Cell Biology: Concepts, Approaches and Translational Impact
Proposed Syllabus, Spring 2017
COURSE INFO:
Course Organizer: Dr. Pam Cowin <[email protected]>
COURSE GOALS:
Modern cell biology is an exciting discipline relevant to all biologists. In addition, cell biological
techniques are essential for mechanistic analysis and preclinical drug validation and hence the study of
cell biology is also relevant to the fields of translational and regenerative medicine and drug discovery.
Cell biology has played a critical role in the discovery of adult tissue stem cells and reprogramming.
Cell biology covers a broad spectrum ranging from subcellular analysis of organelles, cytoskeletal
complexes and protein trafficking to studies of complex cell interactions and behaviors. Thus cell
biology intersects with and complements the fields of developmental biology, illuminating mechanisms
essential for the formation and maintenance of tissues. It has provided critical insight into understanding
the inappropriate proliferative states and metastatic behavior of tumor cells in cancer biology and the
disintegration of tissues in degenerative pathologies. This course aims to stimulate exploration of
concepts and current approaches in modern cell biology and offers a range of active learning and
participatory modules to achieve this.
COURSE DESCRIPTION:
The course will cover a broad range of topics relevant to cell biology. It emphasizes basic fundamental
cell biology and highlights translational medical applications. The course will cover the following
concepts and themes: cell and molecular interactions governing potency, differentiation and plasticity
among cellular hierarchies, mechanisms of cell adhesion, migration, communication and dynamic
cytoskeletal reorganization in the construction of tissues, regulation of cell proliferation and cell death,
and subcellular protein trafficking and signaling. The aberration of these processes in relevant
pathological situations will also be discussed throughout the course. The lecture/tutorial format will give
students a broad background and the opportunity to engage in discussion on exciting recent data in the
field.
COURSE LOGISTICS:
3 credits.
Two 90-minute lectures/week in SK3 9-10:30am Tuesdays and Thursdays.
One 90-minute small group tutorials on Friday morning. Each group explores a different paper along a
common theme and this is to stimulate a greater breadth of knowledge as a whole by stimulating “after
class” discussion among the student body. There will be one week when in place of the above format
students will be divided into 3 research groups and given free rein to explore present a 30 minute ppt on
a chosen topic to the class.
GRADING:
In this course we focus on achieving education through preparation and active participation by the
students. They are expected to come to class having read set current reviews prior to each of the two
weekly lectures. They are encouraged to bring questions and actively engage with the lecturer in order
to reach a conceptual understanding of the topic. Small group tutorials are an important aspect of this
course where students meet with different faculty in groups of three or four to discuss the concepts
raised by a current paper within a tutorial setting. Students sign up for tutorial group assignments at the
beginning of the course so that they can build this in depth aspect of the curriculum in accord with their
own particular research interests.
There will be a take home essay at the end of the course. Students are allowed to choose from a sign up
list of topics and are also encouraged to suggest a topic to explore in this manner to a faculty lecturer in
the course.
Grading is de-emphasized The goal is that all students will work actively throughout the course to
acquire their own education rather than be tested. This is emphasized at the opening of the course.
Grades are based on preparation for class as judged by their active participation in lectures, ppt
presentations and tutorial discussion, as well as on their take home essay. Lecturers will be asked to
provide feedback on the essay and students may seek guidance while writing it so that the “exam”
becomes an education in itself.
Relevant programs: Stem Cell Biology, Cellular and Molecular Biology, Developmental Genetics,
Molecular Oncology and Immunology, Molecular Pharmacology, Pathobiology, Biomedical imaging
and informatics
Week 1: Stem Cells, Lineage and Plasticity
Goal: To introduce students to the concepts and mechanisms by which cell diversity is generated, maintained
and/or reprogrammed. The first lecture uses intestine to discuss concepts of the stem cell hierarchy and the niche
in generating reserved quiescent as well as activated zones of stem cell activity. It discusses how the stem cells
generate the niche and are regulated by the niche. It introduces the role of Wnt Hh and Notch signaling in these
processes. Colon cancer is discussed as an example of how deregulated stem cell activity predisposes to cancer
and is presented as a careful parsing of the distinction between stem and cancer stem cells. The second lecture
covers the development of ES cells from prior work on teratomas emphasizing the concepts of niche and potency.
Through learning about iPS cells students gain insight into the control of potency and differentiation and the
plasticity of the cellular state. Tutorials: Recent primary literature will be selected to build upon themes of iPS
manipulation, lineage tracing, in vitro models of stem cell and cancer stem cell activity.
Day
Date
Room
Lecturer info
Topic
Time
Tues Jan. 10 SK-3
Dr. Pam Cowin.
[email protected]
x38715 MSB 621
Adult Tissue Stem Cells
9:00-10:30am
Thurs Jan. 12 SK-3
Dr. Matthias Stadtfeld
ES and IPS Cells
[email protected]
(646) 501-6750 SK4 lab 1
Fri
TUTORIALS
Jan. 13
MSB659
MSB424
MSB659
Pam Cowin
[email protected]
Markus Schober [email protected]
Mayumi Ito [email protected]
9:00-10:30am
9:00- 10:30 am
10:30-12:00am
10:30-12:00am
Last year’s readings
lectures:
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 22, pp 1251-1262
Cell. 2008 Feb 22;132(4):567-82. doi: 10.1016/j.cell.2008.01.015.
Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Jaenisch R1, Young R.
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 22, pp 1217-1227
Cell. 2013 Jul 18;154(2):274-84. doi: 10.1016/j.cell.2013.07.004.
The intestinal crypt, a prototype stem cell compartment. Clevers H1.
Tutorial Papers:
Nature. 2015 Jan 1;517(7532):81-4. Identification of multipotent mammary stem cells by protein C receptor
expression.Wang D1, Cai C1, Dong X1, Yu QC1, Zhang XO2, Yang L2, Zeng YA1.
Nature. 2012 Sep 13;489(7415):257-62. Distinct contribution of stem and progenitor cells to epidermal
maintenance. Mascré G1, Dekoninck S, Drogat B, Youssef KK, Broheé S, Sotiropoulou PA, Simons BD,
Blanpain C.
Cell. 2006 Aug 25;126(4):663-76. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast
cultures by defined factors. Takahashi K1, Yamanaka S.
Week 2: Extracellular Matrix, Cell-Matrix Mechanotransduction via Integrinmediated signaling and stretch activation of TGF-beta.
The first lecture will cover the large integrin family and the diverse roles of its members in cell-matrix, cell-cell
and clotting interactions. Signaling from kinases and adaptors localized at focal contacts will be covered and the
mechanisms of inside out and outside in signaling at these sites. Structural changes in integrin shape and
clustering that lead to activation will be discussed. The recently emerging role of specific integrins as mechanotransducers essential for stretch-mediated TGF-beta activation and the consequence of this for cell motility, EMT
and feedback loop to matrix synthesis will be introduced. The second lecture will briefly review matrix
composition and the role of fibroblasts in its synthesis and then build upon the first lecture through the paradigm
of Marfan syndrome, which was initially viewed as a genetic disease in which mutations compromised elastic
fibers. More recent work has shown that the elastic fiber defect produces results in loss of docking sites for latent
TGF-beta and BMP and when compromised results in excessive signaling due to failure to sequester and locally
activate these signaling molecules. This illustrates the interconnection and feedback between the matrix
surroundings of cells and signaling that affects their motility and matrix production with pathological
ramifications for multiple genetic syndromes as well as EMT induction in cancer and distortion of niche-induced
stem cell quiescence in other settings.
Day Date
Room
Lecturer info
Topic
Time
Tues Jan. 17 SK-3
John Munger
Integrins as mechanosensors
Thurs Jan. 19 SK-3
Dan Rifkin
[email protected]
x 35109 MSB 638
Extracellular Matrix
TGFb/BMP signalosome
Fri
TUTORIALS
Matthias Kugler
Matthias Kugler
Dan Rifkin. [email protected]
Dan Rifkin. [email protected]
Jan. 20
MSB659
MSB659
MSB424
MSB424
9:00-10:30am
9:00-10:30am
10:30-12:00am
9:00-10:30am
10:30-12:00am
Last year’s readings
Lectures:
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 19, pp 1057-1080
FEBS Lett. 2012 Jul 4;586(14):2003-15. doi: 10.1016/j.febslet.2012.05.027. Epub 2012 May 26.
Matrix-dependent perturbation of TGFβ signaling and disease.
Doyle JJ1, Gerber EE, Dietz HC.
Tutorials
J Clin Invest. 2014 Jan;124(1):448-60. doi: 10.1172/JCI69666. Epub 2013 Dec 20.
Angiotensin II-dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis.
Gallo EM, Loch DC, Habashi JP, Calderon JF, Chen Y, Bedja D, van Erp C, Gerber EE, Parker SJ, Sauls K,
Judge DP, Cooke SK, Lindsay ME, Rouf R, Myers L, ap Rhys CM, Kent KC, Norris RA, Huso DL, Dietz HC.
J Clin Invest. 2014 Mar;124(3):1329-39. doi: 10.1172/JCI71059. Epub 2014 Feb 17.
Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome.
Cook JR, Carta L, Bénard L, Chemaly ER, Chiu E, Rao SK, Hampton TG, Yurchenco P; GenTAC Registry
Consortium, Costa KD, Hajjar RJ, Ramirez F.
Week 3: Adhesion, Polarity and Migration
The first lecture emphasizes the role of cell-cell interactions and behaviors in building tissues. The first lecture
will contrast fibroblastic and epithelial social behavior, review the history of experimentation and thought in cell
adhesion form reconstituting sponges to interfering with slime mold aggregation and the contribution of these
model organism studies to the elucidation of the major molecular adhesive mechanisms. We will discuss the
physical molecular and structural basis of cell adhesion with emphasis on dynamic transitory (immunological
synapse) and the relative roles of adherens junctions in initiating epithelial cell adhesion and desmosomes in
reinforcing and stabilizing epithelial associations. The role of the cytoskeleton in regulating cadherin based
adhesion in stem cell niche and its loss, switching and deregulation in EMT and cancers will be covered and its
modulation in morphogenesis such as during convergent extension. The role of beta-catenin as a modulatable link
in cell adhesion and a central signal-transducer-transcriptional factor in Wnt signaling will be reemphasized as
will the role of p120 catenin and kaiso as example of dual feedback regulators of adhesion and transcription. The
second lecture concentrates on cell migration and the role of the GTPases Rho Rac and Cdc42 in lamellipodia,
filopodia and cytoskeletal dynamics. Contact guidance, directed individual and collective cell migrations and
response to gradients will be covered.
Tues Jan 24
SK-3
TBA
Dr. Pam Cowin
[email protected]
x38715 MSB 621
OR
Dr. Jeremy Nance
[email protected]
x33156 SK4 lab 17
Thurs Jan 26
SK-3
Fri Jan. 27
MSB 424
MSB659
MSB424
MSB659
TUTORIALS
Holger Knaut. [email protected]
Pam Cowin [email protected]
Holger Knaut. [email protected]
Pam Cowin [email protected]
Cell-Cell Adhesion
9:00am-10:30
Asymmetry and Polarity
9:00-10:30
Holger Knaut Collective Migration EMT &
[email protected] Motility
x37227 SK4-15
9:00-10:30am
9:00-10:30am
9:00-10:30am
10:30-12:00am
10:30-12:00am
Last year’s readings
Lectures
Alberts et. al., Mol. Biol of the Cell, 6th edition. Chapter 16, pp 951-962 & Chapter 21, pp 1184-1197
Development. 2014 May;141(10):1999-2013. Cell migration: from tissue culture to embryos. Reig G1, Pulgar E,
Concha ML.
Nat Rev Mol Cell Biol. 2014 Jun;15(6):397-410. Dynamic contacts: rearranging adherens junctions to drive
epithelial remodelling. Takeichi M1.
Tutorials
Dev Cell. 2006 May;10(5):673-80. Chemokine signaling mediates self-organizing tissue migration in the
zebrafish lateral line. Haas P1, Gilmour D.
Dev Cell. 2014 Oct 27;31(2):171-87. A molecular switch for the orientation of epithelial cell polarization.
Bryant DM1, Roignot J1, Datta A1, Overeem AW1, Kim M1, Yu W1, Peng X1, Eastburn DJ1, Ewald AJ1, Werb
Z1, Mostov KE2.
Week 4: Concepts In Subcellular Membrane Trafficking
Day
Room
Lecturer info
Tues Jan 31
SK-3
Dr. Don Ryoo
ER, protein
[email protected] translocation
x37257 MSB493
folding, processing &
trafficking to Golgi
Thurs Feb. 2
SK-3
Dr. Niels Ringstad
[email protected]
x33753 SK5-14
Fri
Date
Feb. 3
MSB659
MSB659
MSB 424
MSB 424
Topic
Time
9:00-10:30am
Endocytosis, Phagocytosis 9:00-10:30am
TUTORIALS
Dr. Don Ryoo [email protected]
Dr. Don Ryoo [email protected]
Dr. Niels Ringstad [email protected]
Dr. Niels Ringstad [email protected]
9:00-10:30am
10:30-12:00 am
9:00-10:30 am
10:30-12:00 am
------------------------------------------------------------------------------------------------------------
Last years readings
F1000Prime Rep. 2014 Jul 8;6:49. doi: 10.12703/P6-49. eCollection 2014.
Protein quality control in the endoplasmic reticulum.
Koenig PA1, Ploegh HL2.
Annu Rev Biochem. 2009;78:857-902. doi: 10.1146/annurev.biochem.78.081307.110540.
Mechanisms of endocytosis.
Doherty GJ1, McMahon HT.
Cold Spring Harb Perspect Biol. 2013 Dec 1;5(12):a016949. doi: 10.1101/cshperspect.a016949.
Endocytosis and cancer.
Mellman I1, Yarden Y.
Tutorials
Cell. 2014 Sep 11;158(6):1375-88. doi: 10.1016/j.cell.2014.07.050.
Key steps in ERAD of luminal ER proteins reconstituted with purified components.
Stein A1, Ruggiano A2, Carvalho P2, Rapoport TA3.
A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human
fibroblasts.Anderson RG, Goldstein JL, Brown MS. Nature. 1977 Dec 22-29;270(5639):695-9.
Cell. 1976 Dec;9(4 PT 2):663-74.Analysis of a mutant strain of human fibroblasts with a defect in the
internalization of receptor-bound low density lipoprotein. Brown MS, Goldstein JL.
Week 5:
Cell Death, Cell Division and Protein Degradation
The first lecture covers apoptosis, necrosis and programmed cell death and the role of
the mitochondria and caspase signaling in these processes. The second lecture
focuses on the roles of cyclins, cdks, phosphatases, protein degradation via F-box
proteins and ubiquitination as mechanisms controlling the unidirectional cycle of cell
division.
Tues Feb 7
SK-3
Dr. Don Ryoo
Cell Death mechanisms
[email protected]
x37257 MSB493
9:00-10:30am
Thurs Feb. 9
SK-3
Dr. Michele Pagano
[email protected]
SM1103 x35332
9:00-10:30am
Fri
Feb. 10
MSB 424
MSB 424
MSB659
MSB659
Cell Cycle &
Protein degradation
TUTORIALS
Julia Pagan
Julia Pagan
Don Ryoo. [email protected]
Don Ryoo. [email protected]
9:00-10:30 am
10:30-12:00 am
9:00 - 10:30am
10:30-12:00am
Last year’s readings
Lectures:
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 17, pp 963-1020
Mechanisms and function of substrate recruitment by F-box proteins.
Skaar JR, Pagan JK, Pagano M. Nat Rev Mol Cell Biol. 2013 Jun;14(6):369-81.
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 18, pp 1021-1032
Immunity. 2011 Oct 28;35(4):441-4. The end and after: how dying cells impact the living organism. Green DR1.
Tutorials
Nat Cell Biol. 2011 Dec 4;14(1):51-60. Autophagic targeting of Src promotes cancer cell survival following
reduced FAK signalling. Sandilands E1, Serrels B, McEwan DG, Morton JP, Macagno JP, McLeod K, Stevens C,
Brunton VG, Langdon WY, Vidal M, Sansom OJ, Dikic I, Wilkinson S, Frame MC.
Mol Cell. 2014 Apr 10;54(1):133-46. Epub 2014 Apr 3.
Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by
RIP3. Wang H1, Sun L1, Su L2, Rizo J2, Liu L1, Wang LF3, Wang FS3, Wang X4.
Week 6: Microtubule and Actin filament Dynamics
Microtubule dynamic assembly, behavior, enzymatic function and isolation and role in trafficking and vesicular
transport, flagellar, cilia and signaling. Actin filament structure as revealed by crystallography and EM and
biochemical analyses, assembly characteristics, treadmilling, interactions with myosin, regulation by bundling,
severing and capping proteins, cellular functions in cortical and filamentous cytoskeleton, role at adherens and
focal contact cell junctions, axons, dendrites and in contractile rings during cell division.
Tues Feb. 14 SK-3
Dr. Nick Cowan
Microtubule
[email protected] Dynamics
x38166 MSB315
9:00-10:30am
Thurs Feb. 16 SK-3
Ed Ziff
[email protected]
x35774 SK5-1
9:00-10:30am
Fri
TUTORIALS
Ed Ziff
Ed Ziff
Nick Cowan. [email protected]
Nick Cowan. [email protected]
Feb. 17
MSB659
MSB 659
MSB424
MSB424
Actin Dynamics
9:00-10:30am
10:30-12:00am
9:00-10:30am
10:30-12:00am
Last year’s readings
Lectures:
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 16, pp 925-943
J Cell Sci. 2010 Oct 15;123(Pt 20):3415-9. Microtubule +TIPs at a glance.
Akhmanova A1, Steinmetz MO.
Alberts et. al., Molecular Biology of the Cell, 6th edition Chapter 16, pp 889-965
Science 326, 1208 (2009); Actin, a Central Player in Cell Shape and Movement Thomas D. Pollard and John A.
Cooper
Tutorials
Cell. 2012 Apr 13;149(2):371-82. EBs recognize a nucleotide-dependent structural cap at growing microtubule
ends. Maurer SP1, Fourniol FJ, Bohner G, Moores CA, Surrey T.
Nat Med. 2009 Sep;15(9):1055-61. doi: 10.1038/nm.2011. Epub 2009 Aug 23.
PMID: 19701205. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis.
Wong SY, Seol AD, So PL, Ermilov AN, Bichakjian CK, Epstein EH Jr, Dlugosz AA, Reiter JF.
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):E1361-70. Integrin-dependent force transmission to the
extracellular matrix by α-actinin triggers adhesion maturation. Roca-Cusachs P1, del Rio A, Puklin-Faucher E,
Gauthier NC, Biais N, Sheetz MP.
Week 7: Motor Proteins and Student Presentations
The structural, cell biological and signaling roles of dyneins, kinesins and myosins.
Tues Feb. 21 SK-3
Dr. Gira Babha
[email protected]
SK2.
Motor Proteins
9:00-10:30am
Thurs Feb. 24 SK-3
Student Presentations on selected topics
9:00-10:30am
Fri
Student Presentations on selected topics
Pam Cowin
9:00-12:00am
Feb. 17
MSB659
Last year’s readings:
How Dynein Moves Along Microtubules.Bhabha G, Johnson GT, Schroeder CM, Vale RD.
Trends Biochem Sci. 2016 Jan;41(1):94-105. doi: 10.1016/j.tibs.2015.11.004. Review.
Allosteric communication in the dynein motor domain.Bhabha G, Cheng HC, Zhang N, Moeller A, Liao M, Speir
JA, Cheng Y, Vale RD. Cell. 2014 Nov 6;159(4):857-68. doi: 10.1016/j.cell.2014.10.018.