Spring 2006 - class starts on Wednesday, February 15th
SYLLABUS
Pre-requisites: GMS 6001 or consent of instructor.
Co-Directors: Daiqing
Liao, Ph.D. dliao@ufl.edu
Lei Xiao, Ph.D.
lxiao@ufl.edu
Expanded description: This course is designed to educate students on the many pathways of apoptosis and to train students to understand, present and critically analyze published articles in this field. This course will cover various aspects of the mechanisms and regulation of apoptosis (see Course Outline below). The course is offered on Mondays and Wednesdays in the ARB R4-265 at 9:00-10:30 AM. This course is designed to have nine classroom sessions (75-90 minutes) that will consist of a 45-60 minute lecture followed by a 30-minute discussion of an article to be chosen by the faculty. A PDF of the article will be emailed to each student the week before the scheduled class. One student will present the article, but all students are required to read the articles and to participate in the discussions. A quiz of 6-10 short answer questions will be handed out on Wednesday, March 20, and due back on Friday, March 22 in B1-006 before 5:00 PM.
Course Outline:
A. Introduction
1. Definitions: apoptosis versus necrosis
2. Developmental apoptosis
3. DNA damage and stress induced apoptosis
4. Pathogen-induced apoptosis
B. Stages of Apoptosis
1. Signaling Phase
a. External
b. Internal
c. DNA damage
2. Effector Phase
a. Cytochrome c
b. Caspases
c. Bax and Bak
3. Degradative Phase
a. Cytoplasmic changes
b. Nuclear changes
c. Phagocytosis
C. Methods for Measuring Apoptosis
1. Signaling Phase
2. Effector Phase
a. Caspase activity
b. Changes in mitochondrial permeability
3. Degradative Phase
a. Peripheral condensation of chromatin
b. DNA fragmentation (e.g. TUNEL)
c. Changes in cell surface phospholipids
D. Molecular Signals of Apoptosis
1. External Signals
a. FAS and TNF receptors
b. Caspase 8
2. Internal Signals
a. Mitochondria
b. Endoplasmic Reticulum
c. Nuclear envelop
d. Cytochrome c
e. Apaf-1 f. Caspase 9
3. DNA damage
a. p53
E. Molecular Effectors/Mediators of Apoptosis
1. Cysteine proteases
a. Caspases
b. Non-caspase cysteine proteases (e.g. calpains)
2. The Bcl-2 family of proteins
a. The anti-apoptotic members (e.g. Bcl-2 and Bcl-XL)
b. The pro-apoptotic members (e.g. Bax, Bak, Bad, and Bid)
3. The inhibitor of apoptosis proteins (IAPs)
F. Autophagy and Apoptosis
1. Autophagy: mechanisms and biological implications
2. Phagocytosis
G. Apoptosis in Cancer
1. Tumor suppressors
2. Oncogenes: inhibitors of apoptosis
H. Apoptosis in development
1. Physiological roles of apoptosis during development
2. Model organisms for studying apoptosis
No Textbook will be used. Instead we will use journal or handouts.
The class will consist of lecture and discussion of recent articles.
GMS6644 2006 Spring Semester Schedule
Room R4-265
Monday and Wednesday 9-10:30AM
| Date | Lecturer and lecture title | Student Presenter | Paper for presentation |
| Wednesday Feb. 15 | Lecture 1: Dr. Lei Xiao (Introduction) | Melissa Armas | Chipuk et al. Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis. Science. 303, 1010-1014 (2004) |
| Wednesday Feb. 15 | Lecture 1: Dr. Lei Xiao (Introduction) | Cory Lindsay | Opferman et al. Obligate Role of Anti-Apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells. Science. 307, 1101-1104 (2005) |
| Monday Feb. 20 | Lecture 2: Dr. Daiqing Liao (Mechanisms of Apoptosis) | Jeffrey Brower | Kuwana. et al., BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell. 2005 Feb 18;17(4):525-35. |
| Monday Feb. 20 | Lecture 2: Dr. Daiqing Liao (Mechanisms of Apoptosis) | Rebecca Loda | Hao, Z et al., Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell. 2005 May 20;121(4):579-91. |
| Wednesday Feb. 22 | Lecture 3: Dr. Brian Harfe (Apoptosis in Development) | Matthew Buzzeo | Sanz-Ezquerro, JJ and Tickle, C., Autoregulation of Shh expression and Shh induction of cell death suggest a mechanism for modulating polarising activity during chick limb development. Development 127, 4811-4823 (2000). |
| Monday Feb. 27 | Lecture 4: Dr. Lei Zhou (Radiation-mediated Apoptosis) | Shahnjayla Connors | Bradshaw, PS et al., Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nat Genet, 2005, 37(2):193-197. |
| Wednesday Mar. 1 | Lecture 5: Dr. Daiqing Liao (p53 and Apoptosis) | Patrick Corsino | Chipuk J. et al., PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science. 2005 Sep 9;309(5741):1732-5. |
| Wednesday Mar. 1 | Lecture 5: Dr. Daiqing Liao (p53 and Apoptosis) | Aleixo Santiago | Hemann MT et al., Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature. 2005 Aug 11;436(7052):807-11. |
| Monday Mar. 6 | Lecture 6: Dr. (DNA damage and Apoptosis) | Shangli Lian | Wu WS, Heinrichs S, Xu D, Garrison SP, Zambetti GP, Adams JM, Look AT. Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma. Cell. 2005 Nov 18;123(4):641-53. |
| Wednesday Mar. 8 | Lecture 7: Dr. W. Stratford May (Cell Death Pathways) | Songqing Li | Lakhani SA et al. Caspase 3 and 7: key mediators of mitochondrial events of apoptosis, Science, 311:847-851, 2006. |
| Monday Mar. 20 | Lecture 8: Dr. Lei Xiao (Drug Resistance and Apoptosis) | Jacqueline Sayyah | Sordella et al. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 305, 1163-1167 (2004) |
| Monday Mar. 20 | Lecture 8: Dr. Lei Xiao (Drug Resistance and Apoptosis) | Jeremy Flint | Villunger et al. p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa. Science. 302, 1036-1038 (2003) |
| Wednesday Mar. 22 | Lecture 9: Dr. William A. Dunn, Jr. (Autophagy-mediated Cell Death) | Darrell Hunt Amanda Waber |
Pattingre S. et al., Bcl-2 antiapoptotic proteins inhibits Beclin 1-dependent autophagy. Cell, 2005, Sept 23, 122:927-939. |
12/7/05