GMS 6647:  Transcriptional and Translational Control of Cell Growth and Proliferation

Course Director: Daiqing Liao, Ph.D. (dliao@ufl.edu, phone: 294-7976)
Fall 2005, 3rd Module
Mon and Wed, 2:00-3:30 pm
Room: R4-265

Course description

This course is designed for the 1st and 2nd year IDP students to learn fundamental mechanisms that govern cell growth and proliferation. Two cellular mechanisms, transcription and translation, are critically involved in control of gene expression. Transcription and translation control gene expression at the mRNA and protein level respectively.

Until recently, the translational machinery is regarded as a protein production factory that has little regulatory roles. Advances in recent years have revealed fundamental roles of the translational machinery in regulating cell growth and proliferation. Therefore, it is timely that students are given a more comprehensive view regarding control of gene expression at both transcriptional and translational levels.

The genomic sequences of human and many other organisms have been determined, and thousands of genes are identified. The differential expression of these genes controls normal cellular processes, abnormal processes associated with diseases and cellular responses to environmental challenges. Advanced understanding of these processes requires conceptual knowledge and experimental approaches regarding molecular mechanisms regulating gene transcription. The course reviews some basic concepts of gene transcription, but will emphasize on new conceptual and experimental advances in the latest literature regarding molecular mechanisms of gene transcription as well as molecular mechanisms underlying abnormal gene transcription associated with diseases especially cancer.

Recent studies using genomic and proteomic techniques indicate that there is a large discrepancy between mRNA and protein levels in cells. It is now widely appreciated that translation and posttranslational events play critical roles in control of gene expression. Translation also plays a role in regulating development, cellular responses to extracellular stimuli. Cellular translational control is perturbed during viral infection and in diseases. The course begins with a brief introduction of basic knowledge of translational machinery, and continues with lectures and literature reviews and discussions on translational control in cellular stress response, subversion of cellular translation process during viral infection and the relati onship between translational control and cancer.

Course outline:
Introduction to transcription
Promoters, and general transcriptional machinery
Activators, coactivators, and repressors and corepressors
Enhancers and cis-acting DNA elements
Epigenetic control of gene transcription
Histone modifications (acetylation, deacetylation, methylation, phosphorylation etc.)
DNA methylation
Control of gene transcription by tumor suppressors
p53 as a transcriptional activator
Regulation of p53-mediated transcription
Rb as a transcription repressor
Viral oncogenes in the control of gene transcription
Viral oncogenes in transcriptional activation
Viral oncogenes in transcriptional repression
Introduction to translational control of gene expression
Ribosome and translational mechanisms
Translational control of developmental decisions
Translational control in signal transduction
Translational control during stress
Translational control in heat shock
Endoplasmic reticulum stress and translational control
Viral translational strategies
Modification of translational apparatus by viruses
Double-stranded RNA activated protein kinase PKR pathway
Adenovirus subversion of cellular protein synthesis
Translational control and cancers
Oncogenes in regulation of translation
Targets and mechanisms for the regulation of translation in malignant transformation
Ribosomal components in tumor suppression mechanisms

* No textbook will be used. Journal articles or handouts will be distributed.

* Grading scale: letter grade

60% Oral presentation and group discussion--A selected published paper will be presented and discussed in the class. The presenter will introduce background and rationale for the study, show the data that support the author’s point of view and summarize the major conclusions of the paper. The presenter is also encouraged to critique the paper, point out the weakness and offer points for improvement.

40% A final report -- The report will be a review of the literature within the topics covered in this course. Each student will choose a topic based on his/her interest and write a review of recent development and identify potential areas of interests for future studies. The report should include references. Figures can be included, but are optional. The report will be 5 double-spaced pages typed in a 12 pt font, excluding references and figures. The report is due at the last day of the course.

Student comments from the Fall 2004 Semester: This course was very useful to me. Most of the papers were appropriate and the course was set up in a way where we could easily discuss things as a group.