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7.60 Cell Biology: Structure and Functions of the Nucleus

Spring 2006

Graphic illustration of a cell nucleus.Graphic illustration of a cell nucleus. (Image courtesy of the U.S. National Library of Medicine.)

Course Highlights

This course features a bibliography of readings.

Course Description

This course covers the fundamentals of nuclear cell biology as well as the methodological and experimental approaches upon which they are based. Topics include Eukaryotic genome structure, function, and expression, processing of RNA, and regulation of the cell cycle. The techniques and logic used to address important problems in nuclear cell biology is emphasized. Lectures cover broad topic areas in nuclear cell biology and class discussions focus on representative papers recently published in the field.



Syllabus

Course Description

The goal of this course is to teach both the fundamentals of nuclear cell biology as well as the methodological and experimental approaches upon which they are based. Class meetings at the start of the week will generally be lectures describing the background and fundamental findings in a particular area of nuclear cell biology. The second session class meetings of the week will generally be a group discussion of one assigned paper in the same area. These seminal papers are used to understand both the important elements of the field as well as to provide concrete examples of the experimental approaches and logic used to establish these findings. Two students will be assigned to present the paper for each discussion based class and faculty and students will participate in the discussion. All students will be expected to have read the paper under consideration and be prepared for a lively discussion.

Enrollment is open to all biology graduate students and undergraduates by permission.



Evaluation

Students will be evaluated by two criteria. Participation in class discussions will constitute 50% of the grade. The remaining 50% of the evaluation will be based on a written proposal due at the end of the semester.


ACTIVITIESPERCENTAGES
Class Discussions50%
Written Proposal50%




Calendar

PAS = Prof. Phillip Sharp
RAY = Prof. Richard A. Young


SES #TOPICSLECTURERS
1Introduction: NucleusRAY
2Lecture: GenomeRAY
3Discussion: Genome
4Lecture: Cell Cycle ControlRAY
5Discussion: Cell Cycle Control
6Lecture: Transcription Apparatus and RegulatorsRAY
7Discussion: Transcription Apparatus and Regulators
8Lecture: Chromatin and Gene Expression IPAS
9Discussion: Chromatin and Gene Expression I
10Lecture: Chromatin and Gene Expression IIRAY
11Discussion: Chromatin and Gene Expression II
12Lecture: Genome Replication/RepairGuest Lecturer: Prof. Angelika Amon
13Discussion: Genome Replication/Repair
14Lecture: Nuclear Structure, Import/ExportPAS
15Discussion: Nuclear Structure, Import/Export
16Lecture: DNA Modification/EpigeneticsGuest Lecturer: Prof. Rudy Jaenisch
17Discussion: DNA Modification/Epigenetics
18Lecture: Alternative Splicing/PolyadenylationPAS
19Discussion: Alternative Splicing/Polyadenylation
20Lecture: Signal TransductionRAY
21Discussion: Signal Transduction
22Lecture: RNA Interference I - Silencing and microRNAsPAS
23Discussion: RNA Interference I - Silencing and microRNAs
24Lecture: RNA Interference II - TranscriptionPAS
25Discussion: RNA Interference II - Transcription
26Course Review: Group Discussion




Readings

SES #TOPICSREADINGS
3Discussion: GenomeLindblad-Toh, K. et al. "Genome sequence, comparative analysis and haplotype structure of the domestic dog." Nature 438 (2005): 803-819.
5Discussion: Cell Cycle ControlMalumbres, M., R. Sotillo, D. Santamaria, J. Galan, A. Cerezo, S. Ortega, P. Dubus, and M. Barbacid. "Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6." Cell 118 (2004): 493-504.
7Discussion: Transcription Apparatus and RegulatorsSpilianakis, C.G., Lalioti, M.D., Town, T., Lee, G.R., and Richard A. Flavell, R.A. "Interchromosomal associations between alternatively expressed loci." Nature 435 (2005): 637-645.
9Discussion: Chromatin and Gene Expression ISchmitt, S., M. Prestel, and R. Paro. "Intergenic transcription through a polycomb group response element counteracts silencing." Genes Dev 19 (2005): 697-708.
11Discussion: Chromatin and Gene Expression IICarrozza, M.J. et al. "Histone H3 Methylation by Set2 Directs Deacetylation of Coding Regions by Rpd3S to Suppress Spurious Intragenic Transcription." Cell 123 (2005): 581-592.
13Discussion: Genome Replication/RepairUhlmann, F., D. Wernic, M. A. Poupart, E. V. Koonin, and K. Nasmyth. "Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast." Cell 103 (2000): 375-386.
15Discussion: Nuclear Structure, Import/ExportGerber, A. P., D. Herschlag, and P. O. Brown. "Extensive association of functionally and cytotopically related mRNAs with Puf family RNA-binding proteins in yeast." PLos Biol 2 (2000): E79.
17Discussion: DNA Modification/EpigeneticsMager, J., Montgomery, N.D., Pardo-Manuel de Villena, F., and Magnuson, T. "Genome imprinting regulated by the mouse Polycomb group protein Eed." Nature Genetics 33 (2003): 502-507.
19Discussion: Alternative Splicing/PolyadenylationHan, K., G. Yeo, P. An, C. B. Burge, and P. J. Grabowski. "A combinatorial code for splicing silencing: UAGG and GGGG motifs." PLoS Biol 3 (2005): E158.
21Discussion: Signal TransductionSimone, C., Forcales, S.V., Hill, D.A., Imbalzano, A.N., Latella, L., and Puri, P.L. "p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci." Nature Genetics 36 (2004): 738-743.
23Discussion: RNA Interference I - Silencing and microRNAsStark, A., J. Brennecke, N. Bushati, R. B. Russell, and S. M. Cohen. "Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3'UTR Evolution." Cell 123 (2005): 1133-1146.
25Discussion: RNA Interference II - TranscriptionVerdel, A., S. Jia, S. Gerber, T. Sugiyama, S. Gygi, S. I. Grewal, and D. Moazed. "RNAi-mediated targeting of heterochromatin by the RITS complex." Science 303 (2004): 672-676.

Sugiyama, T., H. Cam, A. Verdel, D. Moazed, and S. I. Grewal. "RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production." Proc Natl Acad Sci 102 (2005): 152-157.
26Course Review: Group Discussion




Assignments

Written Proposal

A written proposal is due at the end of the semester. The proposal will be a short (5 double-spaced pages or less, 12 pt Times), critical description of an experimental approach to address a topic covered in class.

An ideal proposal would briefly describe the experimental system and the issue to be addressed, outline a single experimental approach with appropriate controls to assess one aspect of this issue, describe possible outcomes and potential problems of the proposed experiment, and discuss conclusions that could be made based upon the possible outcomes.




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