Download BISC 6274 - GWU Biology Department

GENE REGULATION AND GENETIC ENGINEERING
(BiSc 6274)
Brief Description: A survey of gene regulation in bacteria, yeast and eucaryotes with an
emphasis on epigenetic mechanisms of the control of gene expression.
Course Objectives: 1) introduce students to bodies of knowledge and traditions of inquiry
that had not previously been part of their experience, in both lecture and discussion formats;
and 2) equip those same students with the analytical skills - of argument, experimental
modeling, laboratory procedure – that will enable them to move confidently within those
traditions and to engage in independent research after a course is over.
Syllabus, Fall 2011
Part One: General Principles of Gene Regulation
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A brief history gene regulation. The classic experiments of Jacob Monod and Lwoff and
the Operon Theory of gene regulation.
Principles of protein-DNA interactions.
Experimental methods for studying protein-DNA interactions.
Learning Outcomes
Students will:
1. Be reminded of the operon theory and its place in modern studies on gene regulation.
2. Be made aware of the principles of, and methods used to study, protein-DNA
interactions.
3. Be able to analyze and interpret research data relating to these studies.
Part Two: Operons and Gene Regulation in Prokaryotes
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Gene structure and expression in bacteria. The molecular mechanisms of induction and
repression. The lac and trp operons in Escherichia coli.
A survey of operons and regulons in prokaryotic gene regulation.
The regulation of virulence and lysogeny in bacteriophage.
Anti-termination and attenuation in bacteria.
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Bacterial riboswitches.
Learning Outcomes
Students will
1. Have an extensive knowledge of operon systems in bacteria with selected examples; and
understand molecular techniques for studying gene control in bacteria.
2. Be able to use the literature to survey the role of operons and regulons in the control of
bacterial metabolism, virulence, osmoregulation and growth.
3. Learn about the mechanisms of attenuation in gram-positive and gram-negative
bacteria, including the importance of riboswitches in the latter.
4. Be able to analyze research data in primary papers on bacterial gene regulation.
Part Three: “Epigenetic” Mechanisms of Regulation in Bacteria
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Regulatory mechanisms of phosphotransferase systems (PTS) and two-component
signal transduction in bacteria.
“Global” mechanisms of metabolic regulation in bacteria.
Regulation of virulence in pathogenic bacteria
The regulation of cellular and colonial differentiation in bacteria: sporulation in Bacillus
subtilis and cellular asymmetry in Caulobacter cresescens.
Learning Outcomes
Students will:
1. Be aware of the cellular processes involved in the control of gene expression in bacteria
leading to metabolic adjustment, virulence and cell differentiation.
2. Appreciate the importance of “model” bacteria for studying the regulation of cell
differentiation in prokaryotic and eukaryotic cells.
3. Be able to write short but professional review essays based on literature searches on
selected topics in bacterial gene regulation.
Part Four: General Aspects of Gene Regulation in Eukaryotes
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Structure and expression of eukaryotic genes. Experimental methods for studying gene
expression in eukaryotic cells.
Transcription factors: positive and negative control.
Post-transcriptional, translational and post-translational aspects of gene regulation.
Learning Outcomes
Students will:
1. Be able to survey the mechanisms for gene control in lower and higher eucaryotes and
be aware of the major mechanisms of regulation that occur at all levels of gene
expression.
2. Comprehend and be able to analyze and interpret research data based on this kind of
research.
Part Five: The Role of Chromatin, DNA Methylation and RNAi in Eucaryotic Gene Regulation
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The regulation of genetic stability: Barbara McClintock’s controlling elements in maize,
and the “epigenetic” explanations of gene regulation.
Chromatin structure and its role in gene regulation.
Methylation, cellular differentiation and gene imprinting.
Interference RNA: the role of small RNAs (siRNA miRNA, etc.) in gene regulation.
Eukaryotic “model” organisms for studying gene expression: Saccharomyces cerevisiae
and Schizosaccharomyces pombe.
Gene regulation and development
Regulation of the cell cycle and cancer.
Learning Outcomes
Students will:
1. Understand the meaning of epigenetics and its importance in short-term and long-term
regulatory mechanisms of gene expression.
2. Know the structure of chromatin and how it is modified for gene expression.
3. Learn about patterns of DNA methylation and how they are involved in establishing
patterns of gene expression in development and differentiation, gene imprinting and
cancer.
4. Know about the use of model eukaryotic “model” organisms for studying gene
expression.
5. Be cognizant of the latest literature on all these aspects of gene regulation.
TEXTBOOKS
There are no required textbooks for this course. However, two are recommended:
Genes and Signals, by Mark Ptashne and Alexander Gann. Cold Spring Harbor Laboratory Press.
2002. You can download pictures from this book (as jpg or in pdf formats) at
www.genesandsignals.org/gs.php. Another useful set of figures (again in jpg and pdf formats)
are from Epigenetics and are available at www.genesandsignals.org/epigenetics.php.
Chromatin and Gene Regulation, by Bryan Turner. Blackwell Science. 2000.
Also, if your budget runs to it and you feel it may be useful for future classes and/or
comprehensive examinations, you may want to take a careful look at Genes X by B. Lewin et al.
Recommended readings of original papers and/or reviews will be provided for each topic. Most
of these will be made available on Blackboard in pdf format. PowerPoints shown in the lectures
will also be available on Files. Please check regularly for updates.
EXAMINATIONS
Three take-home examinations and two class presentations will be scheduled. Each
examination will consist of questions relating to data analysis and interpretation, experimental
design and short review topics.
INSTRUCTOR
David Morris. 349 Lisner Hall and 404 Bell Hall
Tel: 4-0996 and 4-3882; email: [email protected]
Office Hours: Friday, 9 until 12.