MCDB 4426 - Spring 2009

Cell signaling and developmental regulation

 

B121 of Porter Biosciences,

Tuesdays/Thursdays, 2:00-3:15 PM

 

Lecturer:

Dr. Ding Xue

E-mail: ding.xue@colorado.edu

 

Syllabus:

 

Jan-13 Tues.  Introduction lecture:  Course organization, general introduction, goals of the class and roles of cell signaling events.  PPT

Recommended reading material: Chapter 15 (Cell Communication) in Molecular Biology of the Cell by Alberts et al. 2002, 4th Edition.  Review other chapters as you need.  This book is very useful for this class.  In addition, we will use the i-clicker system to foster discussions during some of the lectures and paper discussions. If you have an i-clicker, please bring it to the class. If you donŐt have one, please buy one from the CU Bookstore or borrow one.

 

Cell Signaling in C. elegan embryonic development

 

Jan-15 Thurs.  Lecture: Embryo Development.  PPT

Read Alberts Book Page 1050-1059, page 1114-1119, page 1067-1070, page 1077–1102, to have an idea about various organisms.

Han M (1997). Gut Reaction to Wnt Signaling in Worms.  Cell 90, 581-584. PDF

 

Jan-20 Tues.  Paper Discussion

Goldstein B (1992).  Induction of gut in Caenorhabditis elegans embryos.  Nature 357:255-257.  PDF  PPT

 

Jan-22 Thurs. Paper Discussion

Mello CC, Draper BW, Priess JR (1994).  The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo.  Cell 77:95-106.  PDF

 

Jan-27 Tues. Paper Discussion

Thorpe CJ, Schlesinger A, Carter JC, Bowerman B (1997). Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell 90:695-705.  PDF

 

Notch Pathway

Read the following reviews:

 

Fiœza UM, Arias AM (2007).  Cell and molecular biology of Notch.  J Endocrinol 194:459-474.  PDF

 

Bray SJ (2006). Notch signalling: a simple pathway becomes complex.  Nat Rev Mol Cell Biol. 7:678-689. PDF

 

Jan-29 Thurs. Paper Discussion

Struhl G, Fitzgerald K, Greenwald I (1993).  Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.  Cell 74:331-45.  PDF

 

Feb-3 Tues. Paper Discussion

Levitan D, Greenwald I (1995). Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377:351-354.  PDF

 

Feb-5 Thurs. Paper Discussion

Pan D, Rubin GM (1997).  Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 90:271-280.  PDF

 

Feb-10 Tues.  Paper Discussion

Mumm JS et al (2001).  A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1.

Mol Cell 5:197-206.  PDF

 

Small RNA-mediated cell signaling

Read the following review:

Mello CC and Conte D (2004). Revealing the world of RNA interference.  Nature 431:338-342. PDF

 

Feb-12 Thurs. Paper Discussion

Fire A et al (1998).  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.  Nature 391:806-811.  PDF

 

Feb-17 Tues. Paper Discussion

Bernstein E et al. (2001).  Role for a bidentate ribonuclease in the initiation step of RNA interference.  Nature 409:363-366.  PDF

 

Feb-19 Thurs. Paper Discussion

Elbashir et al. (2001).  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.

Nature 411:494-498.  PDF

 

Feb-24 Tues.  Lecture:  Overview of programmed cell death and its genetic basis.  PPT

         Readings: Danial, N. N., and Korsmeyer, S. J. (2004). Cell death: critical control points.  Cell 116, 205-219.  PDF

         Adams, J. M. (2003). Ways of dying: multiple pathways to apoptosis. Genes Dev 17, 2481-2495.  PDF

 

Feb-26 Thurs.  Paper Discussion: Genetic basis of PCD I – Genetic identification of cell death genes

         Hedgecock, E. M., Sulston, J. E., and Thomson, J. N. (1983). Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 220, 1277-1279.  PDF

          

Mar-3 Tues.  Paper Discussion: Genetic basis of PCD II – Genetic identification of cell death genes

         Ellis, H. M., and Horvitz, H. R. (1986). Genetic control of programmed cell death in the nematode C. elegans. Cell 44, 817-829.  PDF

 

Take home exam (exam questions will be distributed by e-mail on March 6 and please return your answers in four days) 

 

Mar-5 Thurs. Paper Discussion: Biochemical basis of PCD I

         Liu, X., Kim, C. N., Yang, J., Jemmerson, R., and Wang, X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c.  Cell 86, 147-157.  PDF

  

TGF-§ signaling pathway (Taught by Dr. Xuedong Liu) 

Read the following reviews:

 

Clarke, D.C. and Liu, X. (2008). Decoding the quantitative nature of TGF-beta/Smad signaling. Trends Cell Biol. 18:430-442.  PDF

 

MassaguŽ J (1998).  TGF-beta signal transduction.  Annu Rev Biochem. 67:753-791.  PDF

 

Mar-10 Tues.  Lecture  PPT

 

Mar-12 Thurs.  Paper discussion:

Inman GJ, Nicol‡s FJ, Hill CS (2002).  Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity.   Mol Cell 10:283-294.  PDF

 

Mar-17 Tues.  Paper Discussion:

Lin et al. (2006).  PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell 125:915-928.  PDF

 

Mar-19 Thurs. Paper Discussion: Biochemical basis of PCD II

         Zou, H., Henzel, W. J., Liu, X., Lutschg, A., and Wang, X. (1997). Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90, 405-413.  PDF

                                                                                                                                                

Mar-31 Tues.  Lecture:  Life vs. death responses of a cell to extracellular signals.  PPT

         Readings: Nagata S (1997).  Apoptosis by death factors.  Cell 88: 355-365.  PDF

 

Apr-2 Thurs.  Paper Discussion:  Signals for death I-- Fas/TNF-induced apoptosis

         Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM (1995).  FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.  Cell 81: 505-512.  PDF

 

Arp-7 Tues. Paper Discussion:  Signals for death II—Caspase cascade

         Muzio et al. (1996).  FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.  Cell 85: 817-827.  PDF

 

Apr-9 Thurs.  Paper Discussion:  Signals for death III—Cell surface to mitochondria to caspase activation

         Luo, X., Budihardjo, I., Zou, H., Slaughter, C., and Wang, X. (1998).  Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.  Cell 94, 481-490.  PDF

         Li, H., Zhu, H., Xu, C.J., and Yuan, J. (1998). Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501.  PDF

 

Apr-14 Tues.  Paper Discussion:  Signals for death IV—Genotoxic stresses.

         Nijhawan D, Fang M, Traer E, Zhong Q, Gao W, Du F, Wang X (2003).  Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation.  Genes Dev. 17:1475-1486.  PDF

 

Apr-16 Thurs. Lecture: Signals for removal of apoptotic cells.  PPT

         Readings: Conradt, B. and Xue, D. (2005). Programmed cell death. WormBook, ed. The C. elegans Research Community.  WormBook, doi/10.1895/wormbook.1.32.1. PDF

Savill, J., and Fadok, V. (2000). Corpse clearance defines the meaning of cell death. Nature 407, 784-788.  PDF

 

Apr-21 Tues. Discussion:  Signals for death V-- Pathways for the removal of dead cells.

         Zhou, Z., Hartwieg, E., and Horvitz, H. R. (2001). CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104, 43-56.  PDF

 

Apr-23 Thurs.  Discussion:  Signals for death VI-- Pathways for the removal of dead cells.

         Wang et al. (2003).  Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12. Science 302, 1563-1566.  PDF

 

Apr-28 Tues. Prepare for the final exam.

 

Apr-30 Thurs.  TBD.

                       

 

Requirements for students:  

This is a different kind of course from those you have taken earlier.  This course is designed to teach students the experimental approaches to solve scientific problems.  Students will learn how a scientific problem is raised and how the problem is approached.  This goal will be achieved by:

 

1.  The lectures will not simply be stating the facts.  The scientific thinking process will be introduced to the students.  The students are required to read some research papers/review articles/book chapters before or after each lectures.  These articles will be made available to the students on the course website.

 

2.  There will be oral presentations and discussions about original research papers by each student during the semester.  The oral presentation and discussion will include the followings: (a) the background of the research, (b) the questions that the paper addressed, (c) all figures and tables, (d) discussion of key research experiments, (e) conclusions from the results, and (f) additional or future experiments that can be pursued.  Each paper should be read and discussed by all students.  I will randomly pick a student or students can volunteer to lead the one of the discussions.  Alternatively, I will display i-clicker questions for the whole class to discuss.

 

Each article should be read carefully and critically by all students before the presentation/discussion sessions. 

 

3.  The students are required to actively participate in the discussions.  In the presentation and discussion sessions, the discussion will be focused on the papers presented.   Students are also encouraged to ask questions throughout the lectures.  You will learn from papers, lectures, paper presentations of your own and your classmates.  

 

4.  The students are required to take two exams (in class or take home) during the semester.

 

5.  Reading related chapters from several cell biology or developmental biology textbooks should help.  Molecular Biology of the Cell by Alberts et al. (2002) is one of the best.  You may copy just related chapters, or it is available in searchable format online at the PubMed site (in the books section).  For the best results, try to do relevant reading before the classes and after.  For some sessions, particularly those presentation/discussion sessions, advanced reading is required.

 

The required readings are original research articles and some review articles.  References and copies of the articles will be provided on the course website. 

 

Grading

Grades will be determined on the basis of the exams (50%), presentation of papers and participation in classroom discussion (40%), and attendance (10%). Grading in presentation and participation in discussion will emphasize whether you have read the papers carefully such that you can present the figures clearly and logically and your willingness to discuss them more than the clarity of how you present and discuss information. In other words, our emphasis is on getting you to think about, criticize, interpret, and discuss scientific experiments without being intimidated about speaking up.  

 

Because this is a small presentation/discussion class, being in the classroom itself is the major part of the study. Students should make every effort to show up for every class, particularly when your classmates are presenting and discussing papers.  Attendance will be taken and counted in the grade.

 

Exams will cover concepts from both lectures and papers discussed, and may include questions relating to the design of possible next experiments based upon a paper covered in class, or precisely what can be concluded from the data in a specific experiment (hypothetical or actual).