Lahore University of Management Sciences

Cell Signaling (BIO 611)

Fall 2015

Instructors Amir Faisal

Room No. TBA
Office Hours TBA
Email Amir.faisal@lums.edu.pk
Telephone 8453
Secretary/TA Iqra Manzoor / Aishah Bilal
TA Office Hours NA
Course URL (if
any)

Course Basics
Credit Hours Three (3)
Lecture(s) Nbr of Lec(s) Per Two (2) Duration 50 minutes
Week
Recitation/Lab (per week) Nbr of Lec(s) Per One (1) Duration 50 minutes
Week
Tutorial (per week) Nbr of Lec(s) Per none Duration
Week

Course Distribution
Core Yes (for graduate students)
Elective Yes (for undergraduates)
Open for Student Biology majors and minors
Category
Close for Student Others
Category

COURSE DESCRIPTION
Cells in multicellular organism communicate with each other and internally by a complex network of signaling pathways
that regulate cellular processes such as growth, differentiation, migration, survival and apoptosis. This course aims to
provide comprehensive understanding of different signaling components and pathways involved in such processes and
how deregulation of key signaling proteins involved in these pathways leads to human diseases such as cancer. There
will be two lectures every week followed by a session of recitations where students will discuss a paper relevant to the
topic studied during the week. Assignment at the end of the course will consist of research paper of choice to be
presented to the class.

COURSE PREREQUISITE(S)
Students enrolled in this course are expected to have taken at least introductory level courses in molecular biology,
cell biology or biochemistry
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COURSE OBJECTIVES
The course aims to help student learn the following:

The general principles of cell signaling

Signaling molecules and their receptors
Transmission of signals within the cell (Signaling pathways and networks)
How signaling is subverted in cancer cells
Therapeutic strategies targeted at cell signaling

Learning Outcomes
After taking this course students should:

Be able to appreciate and understand the basic principles of cell signaling

Have a good understanding of key signaling pathways
Know how deregulation of signaling proteins (and pathways) leads to cancer
Understand the modern methods of targeted cancer therapeutics

Grading Breakup and Policy

Assignment: 10%
Midterm Examination: 35%
Quiz: 15%
Recitations: 5%
Final Examination: 35%

Examination Detail

Yes/No: Yes
Combine/Separate: Combined
Midterm
Duration: 3 hours
Exam
Preferred Date: None
Exam Specifications: Short answer questions

Yes/No: Yes
Combine/Separate: Combined
Final Exam
Duration: 3 hours
Exam Specifications: Short answer questions
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COURSE OVERVIEW
Recommended
Weeks Topics Tutorial paper
Readings
Introduction to the course Book A: 879-889 Starkey R et al. Epidermal Growth
General principles of cell signaling Book B: 115-133 Factor: Identification of a New
Components of cell signaling Hormone in Human Urine.
Ligands and receptors Science 189 1975
Week 1
(Demonstrates how human
Epidermal Growth Factor (EGF)
was isolated)

Nuclear receptors Book A: 904-921 Switching of the coupling of the

G protein coupled receptors (GPCRs) Book B: 151-175 and 179-225 beta2-adrenergic receptor to
different G proteins by protein
Week 2
kinase A Daaka et al Nature 390
1997

Second messengers Book A: 908-915 and 922-928 Epidermal growth factor induces
Receptor tyrosine Kinases (RTKs) Book B: 231-264 and 311-326 rapid tyrosine phosphorylation of
proteins in A431 human tumor
Week 3 cells. Hunter T et al Cell 1981
(One of the first papers to
propose mechanism of action of
EGF in intact cells)
Signal Transduction Book A: 897-904 Src homology region 2 domains
Protein modifications Book B: 328-351 and 269-305 direct protein-protein interactions
Protein phosphorylation: Kinases and in signal transduction. Moran MF
phosphatases et al PNAS 87(21) 1990
Week 4 Spatial and temporal aspects of (Regulation of protein-protein
signaling interactions by reversible protein
phosphorylation and specific
domains that recognize phospho-
tyrosine residues)
Signaling pathways Book A: 926-931 c-Jun NH(2)-terminal kinase is
MAP Kinase pathways Book B: 383-391 and 355-375 essential for the regulation of AP-
Ras proteins 1 by tumor necrosis factor.
Week 5 Ventura JJ et al MCB 23(8) 2003.
(Shows how transcription factors
are regulated by cytokines via a
MAPK pathway)
Lipid signaling and PI3 Kinase Book A: 932-935 Mitogenic Activation,
Akt/PKB and mTOR signaling PI3K signalling: the path to Phosphorylation, and Nuclear
discovery and understanding. Translocation of Protein Kinase
Nature reviews Mol Cell Biol. 13 B. Meier R et al 1997. JBC
Week-6
2012 (Shows how a newly identified
mTOR Signaling in Growth protein kinase is characterized;
Control and Disease Cell 149 including its regulation by
2012 phosphorylation and its
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localization)

Cytokine receptors and JAK/Stat Book A: 937-941 and 946-948 A major role for the protein
pathway Book B: 400-406 and 417-424 tyrosine kinase JAK1 in the
TGF signaling JAK/STAT signal transduction
Notch signaling pathway in response to
Week 7
interleukin-6. Guschin D EMBO J
14(7) 1995

Wnt signaling Book A: 948-952 Phosphorylation and Regulation

Hedgehog signaling Book B: 507-509 of Raf by Akt (Protein Kinase B)
Signaling cross talk Zimmermann et al Science 286
Week 8
1999
(Shows cross talk between Akt
and Raf-MEK-Erk pathway)
Apoptosis Book A: Chapter 17 and 18 Sequential activation of ICE-like
Regulation of cell cycle Book B: 429-466 and 511-530 and CPP32-like proteases during
Fas-mediated apoptosis Enari M
et al Nature 380 1996.
Week 9 (Using specific inhibitors, this
paper shows that Fas induced
apoptosis requires sequential
activation of caspases)

Toll like receptor signaling Book A: 952-954
NFkB pathway Book B: 111-113
The role of pattern-recognition
receptors in innate immunity:
Week 10
update on Toll-like receptors.
Nature Immunology 11(5) 2010
Deregulation of signaling in human Book B: 469-507
disease Hallmarks of Cancer: The Next
Hallmarks of cancer I Generation Cell 144(5) 2011
Week 11
Hallmarks of cancer II Book B: 469-507
Oncogenes and tumour suppressors Hallmarks of Cancer: The Next
Generation Cell 144(5) 2011
Week 12
Targeting signaling proteins for cancer
therapeutics The story of Imatinib (Gleevec)
Week 13
Case studies: Success and challenges (Papers will be given after the
half term
The innate immune response to
bacterial flagellin is mediated
by Toll-like receptor 5. Hayashi F
et al Nature 410 2001
(This article identifies flagellin as
target of TLR5 and describes
experiments to validate it as a
target)
Intratumor heterogeneity and
branched evolution revealed by
multiregion sequencing Gerlinger
M N Engl J Med 366(10) 2012
(Shows how tumours evolve with
multiple mutations)
Binding of ras to
phosphoinositide 3-kinase
p110alpha is required for ras-
driven tumorigenesis in mice.
Gupta S Cell 129(5) 2007
(Shows how functions of
oncogenes are studied in whole
organism, mice in this case)
A novel, selective, and efficacious
nanomolar pyridopyrazinone
inhibitor of V600EBRAF Whittaker
S et al Cancer Research 70(20)
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2010

Student presentations TBA

Week 14

Textbook(s)/Supplementary Readings
(A) Molecular Biology of the Cell (Alberts et al. 2008 - 5th Edition).
(B) Biochemistry of signal transduction and regulation (Gerhard Krauss 3rd edition 2003 or 4th edition 2008)
(C) Online resource for cell signaling biology: http://www.biochemj.org/csb/ (Most of the topics covered in this outline are
present in this resource, students are strongly encouraged to read through the books and this online resource before and after
the lecture)