PhD in Integrative and Systems Biology Program

Facilities and Other Resources
University of Colorado Denver
The University of Colorado Denver|Anschutz Medical Campus is the state’s number one research-funded
university, offering comprehensive programs for undergraduate, graduate and health sciences students on two
campuses—in downtown Denver and on the Anschutz Medical Campus in Aurora—and in centers and
institutes across the state. Faculty and researchers are the foundation of the reputation for discovery and
innovation characteristic of the University of Colorado.
Both Campuses:
More than 135 degree programs in 13 schools and colleges (FY 2011-2012); collaborative degree
programs that prepare graduates to meet tomorrow’s challenges; over $400 million in sponsored research
awards, breaking ground in a number of areas, from advancing cancer treatments to creating more sustainable
urban infrastructures and better public schools; students educated on two campuses, online and in programs
and centers across the state of Colorado; less than 9 percent of total revenues are from state appropriations;
students come from 50 states and 67 countries; awarded 31% of all graduate degrees in the state, more than
any other Colorado institution (as of FY 2011-2012); more than 90 centers and institutes extending the reach
of teaching and research into the community, covering subjects from entrepreneurship and education policy to
medical and health concerns. The two campuses are connected by a shuttle service that runs hourly.
Denver Downtown Campus
The Department of Integrative Biology is located on the Denver downtown Campus, which is the main
undergraduate campus. Programs with convenient access to businesses, organizations, government offices
and cultural venues, yielding hands-on, relevant learning experiences through research and innovation,
internships and class projects; remarkable personal attention with student-faculty ratio of 17:1 one of
Colorado’s most diverse campuses–33 percent of Denver Campus undergraduate students are ethnic minority
and 32 percent are first-generation to college (fall 2011 end-of-term); student housing available adjacent to
campus; opportunity for undergraduates to conduct and receive funding for research projects.
Anschutz Medical Campus in Aurora
Anschutz is 40 minutes away by shuttle and houses many shared research resources. Highly selective
health sciences programs; an academic health sciences city for the 21st century; more than 6.5 million gross
square feet (projected upon campus completion) for cutting-edge research, education and clinical facilities;
adjacent to University of Colorado Hospital and Children’s Hospital Colorado, the University of Colorado
School of Medicine’s primary adult and pediatric hospital partners; borders industry partners at Colorado
Science + Technology Park at Fitzsimons; cares for more than 1 million patients a year.
PI Office
Faculty in the Department of Integrative Biology have individual offices that are an average of 120 sq ft that
are adjacent to their research labs.
PI Laboratory
Research Faculty in the Department of Integrative Biology have research laboratories that are an average
of 650 sq ft in a purpose built new Science building that opened in January 2010. The 4th floor of the Science
building houses the research labs of the Departments of Integrative Biology and Chemistry. Integrative Biology
research laboratories contain fume hoods, back up and dedicated power circuits, a sink with reverse osmosis
water supply, eyewash station and emergency shower. Dr. Charlesworth’s laboratory is set up to provide 4
bench work stations, two microscopy stations, a DNA purification station, a gel running station, a reagent
preparation station and a computer station. Research assistants also have desks in separate but nearby
Research Assistant Offices.
Computer
The Charlesworth laboratory contains a 27” iMac (2010) with backup hard drive, a PC that operates the
plate reader and a color printer that also copies and scans, all of which are for research use only. Dr.
Charlesworth’s office contains a MacBook Pro (2010) with a backup hard drive, a full sized keyboard and 24”
cinema display screen, and a color printer that also copies, scans and faxes. These office items are
multipurpose and are provided by the Department. Both Macs have Microsoft Office Suite for document
preparation, Adobe Creative Suite for data presentation, MacVector 11 for sequence alignment and analysis,
and EndNote X2 reference manager.
Animal Facilities
Xenopus laevis are housed in the basement of the Science building in a purpose built clean vivarium that is
maintained by professional veterinary staff from the Office of Laboratory Animal Resources and is accredited
by AAALAC. Users of the vivarium are required to wear clean disposable clothing (gown, cap, booties) into the
facility. Items to be brought into the facility are cleaned and sterilized by the professional staff before use. The
aquatics room is sealed with floor drains and a water supply. Xenopus are housed in a recirculating Xenopus
aquarium from Aquaneering with automatic temperature and pH control. New animals are kept in quarantine
before being added to the recirculating system. The facility is regularly inspected by the IACUC.
Common Departmental Laboratories
The Department has several shared laboratories: an autoclave room, a cold room, a wet ice maker, the
Molecular Core Facility, an Imaging Room (microscopy), a Dark Room (gel analysis) a plant growth room, a
temperature controlled research greenhouse automated by Wadsworth Control Systems and a growth
chamber room containing 3 Percival growth chambers. We also have close ties with the biochemists in
Department of Chemistry and we have access to their physical and analytical labs. We have already worked
with them for preliminary fluorescence anisotropy experiments to investigate RNA:protein interactions.
Common College Laboratories
The College of Liberal Arts and Sciences sponsors a University-wide Shared Analytical Services
Laboratory, available to faculty and students, that provides analytical services in support of research, e.g.,
HPLC, GC, LC MS, ICP, and AA. The Shared Analytical Services Laboratory is located in the Science building
on the same floor as the Department of Integrative Biology.
University of Colorado Denver Shared Resources
The Anschutz Medical Campus has several core facilities that are run on a fee for service basis. In this
proposal the following cores will be used:
CU Cancer Center DNA Sequencing & Analysis Service. Dr. Charlesworth is a member of the Cancer
Center and services in this core are discounted to center members through support by a NIH/NCI Cancer
Center Core Support Grant (P30 CA046934). We use this service for verifying mutations and plasmid integrity.
Protein Production, Monoclonal Antibody, Tissue Culture Shared Resource. We used this Resource for
protein expression in the baculovirus/Sf9 system (Charlesworth, 2012).
University of Colorado Denver Research Support
The Office of Research Development and Education arranges workshops on effective writing for both
manuscript submission as well as grant applications. The Center for Faculty Development provides
competitive $10,000 seed funds. The College of Liberal Arts and Sciences also provides competitive $10,000
CRISP (CLAS Research Innovation Seed Programs) awards and up to $2000 Dissemination grants through
the Associate Dean for Research and Creative Activities. The College of Liberal Arts and Sciences also has a
Capital Equipment Fund that provided funds for the LiCor Odyssey infrared scanner and a Zeiss LSM 700
confocal microscope. Grant administration is under the Office of Grant and Contracts in The Office of the Vice
Chancellor for Research, which also oversees institutional research compliance. The Office of Environmental
Health and Safety is responsible for hazardous waste disposal, biohazard, chemical and radiation. The Office
also assists in the safe running of research laboratories, including online safety training modules and monitors
laboratory safety compliance. For help with budgeting and expenses, the Department has a Business
Manager and at the college level the College Accountant, Financial Compliance Coordinator and an Assistant
Dean of Budget and Finance proactively help investigators stay on top of their budgets. Online training
modules are required for grant administration including budgeting, purchasing, travel and expense reports, as
well as training on safety and responsibility towards employees.
Institutional research support
The institution encourages research and therefore has a policy to arrange a differentiated workload
agreement to drop one course from my teaching load and switch that time and effort to research. To further
support the research programs of investigators the institution allows course buyouts to reduce teaching loads
and increase research time.
Intellectual Rapport
New faculty in the Department of Integrative Biology are actively mentored by a standing departmental
mentoring committee.
The Molecular and Cell Biology Supergroup brings together research labs from the Departments of
Integrative Biology, Chemistry and Psychology at the Denver Downtown Campus. This monthly meeting
includes Brad Stith (developmental and cell biology, lipid changes during meiosis and fertilization in Xenopus
laevis), Aaron Johnson (RNA splicing and gene expression in Drosophila development), Christopher Phiel
(DNA methylation, wnt signaling), Raibatak Das (receptor internalization and mobility on membranes),
Jefferson Knight (mechanisms of molecular interaction that underlie the biological process of insulin secretion.
Dr. Knight has already collaborated with us for biochemical Kd calculations on our latest publication), Hai Lin
(development of new methodology for computer modeling and simulations of complex systems in chemistry,
biochemistry and biophysics), Scott Reed (nanoparticle-lipid conjugates as membrane mimics, nanomaterials
for phototherapeutic applications), Xiaojun Ren (Molecular Biophysics, Stem Cells and Epigenetics), Marino
Resendiz (RNA aptamers) and Richard Allen (Psychopharmacology). Drs. Stith, Johnson and Charlesworth
form a Developmental Biology focus in the Department.
There is a monthly RNA Club for faculty, students and post-docs at the Anschutz Medical Campus that Dr.
Charlesworth and lab members regularly attend. Other PI members are Richard Davis (Novel forms of RNA,
RNA metabolism, and chromatin diminution), Tom Evans (Molecular and cellular mechanisms of early
embryonic development in C. elegans, letter of support included), Jay Hesselberth (Genomics of gene
regulation), Jeffrey Kieft (Protein Translation and RNA structure and a Howard Hughes Investigator), and Rui
Zhao (Molecular mechanism of pre-mRNA splicing).
Student Population
The University of Colorado Denver provides a diverse body of students with opportunities to enhance their
lives, careers and research. Today, the university offers more than 130 programs in 13 schools and colleges at
the undergraduate, graduate, doctoral and professional health levels. Our students are from 50 states and
more than 130 countries.
Educating more than 14,000 students on our comprehensive campus in downtown Denver and more than
3,000 students in our research and advanced health care programs at the Anschutz Medical Campus, the
University of Colorado Denver is one of the nation’s top public urban research universities.
The Department of Integrative Biology currently has about 1200 declared Biology majors and a further
1000 pre-health majors. The high quality of our Integrative Biology Department is proven by the finding that a
large number of Biology undergraduates go on to graduate or professional programs. We have one of the
highest acceptance rates at the School of Medicine, University of Colorado Anschutz Medical Center,
compared to any other branch, university or college in the state of Colorado. Dr. Ferguson (our preprofessional advisor) estimates that, over the past 15 years, some 700 students have obtained a bachelor
degree in biology and went on to a doctorate (we average about 35 students per year entering Medical School
alone).
Biology Master of Science
The Department of Integrative Biology Master of Science program offers students the opportunity to
receive advanced training and research experience in an area of specialization of one of our nationally and
internationally recognized faculty members. The MS program in biology is designed to prepare graduates for
careers in research and teaching; for employment in business, industry and government; for existing career
advancement; and for continuing post-baccalaureate work in PhD and professional programs. Alumni of the
biology MS program have gone on to careers in medicine, research, teaching, and policy and regulation,
among others. As part of the biology MS program, Graduate Teaching Assistantships are available.
PhD in Integrative and Systems Biology Program
The Ph.D. Program in Integrative and Systems Biology at the University of Colorado Denver is a
multidisciplinary, dual campus (Denver Downtown Campus and Anschutz Medical School) program that offers
students opportunities to address complex questions in biology using computational, laboratory, and field
approaches. The more than 40 program faculty members allow students to participate on a diversity of
projects at all levels of biological organization, ranging from ecology and environmental microbiology to
biochemistry, developmental biology, and neuroscience. Depending on the track an incoming student chooses,
the approach will either be to explore the problem at multiple levels of biological organization (Integrative
Biology) or to explore the multi-component nature of a biological system (Systems Biology). Students are
supported by the Graduate School in their first year. PhD students in the laboratory of Dr. Charlesworth will
focus on the integrative nature of biology, by exploring the evolutionary conservation of protein structure of Zar
binding to RNA, all the way through the role of Zar in embryogenesis.
Student Research Support Programs
The University strongly supports training undergraduate and graduate students in research. To promote
these goals, several programs are available.
The Undergraduate Research Opportunities Program (UROP) enhances undergraduate education by
funding students engaged in research, scholarly, creative, and entrepreneurial activities in collaboration with
faculty at the Downtown Campus of the University of Colorado Denver. The BRAiN program aims to raise
interest and opportunities in neuroscience research for individuals who are typically underrepresented in the
field through enhancing Neuroscience Diversity through Undergraduate Research Education Experiences,
R25GM097633. Biology Research Scholars are encouraged to pursue research as part of their undergraduate
education. Students who excel in both course work and research will be recognized as Biology Research
Scholars. Work study is administered by the financial aid office and is based on financial need. Typically,
students can earn up to $3200 per semester from the Financial Aid Office, which pays for 75% of the student’s
hourly rate and the employer pays the remaining 25% of the hourly rate. For undergraduates interested in
research, work study allows students to spend time in the laboratory rather than having to work another job to
pay for their tuition.
The Independent study program study is a for credit program that is available to undergraduate and
graduate students and is administered at the discretion of the faculty advisor. Students can earn up to 6
credits of independent study for graduation. Typically students perform research projects and write up these
projects in a final paper. Dr Charlesworth’s requirements are a demonstrated competence in General Cell
Biology and General Genetics and a 2 semester minimum commitment to laboratory research.
The Graduate School is also highly supportive of graduate, MS and PhD, students by offering tuition
remission on an as-needed basis, by fully supporting PhD students in their first year of training, and by offering
several graduate student oriented workshops throughout the academic year.
Student Research Success
In the first three years at UCD, Dr. Charlesworth has mentored one non-thesis Master’s student and three
undergraduate students in lab research that yielded high quality, publishable, data. Kevin Silva
(undergraduate) was a UROP awardee and a Biology Research Scholar. Kevin has graduated and is applying
to medical schools with research opportunities. Kevin made mutant Zar2 proteins and contributed EMSA
studies and subcellular localization studies to two manuscripts. Cassandra Kotter (non-thesis Masters’
student) has graduated and is a now a Professional Research Assistant at the Anschutz Medical Campus.
Cassandra contributed to two manuscripts with sequence alignment data and EMSA studies, and made
Zar2mt12. Terry Khat (undergraduate) was a UROP awardee. Terry made the mutant Zar1 proteins and
contributed EMSA studies to the Zar1 manuscript. Kevin and Terry are now members of the American Society
for Cell Biology and they presented a poster on their research at the 2011 Annual Meeting. Michael Ferreyros
(undergraduate) is part of the BRAiN program and contributed EMSA studies to the Zar1 manuscript.
Jonathan Cook became a master’s student in Fall 2012 and presented his work in poster format at Cold Spring
Harbor Laboratory Translational Control 2012 meeting.
Denver Metro Area Biomedical Scientist Population
There is a plentiful supply of cell and molecular biology specialized PhDs in the Denver metro and
surrounding areas that come from PhD programs at the University of Colorado Denver Anschutz Medical
Campus (Biochemistry and Molecular Genetics; Cancer Biology; Cell Biology, Stem Cells and Development;
Computational Bioscience; Integrative and Systems Biology; Molecular Biology; Physiology and Biophysics;
Reproductive Sciences; Structural Biology and Biophysics); University of Colorado Boulder (Molecular, Cellular
and Developmental Biology; Chemistry and Biochemistry); Colorado State University (Biochemistry; Cell and
Molecular Biology), University of Denver (Biological Sciences; Molecular and Cellular Biophysics). Tomomi
Yamamoto was an experienced post-doctoral research associate from the Anschutz Medical Campus and
contributed to both our recent Zar publications.
Equipment
PI Laboratory
Eppendorf 5415D microcentrifuge; Beckman 22R refrigerated microcentrifuge; Thermo Scientific MaxQ
4000 shaking incubator; heat blocks, heater/stirrers; vacuum pump for plasmid prep manifold; microwave;
Orbitron Rotator I; Symphony pH meter; Sartorius TE3102S balance and TE64 analytical balance; selection of
incubators for 18°C, 24°C, 30°C and 37°C; 2x Leica M8o dissecting scope; Leica IC80 HD digital camera with
Samsung HD monitor; Drummond Nanoject II microinjector and micromanipulator; MJ Research PTC-200
thermocycler; BioRad C1000 Thermocycler with gradient block; BioTek Synergy HT plate reader with UV/vis
absorbance, fluorescence and luminescent capability, with dual injectors for luciferase assays; BioRad
powerpacs, 300, HC and basic; E-C Apparatus EC250-90 powerpack; UVP benchtop transilluminator; Reliable
Scientific platform rocker; assorted nucleic acid gel boxes; assorted protein gel boxes and transfer cells; vortex
mixers; picofuges; -20 alarmed enzyme freezer; -20 upright freezer; 4 upright refrigerator; Leica RM2135
microtome; Lab-Line slide warmer. In the neighboring Dr. Stith’s lab we use the WPI Pul-1 glass needle puller;
Virtis Virsonic 50 sonicator.
Common Departmental Laboratories
Equipment crucial to this project in bold. The Molecular Core Facility has 3x Eppendorf Pro S
Mastercyclers; 3x -80°C freezers; -20°C freezer; 4°C refrigerator; Fotodyne digital camera, UV light box, PC
and FOTO/Analyst® PC Image for nucleic acid gel analysis; Thermo Scientific Nanodrop 3300; Thermo
Sorvall Legend X1R refrigerated benchtop centrifuge; Beckman GP benchtop centrifuge, Turner SP830
spectrophotometer; BioRad Gel Dryer 543; Nuaire biological safety cabinet; Lab Companion SI-300 benchtop
shaking incubator; Thermo Sorvall WX Ultra 80 ultracentrifuge; Damon/IEC B-20A preparative centrifuge;
BioRad iQ5 multicolor real time PCR; incubator; Spectrolinker XL-1500 UV Crosslinker; Savant DNA 120
SpeedVac; fume hood; Advantage A10 Millipore MilliQ water purifier.
The Imaging Room has Olympus inverted light microscope, Olympus BH2 upright light microscope, Nikon
fluorescent microscope and Zeiss LSM 700 confocal microscope.
The Dark Room contains Perkin Elmer Cyclone Storage Phosphor System; LKB 1209 Rackbeta liquid
scintillation counter; LiCor Odyssey infrared gel scanner; LiCor 4300 DNA Analyzer. The Department also
has a BD Accuri C6 Flow Cytometer.
The chemistry labs have PTI QuantaMaster fluorescence spectrometer capable of emission, excitation,
lifetime, and polarization / anisotropy experiments; Perkin Elmer LS-55 steady state fluorescence spectrometer
instrument capable of anisotropy measurements; Rainin dual pump gradient HPLC with computer-based
gradient controller with UV and evaporative light scattering detector; Perkin Elmer Lambda 35 and Lambda 650
spectrophotometers equipped with excitation and emission monochromators that can be scanned over the
UV/visible spectral range from 200-800nm; GE Akta Purifier UPC10 FPLC system with Hg lamp and filters for
detection at 254, 280, and 546 nm; Zetasizer Nano-S90 for the size and molecular weight measurement of
dispersed particles (Size range (d): 0.3nm - 5 mm) at a 90° scattering angle. Includes 4mW 633nm He-Ne
laser.
Common College Laboratories
The Shared Analytical Services Laboratory contains 4000 QTRAP hybrid triple quadrupole-linear ion trap
mass spectrometer; 3 HPLCs, gas chromatographs, scintillation counters; inductively coupled plasma
spectrometer; 3 atomic absorbance spectrometers; ion chromatograph; UV-Vis and FTIR spectrophotometers.
The Colorado Advanced Photonics Technology (CAPT) Center is located on the downtown campus of
UCD. The Optical Characterization and Metrology Lab at CAPT contains the following major equipment:
Digital Instruments Atomic Force Microscope (AFM); Wyko NT2000 Non Contact Surface Profiler; Dektak
200VSi Stylus Profilometer; Cary 500 Spectrophotometer; Wyko 6000 Interferometer; Nikon Measuring
Microscope System; Optikos Video MTF Measurement System; Sopra GESP5 Spectroscopic Ellipsometer
University of Colorado Denver Shared Resources (at the Anschutz Medical Campus, hourly shuttle
service available)
Sequencing Core has several ABI 3730 capillary DNA sequencing instruments.
Proteomics Core has ThermoFisher LTQ FT Ultra linear ion-trap Fourier transform ion cyclotron resonance
mass spectrometer; GE Healthcare Multi Dimensional Liquid Chromatography (MDLC) system; Perseptive
Biosystems Voyager STR+ MALDI-TOF mass spectrometer; PE Biosystems Voyager STR+ MALDI-TOF mass
spectrometer; Applied Biosystems Q-STAR XL mass spectrometer; and a ThermoFisher LTQ Orbitrap linear
ion-trap Fourier transform ion cyclotron resonance mass spectrometer coming soon.
Bioinformatics Shared Resource include a departmental cluster that consists of 12 Dell PowerEdge M610
blades with 12 2.8Ghz dual-core processors and 96 GB memory each for the analysis of NextGen highthroughput sequencing. In addition, the cluster has one high-memory node (Dell PowerEdge R810 with 16
2.27Ghz dual-core processors and 512GB of memory) that is dedicated to the analysis and assembly of
NextGen sequencing data. Storage capacity of the cluster is 109TB provided by six Dell PowerVault MD1200
disk arrays. These disk arrays are managed by two Dell PowerEdge R710 servers with 10GbE connectivity to
the blade enclosure and tape backup system. The cluster is managed through the Platform HPC software
suite running on an additional Dell PowerEdge R710 server. Should larger computational needs arise; we have
access on a fee-for-service basis to the Janus cluster located at the University of Colorado Boulder, which
consists of 16,416 CPUs and nearing 1 PB of online storage.
The campus also has a microarray and genomics core, that houses one Illumina HiSeq 2000, one HiSeq
2500, and one Ion Torrent. The libraries made in-house or extracted RNA/DNA can be sent to the Genomics
Core for processing and sequencing.