Department of Biochemistry and Biophysics

www.med.unc.edu/biochem

LESLIE V. PARISE, Chair

Professors

Sharon Campbell (18) NMR Spectroscopy, Structure and Regulation of Proteins Involved in Ras-Mediated Cell Signaling

Charles W. Carter Jr. (19) Structural Molecular Biology, Protein Structure-Function, X-ray Crystallography of Proteins Including Aminoacyl tRNA Synthetases, Deaminases, Phasing Methods and Crystal Growth

David Clemmons (15) Receptor Signaling

Lyndon Cooper (21) Osteoblast Responses to Physiological Stress: Characterization of the Heat Shock Response and Mechanochemical Deformation and Stimulation

Stephen Crews (24) Molecular Genetics of Nervous System Development, Transcriptional Control, Evolution of Regulatory Mechanisms

Henrik Dohlman (17) Regulators of G Protein Signaling, Mechanisms of Drug Desensitization

Nikolay Dokholyan (47) Computational Structural Biology

Marshall Edgell (143) Use of Biophysical and Genetic Techniques Using Combinatorial Libraries and High Throughput Robotics to Assess Determinants of Protein Structure

Beverly Errede (144) Function and Regulation of MAP-Kinase Activation Pathways in Saccharomyces cerevisiae

Jack Griffith (41) Architecture of DNA-Protein Complexes Involved in Replication, Repair, and Telomere Maintenance; Electron Microscopy

David G. Kaufman (53) Cellular and Molecular Mechanisms of Cancer Development, Epithelial Cell-Stromal Cell Interactions, Cell-Cycle Influences on Carcinogenesis

Hengming Ke (50) X-ray Crystallography, Structure and Function of Biologically Important Proteins such as Phosphodiesterase and Molecular Chaperone System

Brian Kuhlman (72) Computational Protein Design, Protein-Protein Interactions, Structural Biology

Barry R. Lentz (62) Biomembrane Structure and Its Relationship to Function, Platelet Membranes in Blood Coagulation, Membrane Fusion, Liposomes

Patricia F. Maness (68) Mechanisms of Cell Signaling and Adhesion, Axon Guidance and Synaptic Plasticity

William F. Marzluff (69) Control of Gene Activity, Cell-Cycle Regulation in Early Embryos, Control of Expression of Histone mRNA

Gerhard W. Meissner (79) Intracellular Ca2+ Signaling and Regulation of Ion Channels in Striated Muscle

Gary Pielak (99) Protein Structure/Function Using 2-D NMR

Dale Ramsden (108) Mechanism of V(D)J Recombination, End-Joining Pathway for Repair of DNA Double Strand Breaks

Matthew Redinbo (110) Structural Biology of Proteins and Protein-Nucleic Acid Complexes

John Riordan Membrane Protein Structure-Function, ABC Proteins in Human Disease, Ion Channel Function, Cellular Protein Quality Control, Molecular And Cellular Biology of Cystic Fibrosis

Aziz Sancar (105) DNA Repair and Cancer, Structure and Function of DNA Repair Enzymes, Molecular Neurobiology, Reaction Mechanism of Human Blue-Light Photoreceptor

Gwendolyn B. Sancar (104) Cellular Responses to Genotoxic Stress, DNA Repair, Transcriptional Regulation of Stress Response Genes

John Sondek (117) Protein Crystallography and Signal Transduction

Ronald I. Swanstrom (123) Molecular Biology of HIV, Resistance to HIV Protease Inhibitors

Michael D. Topal (126) Protein-DNA Recognition, Genomic Instability

Thomas W. Traut (128) Enzyme Structure and Regulation, Allosteric Dissociating Enzymes

Elizabeth M. Wilson (134) Mechanisms of Steroid Hormone Action, Androgen Regulation of Gene Transcription

Richard V. Wolfenden (139) Enzyme Mechanisms, Water Affinities of Biological Compounds

Yue Xiong (140) Molecular Mechanisms of Cell Cycle Control, Tumor Suppression and Development

Associate Professors

Xian Chen (12) Protein-Protein and Protein-Ligand Interaction, Protein Tertiary Structure, Quaternary Structure of Multi-Protein Complexes, Structure-Function Relationship of Proteins, Functional Proteomics

Ed Collins (23) Use of Biophysical Tools to Study Immunological Problems Focusing on Immune Recognition of Cancer

Jean Cook (150) Regulation of DNA Replication in Mammalian Cells

Howard M. Fried (39) Cell and Molecular Biology, Mechanisms of Nuclear-Cytoplasmic Transport, Mechanisms of RNA-Protein Recognition

Andrew Lee (71) Protein, Structure and Dynamics, NMR Spectroscopy

Scott Singleton (116) Bio-Organic and Biophysical Chemical Investigations of the Mechanisms DNA Repair, Directed Evolution of Novel Enzymes, Development of Alternate Strategies for Targeting Drug-Resistant Pathogenic Microorganisms

Brian Strahl (120) Mechanisms of Chromatin-Mediated Gene Transcription

Assistant Professors

Wolfgang Bergmeier, Adhesion Mechanisms of Platelets and Neutrophils

Saskia Neher, Lipase Structure and Function, Membrane Proteins, Molecular Chaperones

Gang Greg Wang, Cancer Epigenetics; Chemical Modifications of Histones

Research Professors

Brenda Temple, Structural Bioinformatics

Arrel D. Toews (125) Neurochemistry, Neurotoxicology: Metabolism and Gene Expression during Demyelination and Remyelination, Molecular Biology of Cholesterol Metabolism and Trafficking

Ashutosh Tripathy, Measurement of Affinity, Stoichiometry, Kinetics and Thermodynamics of Interactions among Macromolecules and Their Cognate Ligands

Professors Emeriti

Michael K. Berkut

Michael Caplow

Stephen G. Chaney

Jan Hermans

David J. Holbrook Jr.

George K. Summer

The Department of Biochemistry and Biophysics is an administrative division of the School of Medicine and a member of The Graduate School. The graduate program offers instruction and research opportunities leading to the Ph.D. degree. Although the department offers the M.S. degree, the graduate program is not designed as a terminal master's curriculum. Applicants are offered admission with the expectation that they will complete their doctorate.

Modern research in biochemistry and biophysics is designed to address mechanism and function; it utilizes the paradigms of molecular biology, but is influenced by chemistry, physics, and genetics. The philosophy of the department and its graduate program is to provide students with broad training in modern approaches to the field and unique opportunities for multidisciplinary training.

Curriculum

Students are admitted to the graduate program through the BBSP portal, complete a minimum of three laboratory rotations, and then join the Department of Biochemistry and Biophysics at the end of their first year. All students in the department are required to complete a seminar in biochemistry (BIOC 701) OR seminar in biophysics (BIOC 704); BIOC 712, which is a grant writing course designed to help prepare students for their comprehensive written examination; and BIOC 715, which is a scientific presentation course. Students are also required to complete nine credit hours in core courses and four credit hours of electives. Further information on course requirements may be found at www.med.unc.edu/biochem/students/degree-requirements. Students in the combined M.D./Ph.D. program are required to complete all course requirements.

The director of graduate studies advises entering students about course selection until the student chooses a research sponsor. Students select research sponsors from the department's primary and joint faculty members following the three laboratory rotations. After a research sponsor has been selected, a dissertation committee is formed to review the student's yearly progress. The examinations required for admission to candidacy for the Ph.D. are administered as a comprehensive oral exam, a comprehensive written exam, and a final oral defense of a dissertation. The comprehensive oral exam (defense of the initial thesis proposal) will stress the dissertation proposal and related areas in an effort to ascertain the student's understanding of the research project that he/she is undertaking. The comprehensive written examination will cover major topics in the areas of biochemistry and biophysics and cell and molecular biology. The most important requirement for the Ph.D. degree is a final oral defense of a dissertation or original research carried out independently by the candidate.

Financial Aid and Admissions

Funds available from the University, the department, and individual research grants provide stipends for students. All applicants are considered for special fellowships and teaching or research assistantships. In recent years students received a stipend of $27,500 plus in-state tuition and fees. Major medical insurance was also provided. Nonresidents with predoctoral fellowships or assistantships are recommended for special tuition rates. Applications are considered from prospective graduate students who present evidence of superior scholarship in biology, chemistry, or biochemistry. The department recommends that students prepare themselves by taking general and organic chemistry, biochemistry, biology, physics, and calculus. It is anticipated that students who have not had these courses will take them, as appropriate, after their arrival. Departmental information may be obtained through the department's Web site: www.med.unc.edu/biochem. Applicants should apply online at gradschool.unc.edu/admissions.

Research Interests

The faculty research interests are diverse and include research in the following areas: cell signaling and growth control, DNA repair and replication, membrane biophysics and function, molecular regulation including transcriptional control, nervous system development and function, and protein structure/function, including enzymology. Model systems used by the faculty range from bacteria to mammals; techniques span molecular biology to physical biochemistry. A brochure describing the department and more detailed faculty research interests can be obtained by writing to the director of graduate studies of the Department of Biochemistry and Biophysics, or by visiting the department's Web site: www.med.unc.edu/biochem.

Facilities

The departmental research facilities are centered in the Genetic Medicine Building, which is within walking distance of other medical school departments, research centers, and the departments of biology, chemistry, and physics. The building is equipped with instruments for molecular biological, biochemical, structural, and biophysical research. Animal care facilities are available to support the department's research endeavors. Research and training support is provided by several core facilities on campus. Educational support is provided by the BBSP.

Courses for Graduate and Advanced Undergraduate Students

BIOC

442 Biochemical Toxicology (ENVR 442, TOXC 442) (3). See ENVR 442 for description.

601 Enzyme Properties, Mechanisms, and Regulation (3). Prerequisite, CHEM 430. Permission of the instructor for students lacking the prerequisite. Focuses on enzyme architecture to illustrate how the shapes of enzymes are designed to optimize the catalytic step and become allosterically modified to regulate the rate of catalysis.

631 Advanced Molecular Biology I (BIOL 631, GNET 631, MCRO 631) (3). See GNET 631 for description.

632 Advanced Molecular Biology II (BIOL 632, GNET 632, MCRO 632) (3). See GNET 632 for description.

643 Cell Structure, Function, and Growth Control I (CBIO 643, MCRO 643, PHCO 643, PHYI 643) (3). See CBIO 643 for description.

644 Cell Structure, Function, and Growth Control II (CBIO 644, MCRO 644, PHCO 644, PHYI 644) (3). See CBIO 644 for description.

650 Basic Principles: From Basic Models to Collections of Macromolecules (1.5). Prerequisite, CHEM 430. Required preparation, two semesters of physical chemistry or permission of the instructor. Basic molecular models and their use in developing statistical descriptions of macromolecular function. Course intended primarily for graduate students.

651 Macromolecular Equilibria: Conformation, Change, and Binding (1.5). Prerequisite, CHEM 430. Required preparation, two semesters of physical chemistry or permission of the instructor. Macromolecules as viewed with modern computational methods. Course intended primarily for graduate students.

652 Macromolecular Equilibria (1.5). Prerequisite, CHEM 430. Required preparation, two semesters of physical chemistry or permission of the instructor. Stability of macromolecules and their complexes with other molecules. Course intended primarily for graduate students.

655 Case Studies in Structural Molecular Biology (3). Prerequisite, CHEM 430. Permission of the instructor for students lacking the prerequisite. Principles of macromolecular structure and function with emphasis on proteins, molecular assemblies, enzyme mechanisms, and ATP enzymology.

660 Introduction to Light Microscopy (1). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. Fundamentals of optics and light microscope design for the novice student.

662 Macromolecular Interactions (1). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. Theory and practice of biophysical methods used in the study of interactions between macromolecules and their ligands, including surface plasmon resonance, analytical ultracentrifugation, and calorimetry.

663A Macromolecular NMR (1). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. Principles and practice of nuclear magnetic resonance spectroscopy: applications to biological macromolecule structure and dynamics in solution. Course intended primarily for graduate students.

663B Macromolecular NMR Practice (1). Prerequisite, BIOC 653. Permission of the instructor for students lacking the prerequisite. Lab section for BIOC 663A. Course intended primarily for graduate students.

664 Macromolecular Spectroscopy (1). Prerequisite, CHEM 430. Required preparation, two semesters of physical chemistry or permission of the instructor. Principles of UV, IR, Raman, fluorescence, and spin resonance spectroscopies; applications to the study of macromolecules and membranes. Course intended primarily for graduate students.

665 Advanced NMR Spectroscopy Course (1). Advanced NMR spectroscopy.

666 X-Ray Crystallography of Macromolecules (1). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. Principles of protein crystallography, characterization of crystals, theory of diffraction, phasing of macromolecular crystals and structure refinement. Course intended primarily for graduate students.

667 Macromolecular Crystallographic Methods (2). Prerequisite, BIOC 666. Permission of the instructor for students lacking the prerequisite. A combined lecture/laboratory workshop for serious students of protein crystallography. Course intended primarily for graduate students.

668 Principles of and Simulation of Macromolecular Dynamics (1). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. A combined lecture/computer lab treatment of the principles of macromolecular dynamics and structure as approached using the tools of molecular dynamics simulations. Course intended primarily for graduate students.

670 Biomolecular Informatics (1). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. A combined lecture/computer lab course introducing the methods and principles of biological data management as this relates to macromolecular sequence analysis. Course intended primarily for graduate students.

673 Proteomics, Protein Identification and Characterization by Mass Spectrometry (1). Prerequisites, BIOC 650–653. Required preparation, one semester of physical chemistry or permission of the instructor. A lecture module that introduces students to the basics of mass spectrometry as applied to protein science. Course intended primarily for graduate students.

674 Ion Channels Transporters (1). Ion channels transporters.

678 Electrical Signals from Macromolecular Assemblages (2). Prerequisites, BIOC 650–653. Permission of the instructor for students lacking the prerequisites. An intensive, six-hour per week introduction to the fundamentals of ion channel biophysics, including laboratory sessions to demonstrate principles and methods. Course intended primarily for graduate students.

Courses for Graduate Students

BIOC

700 Current Topics in RNA Structure, Function, and Technology (2). Critical reading and discussion of current literature related to the study of RNA structure, RNA-protein interactions, novel RNA functions, RNA as a therapeutic target/agent, and RNA methods.

701 Critical Analysis in Biochemistry (2). Permission of the instructor. Critical analysis of research papers from departmental seminar series, student presentations, meet seminar speakers, learn about departmental research and current techniques.

702 Advanced Biochemistry Laboratory (2–4). Prerequisite, CHEM 430. Permission of the department for nonmajors. Designed to introduce the student to research methods. Minor investigative problems are conducted with advice and guidance of the staff. May be repeated for credit.

703 Advanced Biochemistry Laboratory (2–4).Prerequisite, CHEM 430. Permission of the department for nonmajors. Designed to introduce the student to research methods. Minor investigative problems are conducted with advice and guidance of the staff. May be repeated for credit.

704 Seminars in Biophysics (2).Permission of the instructor. Students present seminars coordinated with the visiting lecturer series of the Program in Molecular and Cellular Biophysics.

705 Advanced Biophysics Laboratory (2–4).Permission of the program director. Designed to introduce students in the Molecular and Cellular Biophysics Program to research methods. Minor investigative projects are conducted with advice and guidance of the staff. May be repeated for credit.

706 Biochemistry of Human Disease (3).Required preparation, biochemistry. Permission of the instructor. Graduate level, involves lectures, critical readings, and discussions of biochemical aspects of human diseases. Core biochemical principles and cutting edge approaches are considered in the following: amyotrophic lateral sclerosis, Alzheimer's, cancer, cystic fibrosis, HIV, thrombosis and heart disease, schizophrenia, V(D)J recombination, and neglected diseases.

707 Cellular Metabolism and Human Disease (2). Open to 1st year BBSP or advanced graduate students with background in basic cellular biochemistry. Permission of the instructor. Addresses the role of cellular metabolism in human disease, including the roles and regulation of biochemical pathways. Recent advances will be emphasized. Diseases addressed will include cancer and diabetes.

711 Research Concepts in Biochemistry (2).Master's candidates in biochemistry and biophysics only. A series of lectures and exercises on formulating a research plan to attack a specific scientific problem, and on presenting the research plan in the form of a grant proposal.

712 Scientific Writing (3).Doctoral candidates in biochemistry and biophysics only. A course of lectures and workshops on the principles of clear scientific exposition with emphasis on the design and preparation of research grants.

715 Scientific Presentation (1). Senior graduate students present original research results as a formal seminar. Feedback on presentation effectiveness and style will be provided by faculty instructors and classmates.

720 The Biochemistry of HIV Replication, Inhibitors, and Drug Resistance (2). Seminar/discussion/literature course on structure-function of HIV proteins. Discussion of polymerases, proteases, protein-protein interactions, protein degradation pathways, protein-nucleic acid recognition, transcriptional control, RNA splicing and transport, and mechanisms of drug resistance.

721 Cell Regulation by Ubiquitination (2). Required preparation, two semesters of biochemistry. Lecture and literature-based discussion course on ubiquitin-mediated regulation of hormone receptor signaling, trafficking, and degradation.

722A Cellular and Molecular Neurobiology: Introduction and Electrical Signaling (NBIO 722A, PHCO 722A, PHYI 722A) (2).See NBIO 722A for description.

722B Cellular and Molecular Neurobiology: Postsynaptic Mechanisms-Receptors (NBIO 722B, PHCO 722B, PHYI 722B) (2). See NBIO 722B for description.

722C Cellular and Molecular Neurobiology: Synaptic Mechanisms & Intracellular Signaling (NBIO 722C, PHCO 722C, PHYI 722C) (2).See NBIO 722C for description.

723A Cellular and Molecular Neurobiology: Development of the Nervous System (NBIO 723A, PHCO 723A, PHYI 723A) (2). See NBIO 723A for description.

723B Cellular and Molecular Neurobiology: Anatomy and Function of Sensory and Motor Systems (NBIO 723B, PHCO 723B, PHYI 723B) (2).See NBIO 723B for description.

725 Signal Transduction (PHCO 725) (2). See PHCO 725 for description.

738 Nanomedicine (3).This course offers an introduction to the interdisciplinary field of nanomedicine for students with a physical, chemical, or biological sciences background. This course will emphasize emerging nanotechnologies and biomedical applications including nanomaterials, nanoengineering, nanotechnology-based drug delivery systems, nano-based imaging and diagnostic systems, nanotoxicology, and translating nanomedicines into clinical investigation.

740 Contemporary Topics in Cell Signaling: Phosphorylation Control (1).Required preparation, coursework in biochemistry, pharmacology, and/or cell & molecular biology. Permission of the instructor. This graduate-level course is an in-depth analysis of how protein kinases and protein phosphorylation regulates key aspects of cell signaling. This class is one of the "Contemporary Topics in Cell Signaling" modules.

741 Contemporary Topics in Cell Signaling: GTPases (1).Required preparation, coursework in biochemistry, pharmacology, and/or cell & molecular biology. Permission of the instructor. This graduate-level course conveys principles of signal transduction controlled by GTPases and emphasizes in-depth discussion of current literature and unanswered questions. This class is one of the "Contemporary Topics in Cell Signaling" modules.

742 Contemporary Topics in Cell Signaling: Cell Cycle Control (1).Permission of the instructor. Required preparation, coursework in biochemistry and/or cell & molecular biology. This graduate-level course conveys principles of eukaryotic cell proliferation control emphasizing in-depth discussion of current literature and unanswered questions. This class is one of the Contemporary Topics in Cell Signaling modules.

743 Contemporary Topics in Cell Signaling: Signaling Networks (1).Acquire the scientific vocabulary of the signaling network field. Master key concepts from mathematical characterization of signaling circuits. Develop and apply critical analysis skills.

744 Topics on Stem Cells and Development (1).Required preparation, coursework in genetics, cell biology, and molecular biology. Permission of the instructor. Course addresses key issues in developmental biology focused on the role of stem cells and emphasizes in-depth discussion of current literature and unanswered questions. One of the Contemporary Topics in Cell Signaling modules.

The following seminar courses are designed for students majoring or minoring in biochemistry who wish to further their knowledge in particular areas. Unless otherwise stated, two semesters of biochemistry are prerequisites for seminar courses. Most of these courses are given in alternate years by interested staff members. Unless otherwise stated, these seminars may not be repeated for credit. Seminar courses provide teaching experience, which is required for a graduate degree in biochemistry and biophysics. In addition, the courses provide experience in giving a critical review of the current literature.

802 Seminar in the Phase Problem in X-Ray Crystallography (2). Permission of the instructor. Image formation is treated from a quite general point of view, drawing from Fourier transform methods used in X-ray crystallography. Isomorphous replacement, multiple wavelength anomalous scattering, and Bayesian direct methods are covered. One two-hour seminar a week.

803 Seminar on Cell Signaling (2). Required preparation, two semesters of biochemistry. Signal transduction in embryonic development.

804 Seminar in DNA-Protein Interactions (2). Required preparation, two semesters of biochemistry. Review of current literature on structural, thermodynamic, and kinetic aspects of binding to DNA of proteins involved in replication, regulation, recombination, and repair.

805 Molecular Modeling (MEDC 805) (3). Prerequisites, MATH 231, 232, and CHEM 481. Introduction to computer-assisted molecular design, techniques, and theory with an emphasis on the practical use of molecular mechanics and quantum mechanics programs.

806 Macromolecular Modeling (MEDC 806) (3). See MEDC 806 for description.

807 Seminar in Cellular Responses to DNA Damage (2). Required preparation, graduate-level courses (one each) in molecular biology and biochemistry. A seminar course on the enzymology of DNA repair and damage tolerance and the regulation of genes involved in these processes. Both classic and recent literature are discussed.

808 From Force to Phenotype: How Biological Structures Respond to Physical Force (2). Literature/discussion course on integrating physics with biology, and the challenge of merging structural dynamics with living cell phenotypes. Forces and biological outcomes will be considered through specific examples.

901 Research in Biochemistry (3–9).Permission of the department.

902 Research in Biochemistry (1–21). Permission of the department. Six or more hours a week throughout both semesters.

992 Master's (Non-Thesis) (3).

994 Doctoral Research and Dissertation (3).