2000-01 Bulletin Entry for:


Biochemistry


Objectives


Undergraduate Concentration

The biochemistry major is designed to equip students with a broad understanding of the chemical and molecular events involved in biological processes. The biochemistry concentration provides a foundation for careers in medicine, biotechnology, or research in all branches of the biological sciences.

Graduate Program in Biochemistry

The graduate program in biochemistry leading to the degree of Doctor of Philosophy is designed to provide students with a deep understanding of the chemical principles governing the workings of biological macromolecules. The bioorganic chemistry track of this program gives students the option of training in organic chemistry in addition to biochemistry. The emphasis in the graduate program is placed upon experimental research work to train students to carry out independent original research. However, students are required to complete formal course work in advanced biochemistry, molecular biology, and physical biochemistry. Students in the bioorganic chemistry track supplement this core curriculum with courses in organic synthesis and other topics in organic chemistry. Additional courses and seminars are available in a wide range of subjects, including enzyme regulation and mechanism, neurobiology, immunology, structural biochemistry, membrane biology, and molecular genetics. Students are encouraged to choose advanced courses and seminars according to their particular interests. Doctoral research topics are chosen in areas under investigation by the faculty; these include problems in macromolecular structure and function, enzyme function and regulation, RNA processing, gene regulation, membrane transport and receptor function, molecular pharmacology, mechanisms of cell motility, microbial metabolism, and the biochemistry of cellular electrical excitability. A theme running through this research is the relationship of biochemical functions to underlying molecular structures and mechanisms.

The graduate program in biochemistry leading to the degree of Master of Science is designed to give students a substantial understanding of the chemical and molecular events in biological processes and experience in research. The program is divided among formal course work, biochemical techniques, and a research project. Additional courses and seminars are available in a wide range of subjects, as described above.


How to Become an Undergraduate Concentrator


The general aim of the concentration is to ensure that the students first learn the necessary chemical and physical chemical background and then the basic principles and observations of biochemistry and molecular biology. The department also offers a variety of introductory and advanced courses in more specialized subjects such as neurobiology, X-ray crystallography, and physical biochemistry. These courses sample the range of subjects that can be studied by biochemical methods and from a biochemical point of view.


How to Be Admitted to the Graduate Program


The general requirements for admission to the Graduate School, given in an earlier section of the Bulletin, apply here. Applicants for admission to the biochemistry Ph.D. program are also required to take the Graduate Record Examination. It is strongly suggested that the applicant take one of the advanced sections of this examination. The applicant's undergraduate curriculum should include fundamental courses in biology and chemistry.


Faculty


Daniel Oprian, Chair

Structure-function studies of visual pigments and other cell surface receptors.

Jeff Gelles

Mechanisms of mechanoenzymes. Stochastic processes in single enzyme molecules. Light microscopy as a tool to study enzyme mechanisms.

Nikolaus Grigorieff

High resolution electron cryo-microscopy of membrane proteins and channels.

Lizbeth Hedstrom

Enzyme structure-function studies. Protein engineering. Design of enzyme inhibitors.

Dorothee Kern

Dynamics of enzymes. Magnetic resonance methods.

John Lowenstein

Role of phospholipids in hormone action. Regulation of lipogenesis. Regulation and function of the purine nucleotide cycle. Regulation and function of adenosine production in the heart. Techniques of cloning and high level expression of proteins.

Christopher Miller

Structure and function of ion channel proteins. Membrane transport and mechanisms of electrical excitation.

Melissa Moore

Molecular biology of self-splicing introns and the splicesome. Mechanisms of RNA catalysis.

Gregory Petsko (Director, Rosenstiel Center)

X-ray crystallographic analysis of protein structure and enzyme mechanisms.

Dagmar Ringe (Rosenstiel Center)

Structures of enzymes and enzyme-substrate complexes. X-ray crystallography.


Requirements for the Undergraduate Concentration


Required of all candidates: One year each of general chemistry with laboratory, organic chemistry with laboratory, and physics taught using calculus (PHYS 11) with laboratory (this must be taken before the senior year); a year of physical biochemistry (CHEM 41a and BCHM 104b or CHEM 41b); Introductory Biochemistry (BCHM 100a); Genetics and Molecular Biology (BIBC 22a) with laboratory; Molecular Biology (BIBC 105b). The laboratory associated with CHEM 41 is optional. AP credit or advanced standing awarded by the chemistry department can stand in lieu of general chemistry.

No course offered for concentration requirements may be taken pass/fail. Grades below C- in BCHM and BIBC courses offered for the concentration (and in CHEM 41a and b) cannot be used to fulfill the requirements of the concentration.

A student may graduate with a double concentration in biochemistry and biology, or in biochemistry and chemistry, if the concentration requirements in each department are fully met.

Honors Program

Courses required of all candidates listed above plus one year each of BCHM 101 and 99, submission of an acceptable research thesis, and a grade point average of 3.00 in the sciences and mathematics. BCHM 99 may not exceed three semester course credits. Petition for this program is made at the beginning of the senior year.

Combined B.A./M.S. Program

This program requires completion of 38 courses, including the courses required of all candidates listed above, plus a summer research residency and four one-semester 100-level courses beyond any such courses used to fulfill minimal requirements for the concentration in biochemistry. These additional 100-level courses are approved by the department and would normally include a year of BCHM 101 and one or two semesters of research under BCHM 150. Not less than three nor more than four semesters of research credit total (BCHM 99 plus 150) are required for the research component of the B.A./M.S. Program. A candidate must have a grade point average of 3.00 in the sciences and mathematics, and grades of B- or better are required in the above four 100-level semester courses counted under the graduate portion of the B.A./M.S. Program. Application to this program is made to the department and Graduate School no later than May 1 preceding the senior year, and all work must be completed by the time the B.A. is awarded, including the thesis. A substantial research contribution is required and, if a thesis is found unacceptable under this program, it will automatically be considered under the Honors Program. It is advisable, in order to complete the Honors Program or the combined B.A./M.S. Program, to gain exemption where possible from introductory courses in science and mathematics. This is especially important for the premedical student who must also fulfill requirements imposed by medical schools.


Requirements for the Degree of Master of Science


Program of Study

Students must successfully complete an approved program of at least eight courses. These courses would normally include five graduate-level courses in biochemistry and related areas with the remaining courses being thesis research. The five graduate-level courses would normally include Advanced Biochemistry (BCHM 101a and b) and three of the following four courses: Physical Chemistry of Macromolecules (BCHM 104b); Molecular Biology (BIBC 105b); Biochemical Techniques (BCHM 200a and b). Students who complete the program and thesis with distinction may be invited by the department to continue under the Ph.D. program. Note that the above named courses are also required for the Ph.D. program described below.

Residence Requirement

The minimum residence requirement is one year.

Language Requirement

There is no language requirement.

Thesis

M.S. thesis describing original research carried out in the laboratory of the research advisor.


Requirements for the Degree of Doctor of Philosophy


Program of Study

Students must successfully complete the core curriculum defined below. Biochemistry students will typically complete the core curriculum in the first year.

Core curriculum:

BCHM 101a,b Advanced Biochemistry

BCHM 104b Physical Chemistry of Macromolecules

BIBC 105b Molecular Biology

BCHM 200a,b Biochemical Techniques (Lab rotations)

CONT 300b Ethical Practices in Health-Related Sciences

Students must also successfully complete:

Four other advanced courses (100-level or above) from the Biochemistry, Biology, Biophysics, Chemistry, or Neuroscience Programs. These courses must include at least two courses selected from BCHM 219-250.

Bioorganic Chemistry Track

In order to receive a Ph.D. in biochemistry with a specialization in bioorganic chemistry, students must complete:

A. The core curriculum defined above.

B. Two rotations dealing with problems in organic chemistry a part of BCHM 200a,b.

C. CHEM 134a Advanced Organic Chemistry: Synthesis. (Bioorganic track students have the option of substituting CHEM 134a for either BCHM 104b or BIBC 105b in the first year and completing the core curriculum in the second year.)

D. Two courses selected from BCHM 219-250.

E. One other advanced chemistry courses, chosen from:

CHEM 111a Computational Chemistry

CHEM 130a Advanced Organic Chemistry: Structure

CHEM 131a Advanced Organic Chemistry: Topics in Structure and Reactivity

CHEM 132b Advanced Organic Chemistry: Spectroscopy

CHEM 137b The Chemistry of Organic Natural Products

CHEM 229b Introduction to X-ray Structure Determination

CHEM 235b Advanced NMR Spectroscopy

Residence Requirement

The minimum residence requirement is three years.

Language Requirements

There is no foreign language requirement.

Financial Support

Students may receive financial support (tuition and stipend) throughout their participation in the Ph.D. program. This support is provided by a combination of University funds, training grants, and individual research grants.

Teaching

As a part of the graduate training program, Ph.D. students are required to participate as teaching assistants for two terms.

Qualifying Examinations

An oral qualifying examination must be taken generally at the beginning of the second year. In this examination, the student will be asked to defend or refute two propositions. One proposition will be assigned in an area of research outside the student's immediate area of specialization, and one will be an original proposition put forth by the student for a research problem in his or her area of interest (this is not necessarily a problem upon which he or she will carry out research).

In addition, the student must successfully pass a comprehensive examination administered at the end of the second year of study.

Dissertation and Defense

A dissertation will be required that summarizes the results of an original investigation of an approved subject and demonstrates the competence of the candidate in independent research. This dissertation will be presented in a departmental lecture and defended in a Final Oral Examination.


Courses of Instruction



(1-99) Primarily for Undergraduate Students


BIBC 22a Genetics and Molecular Biology

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Prerequisites: CHEM 10a,b or 11a,b or 15a,b. CHEM 25a and BIOL 18a must be taken before or concurrently with this course.

An introduction to the current understanding of hereditary mechanisms and the cellular and molecular basis of gene transmission and expression. Usually offered every year.

Messrs. Fulton and Wensink

BCHM 98a Readings in Biochemistry

Prerequisites: BIBC 22a; BCHM 100a or 102a; and one year of organic chemistry with laboratory. Enrollment limited. Signatures of the concentration advisor and mentor required. Does NOT satisfy the concentration requirement in biochemistry.

Directed scholarship on selected topics in biochemistry for outstanding juniors or seniors. Regularly scheduled discussion and written assignments leading to a substantive term paper. The tutorial is arranged only by mutual agreement between a faculty mentor and student. Usually offered every year.

Staff

BCHM 99a Research for Undergraduates

Prerequisites: BIBC 22a; and BCHM 100a; one year of organic chemistry with laboratory. Requirement of BCHM 100a may be waived. Enrollment limited. Signature of department chair required.

Undergraduate research. A maximum of three course credits may be taken as BCHM 99a and/or 99b. At the discretion of the department, one semester may be taken for double credit (99e). Offered every year.

Staff

BCHM 99b Research for Undergraduates

See BCHM 99a for special notes and course description. Offered every year.

Staff

BCHM 99e Research for Undergraduates

See BCHM 99a for special notes and course description. Offered every year.

Staff


(100-199) For Both Undergraduate and Graduate Students


BCHM 100a Introductory Biochemistry

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Prerequisite: One year of organic chemistry with laboratory. Enrollment limited to 70.

Topics include chemistry, reaction, and metabolism of biologically important compounds; formation and utilization of "energy-rich" compounds; introduction to enzyme mechanisms; interrelation and comparison of basic biochemical and chemical processes; and metabolic regulation. Usually offered every year. Multiple sections.

Mr. Lowenstein (fall), Mr. Grigorieff (spring)

BCHM 101a Advanced Biochemistry I

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Prerequisites: One year of organic chemistry with laboratory and

BCHM 100a or their equivalent. Enrollment limited to 50.

A discussion of enzyme reactions, including energetics, kinetics, and reaction mechanisms. Metabolism of carbohydrates, lipids, amino acids, nucleic acids, vitamins and coenzymes, and hormones and inorganic substances. Coupled enzyme reactions and the synthesis of macromolecules. Regulated enzymes and the regulation of metabolism. Usually offered every year.

Ms. Kern (fall)

BCHM 101b Advanced Biochemistry II

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Prerequisite: BCHM 101a or permission of instructor. Enrollment limited to 50.

Chemical logic of metabolic pathways. Structural function of membrane proteins, ion channels, and signal transduction. Usually offered every year.

Mr. Oprian (spring)

BCHM 104b Physical Chemistry of Macromolecules

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Prerequisite: CHEM 41a (Physical Chemistry, Lectures I) and either BCHM 100a or BCHM 101a.

The course illustrates principles by which biological macromolecules behave in aqueous solution. Topics include linkage between ligand binding and conformations changes, protein folding, protein-DNA recognition, hydrophobic forces, single-molecule behavior. Protein, nucleic acid, and membrane structural principles will also be disussed. Offered every year.

Messrs. Gelles and Miller

BIBC 105b Molecular Biology

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Prerequisites: BIBC 22a and BIOL 22b.

Examination of molecular processes in replication and expression of genetic information and techniques by which this understanding has been achieved. Topics include recombinant DNA and other molecular biological techniques, structure and organization of DNA in chromosomes, DNA replication, transcription and regulation of gene expression, RNA structure and processing, mRNA stability, and other mechanisms of post-translational control. Usually offered every year.

Messrs. Rosbash and Sen

BCHM 128b Statistical Biophysics and Biochemistry

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Prerequisite: One year of college chemistry and one year of calculus or permission of the instructor.

Biochemists and molecular biophysicists seek to understand the behavior of living systems in terms of the properties of individual molecules. Because molecular motions are random, molecular properties are often best thought of in statistical terms. This course will give an introduction to the tools of probability theory and molecular statistics. We will then apply these tools to a variety of interesting biological problems, including: molecular diffusion, binding of ligands to cell surface receptors, bacterial chemotaxis, single-channel kinetics, and biochemical separation methods. Usually offered every fourth year. Will be offered in the spring of 2001.

Messrs. Gelles and Miller

BCHM 150a Research for B.A./M.S. Candidates

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Prerequisites: BIBC 22a and BCHM 100a; one year of organic chemistry and laboratory; BCHM 99d. Enrollment limited and signature of department chair required.

The final semester(s) of laboratory research under the B.A./M.S. Program, to be pursued under the supervision of a faculty advisor. Usually offered every year.

Mr. Lowenstein and Staff

BCHM 150b Research for the B.A./M.S. Candidates

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See BCHM 150a for special notes and course description. Usually offered every year.

Mr. Lowenstein and Staff

BCHM 151b Ion Channel Proteins

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This course considers the molecular properties of ion channels, the most basic element of molecular hardware in the nervous system. We examine the molecular architecture of channels and the mechanisms of channel activity. The mechanisms of voltage-dependence, ion selectivity, and channel gating will be emphasized. Usually offered in odd years.

Mr. Miller

BCHM 171b Protein X-ray Crystallography

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Prerequisites: Familiarity with computing is necessary and a basic biochemistry course is recommended.

A practical guide to the determination of three dimensional structures of proteins and nucleic acids by X-ray diffraction. Students will learn theory behind diffraction from macromolecular crystals and will carry out all of the calculations necessary to solve a protein structure at high resolution. Usually offered in even years.

Mr. Petsko and Ms. Ringe


(200 and above) Primarily for Graduate Students


BCHM 200a and b Biochemistry Techniques

Prerequisite: BCHM 101. May be taken concurrently.

Usually offered every year.

Mr. Gelles and Staff


Advanced Topic Courses

Topics are repeated usually at two- to three-year intervals.

BCHM 219b Enzyme Mechanisms

Ms. Kern

BCHM 220a Proteases

Ms. Hedstrom

BCHM 222a Protein Kinases and Phosphatases

Mr. Lowenstein

BCHM 223a Membrane Proteins

Messrs. Miller and Oprian

BCHM 224a Microtubule-Based Mechanoenzymes

Mr. Gelles

BIBC 224b The RNA World

Prerequisites: BCHM 100a, BIBC 105b, or permission of the instructor.

This course employs seminars and lectures to approach a wide range of topics in RNA research. Topics include RNA enzymes, RNA structure, protein-RNA interactions, pre-MRNA splicing, and RNA localization. Usually offered every year.

Ms. Moore


Graduate Research

BCHM 401d Biochemical Research Problems

Independent research for the M.S. and Ph.D. degrees. Specific sections for individual faculty members as requested.

Staff


Journal Club, Colloquia, and Research Clubs

In addition to the formal courses announced above, all graduate students are expected to participate in the department's Research Clubs and Colloquia. Colloquia are general meetings of the department in which department and guest speakers present their current investigations. Research clubs are organized by various research groups of the department.


CONT 300b Ethical Practice in Health-Related Sciences

Required of all first-year graduate students in health-related science programs. Not for credit.

Scientists are becoming increasingly aware of the importance of addressing ethical issues and values associated with scientific research. This course, taught by University faculty from several graduate disciplines, will cover major ethical issues germane to the broader scientific enterprise, including areas or applications from a number of fields of study. Lectures and relevant case studies will be complemented by two public lectures during the course. Usually offered every year.

Staff


Cross-Listed Courses


CHEM 235b

Advanced NMR Spectroscopy