Molecular Biophysics and Biochemistry

301 Josiah Willard Gibbs Laboratories, 432.5662
M.S., M.Phil., Ph.D.

Chair
Thomas Steitz

Director of Graduate Studies
Nigel Grindley (301 JWG, 432.5662, mbb.grad@yale.edu)

Professors
Donald Crothers (Chemistry), Jennifer Doudna, Donald Engelman, Joseph Fruton (Emeritus), Alan Garen, Sankar Ghosh (Immunobiology), Nigel Grindley, Andrew Hamilton (Chemistry), Mark Hochstrasser, William Konigsberg, Peter Lengyel (Emeritus), Richard Lifton (Genetics/Internal Medicine/Nephrology), Robert Macnab, I. George Miller (Pediatric Infectious Diseases), Simon Mochrie (Physics; Applied Physics), Peter Moore (Chemistry), Charles Radding (Genetics), Lynne Regan, Frederic Richards (Emeritus), Gaston Schmir (Emeritus), Robert Shulman, Sofia Simmonds (Emeritus), Michael Snyder (Molecular, Cellular, & Developmental Biology), Dieter Söll, Joan Steitz, Thomas Steitz, Scott Strobel, Julian Sturtevant (Emeritus), William Summers (Therapeutic Radiology), David Ward (Genetics), Kenneth Williams (Adjunct, Research), Harold Wyckoff (Emeritus)

Associate Professors
Mark Gerstein, Michael Koelle, Mark Solomon, Sandra Wolin (Cell Biology)

Assistant Professors
João Cabral, Enrique De La Cruz, Lise Heginbotham, Anthony Koleske, Andrew Miranker, Vinzenz Unger

Fields of Study
The principal objective of members of the department is to understand living systems at the molecular level. Areas of current interest include structure and function of biological macromolecules as determined by amino acid or nucleotide sequencing, diffraction, spectroscopic or computational analyses; mechanisms of enzyme action; bioenergetics, motility, and chemotaxis; structure and function of membranes, viruses, ribosomes, ribogymes, nucleosomes, ribonucleoprotein particles, and other macromolecular assemblies; developmental genetics; animal virology; plant molecular genetics; metabolic regulation; protein degradation; DNA transposition replication, recombination, and repair; regulation of RNA and protein synthesis; cell cycle; molecular immunology; chromosome segregation; nuclear organization.

Special Admissions Requirements
Courses in introductory biology, general chemistry, organic chemistry, physical chemistry, mathematics through differential equations, and one year of physics with calculus are required for admission. Biochemistry is recommended. Applicants must take the GRE General Test, which is preferred, or the MCAT.

To enter the Ph.D. program, students apply to an interest-based track within the interdepartmental graduate program in the Biological and Biomedical Sciences.

Special Requirements for the Ph.D. Degree
All first-year students (except M.D./Ph.D.) take three laboratory rotations (MB&B 650a and 651b, Lab Rotation for First-Year Students). All students are required to take, for credit, seven one-term science courses. To obtain the desired breadth and depth of education, students are strongly encouraged to take (or to have taken the equivalent of) the core graduate courses offered by the department in biochemistry, molecular genetics, and structural biology. Additional courses, chosen from within MB&B or from related graduate programs, should form a coherent background for the general area in which the student expects to do dissertation research. All students attend the two departmental seminars: MB&B 675, Seminar for First-Year Students, and MB&B 676b, Responsible Conduct of Research. Students with an extensive background in biochemistry or biophysics are permitted to substitute advanced courses for the introductory courses. There is no foreign language requirement. The student's research committee (see below) makes the final decision concerning the number and selection of courses required of each student. All students are required to teach two terms during their graduate careers, usually during the second and third years. The student selects a research adviser, usually from the department faculty, by the end of the second term of residence. At that time two additional faculty members are chosen to form a research committee. Requirements for admission to candidacy, which usually takes place after four terms of residence, are: (1) completion of course requirements; (2) completion of the qualifying examination; (3) certification of the student's research abilities by vote of the faculty upon recommendation from the student's research committee; and (4) submission of a brief prospectus of the proposed thesis research. The qualifying examination, taken in the fall of the second year, is an oral defense of two short, written research proposals, one in the same area as the student's thesis research and one in a different area; the three-member oral committee includes at least one of the two members of the research committee excluding the thesis adviser, and the remaining one or two members are selected by the Qualifying Examination Committee. Once final drafts of the thesis chapters have been approved by the research committee, the student presents a dissertation seminar to the entire department, only after which may the thesis be submitted. Students must have written at least one first-author paper that is submitted, in press, or published by the time of the thesis seminar.

Honors Requirement
Students must meet the Graduate School's Honors requirement by the end of the fourth term of full-time study.

Master's Degree
M.Phil. See Graduate School requirements. Awarded only to students admitted to candidacy who are continuing for the Ph.D. Students are not admitted for this degree.

M.S. May be awarded to a student who is in good standing upon completion of at least two terms of graduate study (granted to students who are not continuing in the Ph.D. program). Note that a High Pass average is required for obtaining a master's degree.

M.S. (for industrial affiliates). Scientists working in industry may attend courses and conduct research projects leading to the M.S. degree. Information may be obtained from the director of graduate studies.

Program materials are available upon request to the Director of Admissions, Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven CT 06520-8114.

Courses
MB&B 600au, Principles of Biochemistry I. Michael Koelle, Donald Engelman. Tues/Thurs 11.30-12.45
Rigorous introduction to the major concepts of biochemistry and to the process of discovery in this discipline, with emphasis on macromolecular conformation, physical processes in biochemistry, and carbohydrate, lipid, and amino acid metabolism.

MB&B 601bu, Principles of Biochemistry II. Scott Strobel, Joan Steitz. Tues/Thurs 11.30-12.45
The chemistry and metabolism of nucleic acids, the mechanism and regulation of protein and nucleic acid synthesis, and selected topics in macromolecular biochemistry.

MB&B 625au, Basic Concepts of Genetic Analysis. Tian Xu, Michael Koelle, Richard Lifton, Shirleen Roeder, Michael Stern. Tues/Thurs 1.05-2.20
The universal principles of genetic analysis in eukaryotes are discussed in lectures. Students also read a small selection of primary papers illustrating the very best of genetic analysis and dissect them in detail in the discussion sections. While other Yale graduate molecular genetics courses emphasize molecular biology, this course focuses on the concepts and logic underlying modern genetic analysis. A brief review of undergraduate genetics is offered in two optional lectures at the beginning of the term. Also GENE 625a, MCDB 625au.

MB&B 642a, Roles of Microorganisms in the Living World. L. Nicholas Ornston, Diane McMahon-Pratt, Robert Macnab. Tues/Thurs 11.30-12.45

MB&B 650a and 651b, Lab Rotation for First-Year Students. Nigel Grindley.
Required for all first-year graduate students.

MB&B 658a, Research Topics in Biophysics. Donald Crothers. Tues/Thurs 2-3.30
An advanced treatment of the fundamental physical properties that dictate the behavior of biological molecules. Taught with participation of a number of biophysics faculty and extends to their current research specialties. Also CHEM 558a.

MB&B 675, Seminar for First-Year Students. Michael Koelle, Andrew Miranker, and staff. Friday 4
Required for all first-year graduate students.

MB&B 676b, Responsible Conduct of Research. Mark Solomon or Lynne Regan and staff. Friday 4
Designed for students who are beginning to do scientific research. The course seeks to describe some of the basic features of life in contemporary research and some of the personal and professional issues that researchers encounter in their work. Approximately six sessions during the spring term, run in a seminar/discussion format. Required for all first-year graduate students. Also CBIO 676b.

MB&B 700bu, Properties of Macromolecules. Lynne Regan, Vinzenz Unger, Mark Gerstein. Mon/Wed 11.30-12.45
Solution properties of macromolecules and current topics in biophysics, including electrostatics, hydrodynamics, enzyme kinetics, molecular dynamics, and multiple equilibria. Prerequisites: physical chemistry; biochemistry.

MB&B 701b3u, Diffraction Methods. João Cabral, Jennifer Doudna, Vinzenz Unger. Tues/Thurs 9-10.15
Biological applications of X-ray crystallography, small-angle X-ray, and neutron scattering and cryoelectron microscopy.

MB&B 701b4u, NMR Methods. Andrew Miranker. Tues/Thurs 9-10.15
Basic principles of NMR with emphasis on biological applications in the primary literature. Application areas include structure determination, drug binding, molecular recognition, protein folding, and in vivo metabolism. Prerequisites : physical chemistry and biochemistry.

[MB&B 704au, Structural Biology.]

MB&B 705au, Molecular Genetics of Prokaryotes. Nigel Grindley, Charles Radding, Joann Sweasy. Mon/Wed 11.30-12.45 Molecular aspects of the storage, replication, evolution, and expression of genetic material in prokaryotes. Required: previous or concurrent introductory courses in genetics and biochemistry. Also GENE 705a, MCDB 505au.

MB&B 710b4, Electron Cryo-Microscopy for Protein Structure Determination. Vinzenz Unger, Fred Sigworth.
Understanding cellular function requires structural and biochemical studies at an ever-increasing level of complexity. The course is an introduction into the concepts and applications of high-resolution electron cryo-microscopy. This rapidly emerging, new technique is the only tool known to date that allows biological macromolecules to be studied at all levels of resolution ranging from their cellular organization to near atomic detail. Also C&MP 710b.

MB&B 741au, Structure and Chemistry of Proteins and Nucleic Acids. Jennifer Doudna, Thomas Steitz. Tues/Thurs 11.30-12.45
Selected topics in the structure of proteins and nucleic acids; sequence dependent interactions between proteins and nucleic acids; chemical modifications of DNA; chemical studies of DNA-binding proteins; catalytic RNA. Prerequisite: biochemistry.

MB&B 743bu, Molecular Genetics of Eukaryotes. Mark Hochstrasser, Anthony Koleske. Tues/Thurs 11.30-12.45
Selected topics in regulation of gene expression, genome structure and evolution, signal transduction, cellular physiology, development, and carcinogenesis. Prerequisite: biochemistry or permission of the instructor. Also GENE 743b.

[MB&B 746a1, Advanced Biochemical Control.]

MB&B 749au, Medical Impact of Basic Science. Joan Steitz, Mark Hochstrasser, Andrew Miranker, and staff. Tues/Thurs 1-2.30
Consideration of examples of recent discoveries in basic science that have elucidated the molecular origins of disease or that have suggested new therapies for disease. Emphasis is placed on the fundamental principles on which these advances rely. Reading is from the primary scientific and medical literature, with emphasis on developing the ability to read this literature critically. AIMED at seniors and first-year graduate students. Prerequisite: MB&B 600au/601bu or the equivalent or permission of the instructor. Also GENE 749a.

MB&B 750a2, Biological Membranes. Vinzenz Unger (in charge), João Cabral, Donald Engelman, Lise Heginbotham. Mon/Wed 10-11.15
Biological membranes and their resident proteins are essential for cellular function; yet comparatively little is known about their structure and dynamics. This module serves as a brief introduction to the biochemistry and biophysics of lipids, lipid bilayers, and lipid-derived second messengers. In addition, structural as well as functional aspects of the different classes of membrane proteins are discussed along with an outline of experimental approaches used to achieve an understanding of membrane protein structure and function at a molecular level.

MB&B 752au, Genomics and Bioinformatics. Dieter Söll, Mark Gerstein, Michael Snyder. Mon/Wed 1-2.15
Genomics describes the determination of the nucleotide sequence and many further analyses to discover functional and structural information on all the genes of an organism. Topics include the methods and results of functional and structural gene analysis on a genome-wide scale as well as a discussion of the implications of this research. Bioinformatics describes the computational analysis of genomes and macromolecular structures on a large scale. Topics include sequence alignment, biological database design, comparative genomics, geometric analysis of protein structure, and macromolecular simulation. Prerequisite: EEB 122b and MATH 115, or permission of the instructor. Also MCDB 752au.

[MB&B 760b4u, Principles of Macromolecular Crystallography.]

MB&B 775b, Advanced Seminar in Genetics

MB&B 800a, Molecular Mechanisms of Disease. Robert Shulman, William Konigsberg, Andrew Miranker, Dieter Söll.
The course describes selected medical applications of recent findings in the biochemical properties of biomolecules and their interactions.

MB&B 900a or 901b, Reading Course in Biophysics.
Directed reading course in biophysics. Term paper required. By arrangement with faculty.

MB&B 902a or 903b, Reading Course in Molecular Genetics.
Directed reading course in molecular genetics. Term paper required. By arrangement with faculty.

MB&B 904a or 905b, Reading Course in Biochemistry.
Directed reading course in biochemistry. Term paper required. By arrangement with faculty.

The following courses are for students in the joint B.S./M.S. program with Yale College:

MB&B 569b or MB&B 572b, Independent Research for B.S./M.S. Candidates. Scott Strobel.

MB&B 570a or MB&B 571b, Intensive Research Seminar for B.S./M.S. Candidates. Scott Strobel, Nigel Grindley.

Next: Molecular, Cellular, and Developmental Biology