BISC403 Advanced Molecular Biology Fall 2005 Course Syllabus p. 1 of 4 DRAFT _____ SUBJECT TO CHANGE FINAL VERSIONWILL BE POSTED ON BLACKBOARD Lectures: TTh 12.30 - 1.50, THH114 Discussion: Tue 2-3.50, ZHS360 Weds 2-3.50, GFS108 Professors: Prof. Susan Forsburg, Office: RRI 104C Office hours: by appointment Tel/vox: (213) 740-7342, email: forsburg@usc.edu Prof. John Tower Office: RRI 219C Office hours: Thurs 2-4 Tel/vox: (213) 740-5384 email: jtower@usc.edu TA: Pao-Chen Li Office: RRI 108 Office hours: Tue 4-5 (RRI-202) tel/vox: 740-5558 email: paochenl@usc.edu Lectures readings and course notes on Blackboard. Prerequisites: BISC311 or BISC 320L (Molecular Biology) is a firm prerequisite for this course. Objective: The course objective is to consider a few topics in Molecular Biology in depth. Topics are chosen by the teaching faculty and generally represent active areas of their current research. The course also requires reading primary research papers for discussion. Format: There is no required textbook for this course. You will receive digital copies of lecture handouts and reading materials. Resources and review articles will also be uploaded to Blackboard (blackboard.usc.edu). Background reading in any general Genetics, Cell Biology, or Molecular Biology textbook may be helpful. Discussion Sessions: Participation is required for full points in the course. Each week the professor will assign a relevant research paper related to that week’s lectures. Students should be prepared to participate in a journal club about that paper, which will require reading the paper and any background prior to discussion. Students will be randomly called upon to present background materials, or discuss any figure of the paper or method employed, and credit will be awarded for this presentation. Additional points will be awarded for active participation in discussion. This will account for approximately 20% of your grade. BISC403 Advanced Molecular Biology Fall 2005 Course Syllabus p. 2 of 4 Date Subject Professor SECTION I: EPIGENETICS (Prof Forsburg) Tues Aug 26 Introduction to Chromosomes Forsburg Thurs Aug 28 Histones and nucleosomes Forsburg Week 1 Background reading: Olins DE, Olins AL. Chromatin history: our view from the bridge. Nat Rev Mol Cell Biol. 2003 4:809-14. Khorasanizadeh S, (2004) The nucleosome: from genomic organization to Genomic regulation. Cell 116: 259. Read pages 259-262 (we will be using sections of this review throughout the course) Discussion paper: Randall and Kelly TJ The fate of parental nucleosomes during SV40 DNA replication. J Biol Chem. 1992 Jul 15;267(20):14259-65. Wk 2 Tues Sept 2 Nucleosome assembly Forsburg Thurs Sept 4 Chromatin remodeling I Forsburg Week 2 Background reading Khorasanizadeh S The nucleosome: from genomic organization to Genomic regulation. Cell 116: 259. (2004) Read pages 267-269 (ATP remodeling section) Saha A, Wittmeyer J, Cairns BR Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol. 2006 Jun;7(6):437-47. Review . Discussion paper: Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science. 2003 Aug 22;301(5636):1090-3. See comment Svejstrup JQ. Transcription. Histones face the FACT. Science. 2003 Aug 22;301(5636):1053-5. Wk 3: tues Sept 9 Chromatin remodeling II; histone Forsburg modifications I Thurs Sept 11 Histone Modifications II Forsburg Week 3 Background reading Khorasanizadeh S The nucleosome: from genomic organization to Genomic regulation. Cell 116: 259. (2004) Read pages 263-267 Peterson CL and Laniel MA Histones and Histone modifications Curr Biol 14: R546-51 Lee KK, Workman JL. Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol. 2007 Apr;8(4):284-95. Review. Discussion paper: Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci U S A. 1964 May;51:786-94. Wk 4: Tues Sept 16 Recognition of Histone Forsburg modifications. Histone variants. Thurs Sept 18 Midterm I Forsburg Background reading Week 4 Khorasanizadeh S The nucleosome: from genomic organization to Genomic regulation. Cell 116: 259. (2004) Read pages 269-270 Sarma K and Reinberg D, Histone Variants meet their match. Nat Rev Mol Cell Biol 6:139-149 (2005) De la Cruz X, Lois S, Sanchez-Molina S, Martinez-Balbas MA (2005) Do protein motifs read the histone code? Bioessays 27:164-175 BISC403 Advanced Molecular Biology Fall 2005 Course Syllabus p. 3 of 4 Discussion paper: week 4 Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 2001 Mar 1;410(6824):120-4. Wk 5 Tues Sept 23 Case study: DNA damage response Forsburg Thurs Sept 25 Case study: heterochromatin and Forsburg silencing Background reading Week 5 Downs JA, Nussenzweig MC, Nussenzweig A.Chromatin dynamics and the preservation of genetic information. Nature. 2007 Jun 21;447(7147):951-8. Review. Grewal SI, Jia S. Heterochromatin revisited. Nat Rev Genet. 2007 Jan;8(1):35-46. Review. Discussion paper: Lan F, Zaratiegui M, Villen J, Vaughn MW, Verdel A, Huarte M, Shi Y, Gygi SP, Moazed D, Martienssen RA, Shi Y. S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription. Mol Cell. 2007 Apr 13;26(1):89-101. Wk 6: Tues Sept 30 Case study: Centromeres and Forsburg chromosome segregation Thurs Oct 2 RNAi Background reading Week 6 Grewal SI, Elgin SC. Transcription and RNA interference in the formation of heterochromatin. Nature. 2007 May 24;447(7143):399-406. Review. Discussion paper: Mizuguchi G, Xiao H, Wisniewski J, Smith MM, Wu C. Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes. Cell. 2007 Jun 15;129(6):1153-64. Wk 7: Tues Oct 7 DNA methylation Forsburg Thurs Oct 9 MIDTERM II Forsburg Background reading Week 7 Khorasanizadeh S The nucleosome: from genomic organization to Genomic regulation. Cell 116: 259. (2004) Read pages 267 Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators Trends Biochem Sci. 2006 Feb;31(2):89-97. Discussion paper: Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003 Jul 15;13(14):1192-200. SECTION II: AGING (Prof Tower) Wk 8: Tues Oct 14 Models of aging Tower Thurs Oct 16 Models of aging Tower Week 8 Background reading: Hughes, K. A. and R. M. Reynolds, 2005. Evolutionary and mechanistic theories of aging. Annu Rev Entomol 50, 421-45. Muller, F. L., M. S. Lustgarten, Y. Jang, A. Richardson and H. Van Remmen, 2007. Trends in oxidative aging theories. Free Radic Biol Med 43, 477-503. BISC403 Advanced Molecular Biology Fall 2005 Course Syllabus p. 4 of 4 Week 8 Discussion paper: Yoshida, K., T. Fujisawa, J. S. Hwang, K. Ikeo and T. Gojobori, 2006. Degeneration after sexual differentiation in hydra and its relevance to the evolution of aging. Gene 385, 64-70. Wk 9: Tues Oct 21 Mortality Tower Thurs Oct 23 Gene expression during aging Tower Week 9 Background reading: Partridge et al (2005) Dietary restriction, mortality trajectories, risk and damage. Mech Age Dev 126:35-41. Week 9 Discussion paper: Mair et al (2003) Demography of Dietary Restriction and Death in Drosophila. Science 301:1731 Wk 10: Oct 28 Oxidative stress and damage Tower Thurs Oct 30 Oxidative stress and damage Tower Week 10 Background reading: Partridge et al (2005) Sex and Death: What is the Connection? Cell 120:461472. Week 10 Discussion paper: Giannakou et al (2007) Dynamics of the action of dFOXO on adult mortality in Drosophila. Aging Cell 6:429-438. Wk 11: Tues Nov 4 Mitochondria Tower Thurs Nov 6 MIDTERM III Tower Week 11 Background reading: Kujoth and Prolla (2008) Evolving insight into the role of mitochondrial mutations in aging. Exp Gero 43:20-23. Week 11 Discussion paper: Vermulst et al (2008) DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nature Genetics 40:392 Wk 12: Tues Nov 11 Stem cells Tower Thurs Nov 13 Cellular senescence, telomeres Week 12 Background reading: Brack and Rando (2007) Intrinsic Changes and Extrinsic Influences of Myogenic Stem Cell Function During aging. Stem Cell Rev 3:2260237. Week 12 Discussion paper: Conboy et al (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760-764. Wk 13: Tues Nov 18 Cellular senescence, telomeres Tower Thurs Tues Nov 20 Progerias Tower Week 13 Background reading: Martin et al (2007) Genetic determinants of human health span and life span: progress and new opportunities. PLOS Genetics 3:e125. Discussion paper: Scaffidi, P. and T. Misteli, 2006. Lamin A-dependent nuclear defects in human aging. Science 312, 1059-63. Wk 14: Tues Nov 25 Sirtuins, DR and IIS Tower Thurs Nov 27 THANKSGIVING Week 14 Background reading: Kondratov, R. V. 2007 A role of the circadian system and circadian proteins in aging. Ageing Research Reviews 6:12-27.Week 14 Discussion paper: Chen, Z., E. A. Odstrcil, B. P. Tu and S. L. McKnight, 2007. Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity. Science 316, 1916-9. Wk 15: Tues Dec 2 Replicators and Game theory, SAP Tower Thurs Dec 4 Circadian Rhythms Week 15 Discussion paper: Koh, K., J. M. Evans, J. C. Hendricks and A. Sehgal, 2006. A Drosophila model for age-associated changes in sleep:wake cycles. Proc Natl Acad Sci U S A 103, 13843-7. Dec XXX FINAL BISC403 Advanced Molecular Biology Fall 2005 Course Syllabus p. 5 of 4 Grading: Midterm I 100 pts Midterm II 100 pts Midterm III 100 pts Final 100pts Discussion participation: 100 pts TOTAL = 500 pts Letter grades are determined by a curve based upon total points. Other Policies: 1. Exam dates are firm. If a student misses an exam due to a true emergency(with an acceptable written excuse; written information concerning a death in the family must be provided), we MAY schedule a make-up exam, or at our discretion MAY permit the use of the average of other exams in determining the course grade. No one will be admitted to an exam after the first student has left the exam. 2. Regrading of exams will be done only by the professor who wrote the question. Regrading can only be done within one week of the day the exam is initially returned to the class. 3. No special assignments for extra credit are given. 4. Final exams will be kept in Dr. Forsburg’s office for the required period. 5. Academic integrity policies of the university will be strictly followed. Infractions can result in severe penalties. See SCampus for these policies. 6. It may be necessary to make some adjustments in the syllabus during the semester. 7. Disability: Students requesting academic accommodations based on a disability are required to register with Disability Services and Programs (DSP) each semester. A letter of verification for approved accommodations can be obtained from DSP when adequate documentation is filed. Please be sure the letter is delivered to Dr. Tower or Dr. Forsburg as early in the semester as possible. DSP is open Mon-Fri, 8:30-5:00. The office is in Student Union 301 and their phone number is 740-0776.