIEVEMENT: Karina I. Acevedo,
Stephen O. Ajayi, Isidore Amani, Katherine M.
Bunch,* Luis A. Castelan,* Tricia A. Daniels,
Tomas R. Daviu,* Trey A. Dix, Will T. Fancher,
Ria S. Foye-Edwards, Tricia L. Honors, Sarah
Hosie,* Gina Kim,* Kristofer D. Medina, Emily
N. Mongeon, Berlini Narampanawe, Nicholas C.
Palmateer,* Adrienne M. Parsons,* Jocelyn M.
Rodriguez, Christian E. Rosado, Marquerite A.M.
Smith, Ryan K. Ullrich, Grace K. Vallejo,* Leslie D.
Walters, Jennifer H. Yoon.
RESEARCH AND SCHOLARSHIP: Megan T.
Baron,* Margaret A. Blasi,* Rachael M. Burke,
Jeff Darkwa, Justin N. Elkhechen,* Caroline A.
Habjan, Martin R. Hehir, Domonique A. Jackson,
Reed W. Kamyszek, Sam K. Lauffer,* Elizabeth
A. McMahon, Kristopher S. Murray,* Daniel
D. Nguyen, Bhakti Y. Patel, Leslie M. Patton,*
Sebastian T. Perdomo, Natalie Rebeyev,* Elliott J.
Russell, Megala D. Sankrith,* Tyler J. Schapero.
The following are special Department of Biology
awards enabled by generous gifts from members of
the Biology Advisory Board. The awards recognize
outstanding scholarship and research by students
in each of the three undergraduate degree
programs that the department offers.
OUTSTANDING ACHIEVEMENT IN BIOLOGY –
DONALD G. LUNDGREN MEMORIAL AWARD: This
recognizes outstanding scholarship and research
in biology. This year’s awardee was Kristin Weeks,
whose research was conducted with Professor Mark
Ritchie. Kristin was awarded a distinction in biology,
40
was named a Syracuse University Scholar, and
received her degree with honors from the Renée
Crown University Honors Program.
OUTSTANDING ACHIEVEMENT IN BIOCHEMISTRY:
Komal S. Safdar. Komal conducted research with
Professor Eleanor Maine. A profile of Komal and her
research is included in this issue of BIO@SU.
OUTSTANDING ACHIEVEMENT IN
BIOTECHNOLOGY: Luke Strauskulage. Luke
conducted research with Professor Ramesh Raina
and was awarded a biotechnology degree with
distinction. A profile of Luke and his research is
included in this issue of BIO@SU.
UNIVERSITY HONORS: The following biology/
biochemistry students were awarded degrees with
honors from the Renée Crown University Honors
Program. An honors degree requires completion
of honors courses and extracurricular activities
stressing academics, global awareness, civic
engagement, collaboration, and command of
language. Students must also complete and
defend a capstone project. Those indicated by an
asterisk were also awarded a distinction in biology,
biotechnology, or biochemistry.
Katherine Marie Bunch,* Luis Angel Castelan,*
Justin N. Elkhechen,* Caroline Ann Habjan, Sarah
Hosie,* Gina Kim,* Elizabeth Ann McMahon,
Kristopher Sean Murray,* Adrienne Marie
Parsons,* Bhakti Y. Patel, Natalie Rebeyev,*
Elliot John Russell, Megala Devi Sankrith,* Luke
Strauskulage,* Kristin S. Weeks.*
PHI BETA KAPPA: Sam Kendrick Lauffer
OTHER UNIVERSITY AND COLLEGE AWARDS:
DOOLEY ORNSTEIN REISMAN, ROBERT CHARLES
ORNSTEIN, AND LT. ADOLPH ORNSTIEN AWARD:
Justin N. Elkhechan, Kristopher Sean Murray,
Natalie Rebeyev, Kristin S. Weeks. ASTRONAUT
SCHOLARSHIP: Luke Strauskulage. BARRY
GOLDWATER SCHOLARSHIP: Luke Strauskulage.
BECKMAN SCHOLAR: Rachael M. Burke. GATES
CAMBRIDGE SCHOLARSHIP: Natalie Rebeyev.
NATIONAL SCIENCE FOUNDATION GRADUATE
RESEARCH FELLOWSHIP: Kristopher Sean Murray.
LOIS AND MARTIN J. WHITMAN SCHOLAR: Luis
Angel Castelan. UNDERGRADUATE BLACK AND
HISPANIC SCHOLAR: Luis Angel Castelan.
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
SYRACUSE UNIVERSITY SCHOLARS: Designation
as a Syracuse University Scholar is the highest
academic honor bestowed at the University. Twelve
graduating seniors were named SU Scholars at
the May 9, 2015, commencement. These included
biology or biotechnology students Elizabeth Ann
McMahon, Natalie Rebeyev, Elliott John Russell,
and Kristin S. Weeks. Their achievements and
activities as described in SU NEWS when they were
students are as follows:
Elizabeth McMahon is bright and dedicated,
a Coronat Scholar and a Renée Crown Honors
Program student with a biology and policy studies
double major. Her goal is to complete a master’s
of public health and global medicine and then
attend medical school, focusing on working with
underserved communities around the world. Her
capstone thesis is a collaboration with researchers
at SUNY Upstate Medical University to carry out
laboratory work and field studies in Ecuador
involving the mosquito-borne disease dengue fever.
She has studied abroad with the Global Health
and Tropical Medicine program in Costa Rica and
worked with the Global Brigade helping provide
medical care to citizens of poor, remote villages
in Honduras. Working with Syracuse city planners,
Elizabeth developed a program for Syracuse
University Recreation Services in which students,
using a GPS program, take the Connective Corridor
bus downtown, partake in team-building activities
and explore the city. She is working with a group
aiming to expand the GPS program to be used as
part of SU Abroad orientations. She has also done
volunteer work through the International Youth
Scholars program with refugees from Somalia and
the Congo, and immigrants from the Middle East in
the Syracuse area. In addition, she has volunteered
at Upstate University Hospital, Habitat for Humanity
and Ronald McDonald House.
Natalie Rebeyev graduated from the College of Arts
and Sciences with majors in biology and modern
Jewish studies. She is a Coronat, Remembrance,
McNair, and past ARISE CSTEP Scholar and a
member of the Renée Crown University Honors
Program. She won a Research and Scholarship
Award from the Department of Biology, where she
completed her capstone honors thesis, “Defining
the Role of Erlin2, an ER Membrane Protein of the
SPHF1/2 Complex That Mediates Ubiquitination
of the Inositol Triphosphate Receptor (IP3R1) and
Cell Autophagy,” with Richard Wojcikiewicz at
SUNY Upstate Medical University. She took the
initiative in finding a research mentor at SUNY
Upstate and spent eight months in Juntao Luo’s
lab studying nano-medicine and drug delivery.
After attending a lecture by Nobel Laureate
Aaron Ciechanover, Natalie approached him
for a research position and spent the summer
conducting cancer research in his colleague
Amir Orian’s lab at the Technion Institute in Israel
and continued her research in Wojcikiewicz’s
lab. Additionally, she volunteers as a “Peds Pal”
at SUNY Upstate, tutoring pediatric oncology
students, and is a peer advisor and tutor for both
biology and chemistry. She plans to pursue a
career in oncology as a biomedical researcher/
physician. She was awarded a Gates-Cambridge
Scholarship to pursue a Ph.D. in medical science
and immunology at the Cambridge Institute for
Medical Research, England.
Elliott Russell, a member of the Renée Crown
University Honors Program, will graduate
with majors in biomedical engineering and
biotechnology and will attend the Northwestern
University Feinberg School of Medicine. Along
with providing direct health care, he hopes to
develop novel techniques and devices for the
administration of health care. His integration
of engineering research and development with
entrepreneurial vision inspired him to found
two companies: Blue Defibrillation focuses on
increasing the accessibility and affordability of
automated external defibrillators (AED), and
Apollo Biomedical is focused on the development
of a smart knee brace to better assist individuals
recovering from serious injuries. His honors
capstone project focused on developing the
technology required to transform a smartphone into
the control system for a mobile AED. After studying
abroad in Dublin, Elliott traveled to Nicaragua for
nine weeks to repair medical equipment in rural
hospitals. He worked in the post-anesthesia care
unit at Mary Greeley Medical Center in Iowa and
at Iowa State University developing Meta!Blast, an
educational video game designed to teach students
cell biology. His undergraduate research developed
and incorporated a graphic user interface into
automatic contour‐based tracking for in-vitro
environments (ACTIVE) cell tracking software.
In Syracuse, Elliott has been involved in the
Engineering Ambassador program and volunteering
at the Veterans Affairs Medical Center. He worked to
start a Syracuse University chapter of Engineering
World Health, the organization through which he
spent time in Nicaragua. He was president and co‐
founder of Syracuse University’s Pre‐Health Honors
Society and served as a global ambassador for SU
Abroad.
UNDERGRADUATE:
Biochemistry and Anthropology major José Marrero-Rosado ’17 (Lewis lab) has been awarded a
two-year Greater Research Opportunity (GRO) Undergraduate Fellowship from the Environmental
Protection Agency. This award of $50,000 includes contributions toward his tuition and living costs
and money for his research project. The award also included a three-month paid internship during
summer 2016 in an EPA research laboratory. At Syracuse University, Marrero-Rosado’s fellowship
will support his honors research project with Professor Kate Lewis investigating the toxicity of two
hydrophobic poly-aromatic hydrocarbons isolated from Onondaga Lake on zebrafish and frog
embryos. He has been awarded a Remembrance Scholarship and is a McNair Scholar. In addition,
he chairs the Student Life Committee of the Syracuse University Senate, serves as a student
representative on the Syracuse University Board of Trustees, and serves on the Division of Student
Affairs’ Student Advisory Board. During summer 2015, his research in the Lewis lab was supported
by a fellowship from the Louis Stokes Alliances for Minority Participation (LSAMP). Marrero-Rosado
won first place in the Biological Science category for his poster exhibited in the Syracuse University
Summer Symposium for Undergraduate Research in August 2015.
Kristin Weeks was a Senior Class Marshal for
Arts and Sciences. She completed triple majors
in biology, sociology, and political science. She
has pursued internships in Scotland, Zambia,
and Florence. She has conducted substantial
research in biology, sociology, and political science,
specializing in issues related to global warming,
climate change, and HIV/AIDS. Kristin conducted
research in ecology; developed her research
literature, theory, and question independently; and
carried out five greenhouse experiments and a field
study independently. She expanded her field study
(on land degradation and fires in a developing
country) into political science research and spent
a year and a-half examining global governance
structures that fund environmental conversation
projects in the developing world. As a chef for
Ronald McDonald House, Kristin helps make a
temporary home feel familiar and talks to people
overwhelmed by the hospitalization of their child/
family member. As a founding member of the Renée
Crown Honors Advisory Board, a TA, and a tutor, she
enhanced the sense of community in the honors
program and the sense of support at Syracuse
University. She has also been a mentor in the
violence prevention program on campus.
CLASS MARSHAL: Kristin S. Weeks was selected
to serve as a college marshal for the 2015 College
of Arts and Sciences Convocation.
CORONAT SCHOLARS: Syracuse University invites
superbly accomplished incoming freshmen
interested in the liberal arts to enter the Coronat
Scholars Program, which includes full tuition for
four years, funding for study abroad, support for
research, advanced study, volunteer work, and
admission to the Renée Crown University Honors
Program. Biology/biotechnology students Elizabeth
Ann McMahon, Natalie Rebeyev, Elliot John
Russell, and Kristin S. Weeks were among seniors
recognized for completing this program.
REMEMBRANCE SHOLARSHIPS: Each year
Syracuse University awards 35 scholarships in
memory of the 35 Syracuse University students
lost in the bombing of Pan Am Flight 103 over
Lockerbie, Scotland, December 21, 1988.
The scholarships are awarded on the basis of
distinguished academic achievement, citizenship,
and service to the community. Scholarships for
2014-15 were awarded to biology/biotechnology
students Elizabeth Ann McMahon, Natalie
Rebeyev, Elliott John Russell, and Kristin S.
Weeks.
FALL 2016
41
Other Undergraduate Awards and
Achievements
UNDERGRADUATE RESEARCH PROJECTS AND
SCHOLARSHIPS: The Department of Biology has
a historic commitment to involving students in
faculty-mentored research that began almost a
century ago. While the number fluctuates from
semester to semester, we know that more than
100 students are annually engaged in such
research through opportunities in biology, in
other departments in Arts and Sciences, at SUNY
Upstate Medical University, at SUNY ESF, and at
other schools and colleges. Many of these students
presented their research projects as posters or talks
at the annual Undergraduate Research Conference
April 24, 2015.
In summer 2015, the following undergraduates
were granted awards in support of research in
the laboratories of biology faculty. These students
and their mentors include Snigdha Chatterjee
(Raina), Maria Dombrov (Coleman), Jake
Goldsmith (Pitnick), Margo Malone (Segraves), Joe
Petraccione (Parks), Genevieve Pilch (Friedman),
Liz Reynolds (Korol), Kelsey Schuch (J. Hewett),
Jessica Toothaker (Pepling), and Christiane Voufo
(Lewis). In addition, Courtney Rosser (S. Hewett)
and Alicia Warnecke (J. Hewett) received summer
support from the Neuroscience Program.
CROWN-WISE AND LYNNE PARKER SCHOLAR
AWARDS: The Renée Crown Honors Program
awards competitive grants to aid students in
completing their capstone projects. Those receiving
these grants are recognized as Crown/Wise or
Lynne Parker Scholars. Scholars for fall 2014
include biology, biochemistry or biotechnology
majors Justin Elkhechen, Gina Kim, Elizabeth
McMahon, and Leslie Patton and for spring 2015
Adrian Alvarez, Alexandria Aruck, Miriam Bhatti,
Alexandra Chapman, Micheline Laing, Pristine
Mei, Marilyn Nishiguchi (Lynne Parker Scholar),
and Robert Swanda.
The department acknowledges and thanks the
generous and vitally important support of the
following funding sources for these students:
Korczynski-Lundgren Undergraduate Summer
Research Fund, Levy-Daouk Fund, Phillips
Undergraduate Research Fund, and the iLearn
fund of the College of Arts and Sciences.
Undergraduate Research Conference
The 20th annual Undergraduate Research Conference, in conjunction
with the Senior Award Ceremony and a poster session, was held April 24,
2015, in the atrium of the Life Sciences Complex. Posters describing 38
projects and involving 44 undergraduate students were presented. Topics
reflected the diversity of opportunities available for undergraduate research
available at Syracuse University and neighboring academic institutions.
Studies included transcription factors in interneuron specification, effects
of temperature on mating in yeast, sperm competition in fruit flies and
flour beetles, regulation of pathogen defense in plants, and toxicity of
contaminants from Onondaga Lake on zebrafish embryos. Mentors for
the student participants this year included professors Heather Coleman,
Scott Erdman, Thomas Fondy, Jannice Friedman, Sarah Hall, James Hewett,
Sandra Hewett, Kate Lewis, Eleanor Maine, Melissa Pepling, Scott Pitnick,
Ramesh Raina, Mark Ritchie, and Kari Segraves from the Department
of Biology; Robert Doyle from the Department of Chemistry; and James
Henderson from the Department of Biomedical and Chemical Engineering.
Mentors also included Jeffrey Amack and Guirong Wang from SUNY
Upstate Medical University.
42
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
Faculty News
David Althoff was awarded a grant from the National Geographic
Society to search for hidden species diversity in yuccas and
yucca moths.
David Althoff and Kari Segraves were awarded a grant from the
National Science Foundation to re-evaluate the importance of
mutualism vs. antagonism in the well-known interactions of yucca
plants and yucca moths.
John Belote and Scott Pitnick, along with postdoctoral fellow
Nalini Puniamoorthy and Ph.D. student Brian Gress, traveled to
England in September 2015 for the 13th Biennial Biology of
Spermatozoa Conference, where Nalini was one of five plenary
speakers and Brian gave a poster presentation.
Carlos Castañeda was awarded the ORAU Ralph E. Powe Junior
Faculty Enhancement Award.
Steve Dorus presented an invited seminar as part of an Honorary
Symposium for Professor Wolfgang Epstein at the University of
Osnabrück (Germany) entitled “The KdpD/KdpE Two-Component
System: Integrating K+ Homeostasis and Virulence.”
Scott Erdman completed six years as associate chair and
director of undergraduate studies. He also recently attended the
2016 Northeast Regional Yeast Meeting held at SUNY Buffalo.
the Marine Biology Laboratory in neuroscience. Along with his
collaborator, Torsten Wöllert (research assistant professor of
biology), he presented a poster on candidiasis at the annual
meeting of the American Society for Cell Biology in San Diego.
Kate Lewis gave invited seminars at the Department of
Embryology at the Carnegie Institute of Washington, the University
of Vermont, and Drexel University.
Eleanor Maine’s NIH R15 grant has been funded.
Susan Parks obtained new funding from the National Park
Service, the National Geographic Society, and the Marine
Mammal Commission to support research led by graduate
student Leanna Matthews to study the effects of humangenerated noise on the underwater behavior of harbor seals in
California, Oregon, and Glacier Bay National Park and Preserve
in Alaska. Susan also organized a special session at the
100th Ecological Society of America meeting in Baltimore in
August 2015, entitled “Ecological Acoustics: Conceptual and
Technological Advances in Ecology Through Sound.” She also
gave invited talks at two international meetings: the Watkins
Memorial Marine Mammal Bioacoustics Symposium in New
Bedford, Massachusetts, in March 2015, and the International
Bioacoustics Congress in Murnau, Germany, in September 2015.
Melissa Pepling has been promoted to full professor.
Jason Fridley attended the Ecological Society of America Annual
Meeting in Fort Lauderdale, Florida, in August; it was hot. He
also traveled to Stockholm in June to serve as an external Ph.D.
examiner and then to northern England for his annual fieldwork
there.
Sarah Hall’s National Institutes of Health R15 grant has been
funded.
Sandra Hewett’s NIH/DHHS R21 grant has been funded.
Sandra Hewett and Kate Lewis are among a group of colleagues
who were awarded another New York State contract for spinal
cord research.
George Langford, dean emeritus of the College of Arts and
Sciences and Distinguished Professor of Neuroscience and
professor of biology, spent the past year on sabbatical, dividing
his time between the Marine Biological Research Laboratories at
Woods Hole, Massachusetts, and the Howard Hughes Medical
Institute in Chevy Chase, Maryland. During this time he continued
his research into how molecular motors that traffic cellular cargo
via the cytoskeleton may be important to understanding agerelated cell death in neuronal tissues. While at HHMI, he spent a
substantial portion of his time working with its Science Education
and Research Training Program that is helping to develop new
approaches to teaching introductory science at the college level.
He also spent significant time there investigating what specific
aspects of the most successful programs supporting the retention
and development of underrepresented minority students in the
sciences lead to their exceptional track records. In addition to
this work, he continued his involvement with several foundation
boards, including the Burroughs Wellcome Fund and The Grass
Foundation, the latter of which is aligned with ongoing work of
Scott Pitnick’s Animal Behavior class (BIO 417) published class
research in the British journal Behaviour with 19 undergraduate
student co-authors.
Ramesh Raina was the recipient of the 2016 Wasserstrom Prize
for Graduate Teaching from the College of Arts and Sciences.
Ramesh Raina’s and Mark Ritchie’s National Science
Foundation grant has been funded.
Kari Segraves was the inaugural winner of the Center for
Fellowship and Scholarship Advising’s (CFSA) Mentor of the Year
award in April 2016. Kari also gave an invited colloquium talk at
the Botanical Society of America meetings in Edmonton, Alberta,
Canada, and published papers in Animal Behavior, Proceedings
of the Royal Society of London, and American Naturalist on her
studies of mating behavior, speciation, insect divergence, and
coevolution.
Jason Wiles was awarded a grant, Enhancing Recruitment
and Retention of Underrepresented Populations Through PLTL
(ERRUPT) from the National Science Foundation for $169,734.
A second grant proposal to NSF with John Tillotson (science
teaching) has also been recommended for funding.
Faculty members John Belote, Steve Dorus, Jannice Friedman,
and Scott Pitnick have recently formed a collaborative group –
the Center for Reproductive Evolution (CRE). The center’s website
is www.cre.syr.edu. Some of the CRE research that relates to
genotype-phenotype associations in Drosophila is empowered by
OrangeGrid, Syracuse University’s newly developed computational
infrastructure.
FALL 2016
43
Who, What, When, Where
Alumni
IN MEMORIAM:
Joseph S. Galati B.S. ’81 is the medical
director of the Center for Liver Disease
and Transplantation at Houston Methodist
Hospital in Houston.
John Badgerow Ph.D. ’84 (with Reed
Hainsworth) died February 12, 2015, in
Kalamazoo, Michigan, after a long struggle
with bladder cancer.
Russell Tracy Ph.D. ’79 (with Sam Chan),
professor of pathology and laboratory
medicine at the University of Vermont
College of Medicine, was awarded the
Distinguished Scientist designation by the
American Heart Association/American
Stroke Association at the AHA 2015
Scientific Session in Orlando, Florida, in
November 2015.
Marilyn S. Kerr, assistant professor
of biology and founder of the Health
Professions Advising Program on campus,
died peacefully October 6, 2016 in
Syracuse, NY at the age of 82. An
appreciation of Marilyn’s many important
contributions to the department, college
and university will be provided in the next
issue of BIO@SU. Marilyn very generously
gifted funds to establish an endowed
graduate scholarship in the biology
department. Alumni who wish to make
a memorial contribution to the “Marilyn
Sue Kerr Graduate Scholarship Endowed
Fund” may do so by making their check
payable to “Syracuse University” and
mailing to the attention of Karen Weiss
Jones, Assistant Dean for Advancement,
College of Arts and Sciences, 312 Hall
PLEASE SEND UPDATES ON YOUR
ACTIVITIES TO:
[email protected] or
Ernest Hemphill
Room 114
Life Sciences Complex
107 College Place
Syracuse NY 13244
44
THE DEPARTMENT OF BIOLOGY AT SYRACUSE UNIVERSITY
of Languages, Syracuse, NY 13244.
Questions? email [email protected].
More information about Marilyn’s many
accomplishments, and recollections from
some of the numerous people whose
lives she touched, can be found in the
following remembrance: asnews.syr.edu/
newsevents_2016/releases/marilyn_
kerr_tribute.html
Jeffrey Kovatch, Ph.D. ’08 passed away on
November 5, 2016 due to complications
arising from a brain aneurysm he suffered.
Jeff was an associate professor of biology
at Marshall University in West Virginia.
Jeff’s dissertation adviser at Syracuse
was F. Reed Hainsworth. Jeff is survived
by his wife Paige Muellerleile and two
daughters Jada, 10 and Chelsea, 4. For
those interested, donations to help Jeff’s
family defray medical care costs can be
made through You Caring www.youcaring.
com/support-paige-muellerleile-and-jeffkovatch-674225.
GIVINGTO
BIOLOGY
AT SU:
I
n this issue of BIO@SU we are continuing our appeal to our many alumni and friends for your help in supporting the
programs of the Department of Biology. Whether you donate regularly to SU or are considering a first-time gift, we hope
that you will consider designating your contribution to support biology at SU. Your support will directly benefit the quality
of our teaching programs and research.
Our needs are diverse and encompass all aspects of our program, so we have decided to concentrate our efforts on three
areas. Your donation to the Biology Gift Fund can be designated for use in one of the following ways.
Emeritus Chairs Program
Honors the efforts of previous Biology Department Chairs John M. Russell, H. Richard Levy, David Sullivan, and Judith
Foster, and provides the Biology Department chair with flexibility to meet critical needs, such as one-time purchases of
major scientific equipment, support for new course development, and rewarding outstanding achievements of biology
faculty and instructors in teaching and research.
Undergraduate Programs
Supports opportunities for undergraduates to participate in field study and unique research opportunities in class,
with faculty members, and summer research projects. Supports improvements in undergraduate teaching facilities and
equipment in laboratories, independent research opportunities, travel to research meetings, and the development of new
courses addressing the most contemporary issues in biology.
Graduate Programs
Supports opportunities for graduate students to travel to national and international meetings, and to participate in
advanced courses at major research facilities, and rewards outstanding students in the program with research fellowships.
With your help, we can ensure that biology faculty and students have the resources they need to excel. Your support will be
greatly appreciated, either by phone: 888-CAS-ALUM (888.227.2586) or online: givetothecollege.syr.edu (under “I would like to
give to,” scroll down to “Biology Discretionary Fund” and enter the dollar amount of your gift).
For more information about giving to the Department of Biology in the College of Arts and Sciences, contact
Karen Weiss Jones, assistant dean, advancement, at 315.443.2028 or [email protected].
FALL 2016
45
SYRACUSE UNIVERSITY
Department of Biology
Life Sciences Complex
107 College Place
Syracuse, NY 13244
The Undergraduate Research Conference
NONPROFIT ORG.
U.S. POSTAGE
PAID
SYRACUSE UNIVERSITY,
SYRACUSE NY