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MOLECULAR BIOLOGY AND BIOCHEMISTRY

Professors:  Anthony Infante, Donald Oliver

Associate Professors: Scott Holmes, Michael McAlear, Ishita Mukerji, Chair

Assistant Professors: Manju Hingorani, Robert P. Lane

 GRADUATE PROGRAM

Students in the Molecular Biology and Biochemistry Department study the molecular mechanisms of biological processes using the tools of molecular biology, genetics, biochemistry, and biophysics.

The graduate program of the Department of Molecular Biology and Biochemistry is designed to lead to the degree of doctor of philosophy. A master of arts degree is awarded only under special circumstances. The emphasis of the program is on an intensive research experience culminating in a thesis. The program of study also includes a series of courses covering the major areas of molecular biology, biochemistry, and biophysics, journal clubs in which current research is discussed in an informal setting, practica designed to introduce first-year students to the research interests of the faculty, and several seminar series in which distinguished outside speakers participate. The low student-faculty ratio allows programs to be individually designed and ensures close contact between the student and the faculty. All graduate students also have an opportunity to assist in teaching undergraduate courses. A concentration in molecular biophysics supported by a training grant from the National Institutes of Health is available for students with interest in both the physical and life sciences.  The department currently has 24 graduate students, and the graduate program is an integral part of the department offerings. Graduate students serve as teaching assistants in undergraduate courses and upper-level courses and seminars. Graduate students typically enjoy fruitful interactions with upper-level undergraduates performing research.

REQUIREMENTS FOR THE DOCTOR OF PHILOSOPHY DEGREE

Courses.  Ideally, incoming students will have completed courses in general biology, cell and molecular biology, genetics, biochemistry, general chemistry, organic chemistry, physical chemistry, calculus, and a computer language. Deficiencies in any of these areas would normally be made up in the first year. A core curriculum of graduate courses in the following areas is given on a two-year cycle: nucleic acid structure, biosynthesis and its regulation, regulation of gene expression, structural mechanisms and energetics of protein-nucleic acid interactions, protein structure and folding, protein trafficking in cells, physical techniques, molecular genetics, the cell cycle, biological spectroscopy and molecular, biochemical and cellular basis of cancer and other human diseases. Additional graduate course electives are also available. Within this general framework individual programs of study tailored to fit the student's background and interests are designed in consultation with the graduate committee and the student's advisor.

Qualifying examinations.  The criteria for admission to candidacy for the PhD will be performance in courses, aptitude for research, a written qualifying examination at the end of the third semester, and the oral defense of an original research proposal by the middle of the fourth semester.

Teaching.  Normally, three to four semesters of teaching are required.

Areas of Research. Research areas include the mechanisms of DNA replication and repair, centrosome and telomere function, gene regulation and DNA-protein interactions genome organization and structure, protein structure-function relationships, and protein trafficking between cell compartments.  These research topics are integral to our understanding of how cells become specialized during development, and how genes and proteins interact in genetic networks. A molecular/biochemical/biophysical-level approach to these topics will also contribute important medical insights. For example: 1) DNA replication, repair, and chromosome function are important fields for cancer research; 2) gene regulation and chromosome structure are important for stem cell biology; 3) protein structure-function relationships are critical for a host of neurodegenerative diseases; and 4) genetic pathways reveal consequences of mutations that underlie most genetics disorders. Our department is therefore focused on the fundamental genetic components of a cell, and our aim is to further understanding of how these components interact to produce complex phenotypes in the organism.

 

Facilites. The department is housed in a modern air-conditioned building.  Major times of instrumentation for molecular biological analysis include an Applied Biosystems DNA synthesizer, a microarray hybridization chamber, a Perkins-Elmer real time PCR machine, a gel-scanning densitometer/phosphorimager, and an Evans and Sutherland Picture System 350 for visualizing ethidium bromide-stained gels. Analytical instrumentation includes Varian400 and 500 MHz nuclear magnetic resonance (NMR) spectrometers, a laser Raman spectrometer with UV resonance Ruman capability, a time-correlated single photon counting flourescence setup, a ThermoElectron Deca XP Plus ion trap mass spectrometer equipped for reversed-phase electrospray tandem mass spectrometry, a Brechbuehler helium pressure cell for loading microcapillary columns, several UV-visible spectrometer, a stopped flow kinetics system, two high-performance liquid chromatography system, two standard steady-state fluorometers, and a Jasco circular dichroism (CD) spectrometer.  Cell biological imaging equipment includes a Zeiss Axioplan fluorescence microscope equipped with  CFP/YFG/GFP/Rhodamine filter sets and a Zeiss MRM Digital camera, a Zeiss confocal microscope and a digital camera, and transmission and scanning electron microscopes. Additional major equipment includes several scintillation counters, multiple preparative ultracentrifuges, a fermenter, environmental chambers, multiple cold rooms, and a photographic darkroom equipped with an XOMAT film developer. There are multiple computers throughout the building available in the graduate computer room and in faculty member laboratories.

 

MOLECULAR BIOPHYSICS

The department of Chemistry and Molecular Biology and Biochemistry offer an interdepartmental certificate program in molecular biophysics supported by a training grant from the National Institutes of Health. This program is designed to prepare students for research and careers that combine interests in the physical and life sciences. Interested students are encouraged to consult David Beveridge in the Chemistry Department or Ishita Mukerji in the MB&B Department.

 

 

MB&B500 Graduate Pedagogy

Identical with: BIOL500

Credit: 0.50

Fall 2005

 

 MB&B501/502 Individual Tutorial, Graduate

Credit: 1.00

 

 MB&B504 Selected Topics in Modern Biology

A seminar primarily concerned with papers taken from current research publications designed for, and required of, graduate students;  one 90-minute meeting each week.

Credit: 0.25

 

 MB&B505 Mechanisms of DNA Damage/Repair and Related Diseases

Identical with: MB&B305

Credit: 1.00

Spring 2006

 

 MB&B507 Molecular Biophysics Journal Club I

Identical with: CHEM307

Credit: 0.50

Fall 2005

 

 MB&B508 Molecular Biophysics Journal Club II

Identical with: CHEM308

Credit: 0.50

Spring 2006

 

 MB&B510 Selected Topics in Molecular Genetics

This is a half semester course.  It will be offered in the second half of the semester.  This is an intensive course consisting of lectures and discussions of selected topics in molecular biology and genetics.  Topics will vary from year to year.

Credit: 0.50

 

 MB&B511 Group Tutorial, Graduate

Credit: 0.25

 

 MB&B512 Molecular, Proteomic and Cell Biological Analysis of Telomere Composition and Function

This course will focus on a critical feature of the eukaryotic cell known as the telomere, or linear chromosome end.  We will discuss the diverse set of critical molecular mechanisms affected by and involving telomeres including chromosome segregation, cellular aging, meiotic gamete production, and cancer progression. We will also focus on the physical architecture of the telomere, how this architecture dynamically alters in different biological contexts, and the types of molecules known to associate with telomeres in multiple model organisms including yeast and human cells.  An emphasis will be placed on experimental strategies used for identifying new components of the telomere complex and for understanding telomere function during normal and diseased cellular states.

Credit: 0.50

Fall 2005

 

 MB&B516 Topics in DNA Replication

The rapid accumulation of knowledge concerning DNA replication embraces biochemical, genetic, and physiological aspects of such replication, as well as their implications for determining the structure and function of DNA. This one-half semester course will deal with current aspects of DNA replication with a strong biochemical emphasis on its enzymology. Topics will include DNA precursors and their control, initiation and the function of initiation proteins, individual replication enzymes and the enzymology of the replication fork, termination of replication, and regulation of replication.

Credit: 0.50

 

 MB&B519 Structural Mechanisms of Protein-Nucleic Acid Interactions

Identical with: CHEM519

Credit: 0.50

 

 MB&B520 Topics in Nucleic Acid Structure

This course focuses on the principles of nucleic acid structure. The scope of this course is to go beyond the common DNA structures such as B-DNA and A-DNA helical structures.  The course will concentrate on other DNA structural motifs like branched DNA, supercoiled DNA, triplex DNA and quadruplex DNA. Physical characterization of these structures as well as the functional implication of these structures (in terms of DNA replication, transcription, telomeres, etc.) will be discussed extensively. Discussion will also center on the forces that stabilize these structures, such as H-bonding and stacking interactions. The course will also cover other important DNA structural motifs such as curved or bent DNA as found in A-tracts and the relevance of these structures in promoter recognition and gene expression. Important RNA structures, such as ribozymes and pseudoknots will also be discussed. We will also discuss the significance of DNA structural motifs in eukaryotic genomes and the application of bioinformatic tools to search for these motifs.

Credit: 0.50

 

 MB&B521 Aspects of the Biochemistry of Cancer

This course will discuss some of the classical and current observations concerning alterations in biochemical metabolic pathways that occur upon cellular transformation.  The mechanism of action of various mitogens such as growth factors and phorbal esters and their effects on protein phosphorylations, changes in membrane components and alterations in carbohydrate metabolism are among the topics.

Credit: 1.00

 

 MB&B522 Mechanisms of Protein Trafficking within Cells

This is a half-semester course.  It will be offered the first half of the semester.   This course surveys mechanisms of membrane protein topogenesis and protein secretion starting with E. Coli and progressing to eucaryotic cells.

Credit: 0.50

 

 MB&B523 Energetics and Mechanisms of Protein-Nucleic Acids Interactions

Identical with: CHEM523

Credit: 1.00

 

 MB&B525 Energetics of Protein-Nucleic Acid Interactions

Identical with: CHEM525

Credit: 0.50

 

 MB&B527 Topics in Chromatin Structure

This course will investigate the structure of the eukaryotic chromosome and consider how that structure influences fundamental biological processes such as recombination, DNA replication, chromosome segregation and gene expression.  We will also examine the elements necessary for maintaining and propagating chromosomes, including telomeres, centromeres, and replication origins.  We will use primary sources from scientific literature and a discussion format to appreciate current approaches, conclusions, and unresolved issues in the field.     This is a half semester course.  It will be taught the first half of the semester.

Credit: 0.50

 

 MB&B528 Topics in Eukaryotic Genetics: Transcription

This half semester course will follow two principle themes: we will examine the use of genetic methods in current biological research, and apply these methods to address questions about the regulation of gene expression in eukaryotes.  Our examination of transcriptional regulation will lead us into the related topics of gene organization, chromosome structure, and signal transduction.

Credit: 0.50

Fall 2005

 

 MB&B529 Advanced Microbiology

This course will deal with new exciting concepts in microbiology that can not be considered in an undergraduate course.  Topics will include the Biosphere, space, (exomicro-biology) environmental topics involving pollution, Biolfilms, and microbes as geological agents, industrial microbiology, new concepts in pathogenicity of microbes and viruses, and evolution.

Credit: 0.50

 

 MB&B530 Molecular and Cellular Basis of Human Diseases

This course shall cover the molecular, genetic, cellular and biochemical aspects of selected human ailments.  Topics will include aging, atherosclerosis, osteoporosis, diabetes, obesity and Alzheimer's Disease.

Credit: 1.00

Spring 2006

 

 MB&B531 The Genomics of Evolution, Adaptation, and Regulation

Identical with: MB&B331

Credit: 1.00

 

 MB&B532 Structure-Function and Kinetics of DNA Metabolic Enzymes

The key to understanding how enzyme catalysts work is to understand their structure and properties, and the kinetics and thermodynamics of their reactions.  In this course you will learn how the principles of kinetics and thermodynamics are used to investigate the mechanisms of action of these biological machines.  The focus, in particular, will be on learning the workings of enzymes responsible for DNA replication, repair, and recombination.

Credit: 0.50

 

 MB&B533 Gene Regulation

The MBB department is focused on the molecular and biochemical pathways that lead to cellular phenotype.  Integral to our understanding of these pathways is elucidating how biological information is integrated - specifically, how the cell considers all of the various inputs, integrates these signals, and produces predictable cellular outcomes.  This course will be the first offered in the MBB department in which the central theme is how biological information is integrated.  Specifically, we will focus on the integration that takes place in the cell nucleus.  Here, information about the developmental status of a cell, presented in the nucleus in the form of combinations of transcription factors, is integrated at gene promoters to produce predictable patterns of gene expression.  We will cover three important and emerging topics in gene regulation: 1) how promoters function as integrated circuits, 2) how the histone (i.e., epigenetic) code may compensate for a curiously low level of apparent genetic instruction as to which transcription factors should bind to which promoters, and 3) how microarray technology leads to a whole-systems view of gene co-regulation.  These topics in gene regulation are an emerging focal point in the Human Genome Project.

Credit: 0.50

 

 MB&B537 Molecular Basis of Pathogenicity

This course will focus on a variety of new concepts concerning the molecular and genetic basis of pathogenicity emphasizing organisms that may be used for Bioterrorism as well as others that have played an important role in human illnesses.  Bacteria and viruses will be covered.

Credit: 1.00

 

 MB&B539 Gene Regulation

This is a 1/2 semester course (Tuesday, September 13, thru Tuesday October 25).   Discussion of topics in the regulation of eukaryotic gene expression such as: Transcription factors and their mode of action; enhancers; silencers; locus control region and insulators; and the role of nucleosome positioning and chromatin structure.  In addition, several illuminating systems such as the response to steroid hormones or heat shock; the control of yeast mating type; muscle differentiation and MyoD; and homeoproteins in development will be examined.  Control of gene expression by RNA processing, stability or translation will be briefly considered.  Emphasis throughout the course will be placed on the experimental methods that have given us our current understanding of the regulation of gene expression.

Credit: 0.50

 

 MB&B544 Gene Expression: The Translation Step and Its Control

This course will cover problems of current research interest in molecular biology with special emphasis on the synthesis, structure, and functions of RNA; the synthesis of proteins; the control of post-transcriptional genetic activities; and the transfer of genetic information.  These topics are discussed as they may relate to the mechanisms underlying hormonal regulation, embryonic development and cellular differentiation.

Credit: 0.50

 

 MB&B550 Bioinformatics and Functional Genomics

Identical with: BIOL350

Credit: 1.00

 

 

 MB&B557 Research Seminars in Molecular Biology

Weekly informal presentations by graduate students about their research projects.  This includes description of experimental outline, technical details, problems that are encountered and possible solutions.  The active informal discussion among the participants is designed to generate communication skills, new ideas, interpretations and introduce novel techniques that would aid the graduate student.  There will also be formal seminars of more advanced research projects intended as an exercise in public speaking and a comprehensive presentation.  A summary of the work accomplished during the practicum (MB&B 501, 502) will be expected of first year students.  A sixty minute meeting every week is planned.  (This course is required of all graduate students).

Credit: 0.25

Fall 2005

 

 MB&B558 Research Seminars in Molecular Biology

Weekly formal presentations by graduate students about their research projects.  This includes description of experimental outline, technical details, problems that are encountered and possible solutions.  The active discussion among the participants is designed to generate communication skills, new ideas, interpretations and introduce novel techniques that will aid the graduate student.  There will also be formal seminars on more advanced research projects intended as an exercise in public speaking and a comprehensive presentation.  A summary of the work accomplished during a practicum will be expected of first year students.  A 60-minute meeting every week is planned.  (This course is required of all graduate students.)

Credit: 0.25

Spring 2006

 

 MB&B570 Multi-Dimensional Nuclear Magnetic Resonance Spectroscopy

Identical with: CHEM570

Credit: 0.50

 

 MB&B575 The Cell-Division Cycle and Cancer

This course will cover a broad range of topics that are related to the process of cell division.  We will discuss how the cell cycle is executed and regulated in a variety of eukaryotic systems.  Major consideration will be applied to discussions of cancer and the defects in cell-division regulation that underlie this disease.  Some of the topics include: growth factors, signaling pathways, apoptosis, cyclin-dependent kinases as cell-cycle regulators, transcriptional and post-transcriptional control of cell cycle genes, DNA replication, DNA damage checkpoints, and tumor suppressors.

Credit: 0.50

 

 MB&B581 Physical Chemistry for Life Scientists

Identical with: MB&B381

Credit: 1.00

 

 MB&B585 Seminar in Molecular Biology

This course includes the presentation and discussion of recent findings in the field of molecular biology.

Credit: 0.25

Fall 2005

 

 MB&B586 Seminar in Molecular Biology

This course includes the presentation and discussion of recent findings in the field of molecular biology.

Credit: 0.25

Spring 2006

 

 MB&B587 Seminar in Biological Chemistry

Identical with: CHEM587

Credit: 0.25

Fall 2005

 

 MB&B588 Seminar in Biological Chemistry

Identical with: CHEM588

Credit: 0.25

Spring 2006

 

 MB&B589 Advanced Research for BA/MA Students

Intensive investigation of special research problems leading to a BA/MA thesis.

Credit: 1.50

 

MB&B591/592 Advanced Research Graduate

Credit: 1.00