Stanford University Biochemistry Stanford, CA Overview The total enrollment at Stanford University is more than 14,000, including approximately 7,500 graduate students. There are nearly 40 students in the biochemistry Ph.D. program. The Location and Community Programs of Study and Degree Requirements Courses in biochemistry, biophysics, and molecular biology are taught by the faculty, and advanced courses in specialized areas are also offered. These include the chemistry and biology of proteins, nucleic acids, and membranes; biological regulatory mechanisms; mechanistic aspects of enzyme action; bioinformatics and genomics; and molecular and genetic aspects of cellular and developmental biology. The program of study is created in consultation with the adviser to best fulfill each student's educational goals. Graduate students learn about teaching by assisting in the departmental teaching programs. All of the bioscience departments and programs at Stanford participate in a flexible admissions program. This unique program offers first-year graduate students immersion into a particular research environment that matches the student's interests in a home program while also offering a choice of laboratory rotations and a research adviser from all of the more than 100 bioscience research laboratories at Stanford. For more information about biosciences and about flexible admissions at Stanford, students should consult the Web site for the bioscience programs at http://med.stanford.edu/biosciences/index.html. Facilities & Resources The Department of Biochemistry is located in the Arnold and Mabel Beckman Laboratories for Biochemistry in Stanford's Beckman Center for Molecular and Genetic Medicine. The Department of Biochemistry is joined there by three interrelated academic groups: the Departments of Developmental Biology and of Molecular and Cellular Physiology and the Howard Hughes Unit in Molecular and Genetic Medicine. Housing nearly 40 faculty members and their research teams, the Beckman Center is a focal point for biological research at Stanford. Expenses and Aid Financial Aid: Housing/Living Expenses: How to Apply Students must see to it that all application materials (transcripts, scores, etc.) are received by the department before December 16. All applicants are notified by April 15. The department requires scores on the Graduate Record Examinations General Test as well as the Subject Test in biology, chemistry, or biochemistry, cell and molecular biology. Students must take these exams by the October/November test dates to ensure that their scores are received in time. Who to Contact The Graduate Admissions Program 650-723-4291 E-mail: ck.gaa@forsythe.stanford.edu The Faculty • Robert L. Baldwin, Professor Emeritus; D.Phil., Oxford, 1954. • Paul Berg, Professor Emeritus; Ph.D., Western Reserve, 1952. • Patrick O. Brown, Professor; Ph.D., 1980, M.D., 1982, Chicago. The development and application of microarray-based methods and computational tools for systematic and quantitative studies of gene expression and biological regulation. Genomic and biochemical approaches are used to investigate the basic mechanisms that regulate the genome's expression program, explore basic questions in human biology, and to develop new ways to diagnose and treat cancer and other diseases. • Douglas L. Brutlag, Professor; Ph.D., Stanford, 1972. Application of information science to DNA/protein sequences and structures in order to understand the flow of information from genome to phenotype. Of particular importance are the problems of predicting structure and function from sequence, simulating protein-ligand docking, and protein-protein and protein-DNA interactions. The lab is also involved in discovering conserved protein motifs and conserved DNA motifs. The DNA motifs studied are involved in transcription factor finding sites, transcription start and termination sites, and splice donor/acceptor sites. Critical methods used include comparative genomics, machine learning, simulation, information theory, and statistics. • Gilbert Chu, Professor; Ph.D., MIT, 1973; M.D., Harvard, 1980. Cells recognize and respond to DNA damage in order to survive and maintain genomic integrity. To understand repair pathways for DNA damaged by ultraviolet radiation (UV) and ionizing radiation (IR), purified proteins, cell extracts, and intact cells are utilized. These pathways include nucleotide excision repair and double-strand break repair, which are important for cell survival, suppressing mutagenesis, and generating immunological diversity. To understand transcriptional responses to DNA damage, the lab has developed statistical methods for analyzing microarray data. The lab uses transcriptional responses to predict cancer risk and risk for toxicity from anticancer treatment. • Ronald W. Davis, Professor; Ph.D., Caltech, 1970. Functional genomics and technology development. As a model system, the lab uses Saccharomyces cerevisiae to apply DNA microarrays and other new technology to analyze the whole genome for phenotype of deletions, RNA expression levels, protein levels, metabolic regulation, DNA replication, protein-protein interaction, and drug sensitivity. A major program is the quantitative phenotypic analysis of yeast deletion. The lab has deleted 95 percent of the yeast genes and replaced them with a molecular bar code that allows the lab to analyze a mixture of all deletion simultaneously. This program is a model for functional genomics. A program in genome profiling of drug and toxin interactions has been established. In addition, a new program in ecological genomics is being developed. New technology for very high throughput and low-cost simple nucleotide polymorphism has been developed to be applied to complex genetic problems in model organisms and humans. • James E. Ferrell Jr., Professor; Ph.D., 1984, M.D., 1986, Stanford. Cell signaling and cell cycle regulation. The lab is studying signaling proteins that control mitosis and meiosis. The goal is to determine how the biochemical properties of individual signaling proteins and the organization of these proteins into cascades and loops generates systems-level behaviors such as amplification, adaptation, and oscillations. Experimental work is carried out in Xenopus oocytes, eggs, and egg extracts-systems which are well suited to quantitative biochemical analysis. These experimental studies are complemented with computational approaches. • Pehr Harbury, Associate Professor; Ph.D., Harvard, 1994. Structural determinants of protein folding, design, and small-molecule recognition. The molecular mechanisms that confer specific shapes on proteins and determine how proteins recognize small molecules are being studied. The goal is to elucidate predictive principles by which novel structures and catalytic properties can be conferred accurately on designed polypeptides and to achieve the rational design of ligands for proteins of known conformation. The lab relies primarily on three tools: the computational engineering of structures at atomic resolution, which is made possible by the advent of classical molecular mechanics potentials; biophysical characterization of peptide proteins composed from an expanded amino acid alphabet; and the generation and screening of combinatorial libraries. • Daniel Herschlag, Professor; Ph.D., Brandeis, 1988. RNA folding; RNA and protein catalytic mechanisms; global RNA processing. Biochemical and biophysical approaches are taken to understand mechanisms of simple and complex RNA and protein enzymes and RNA folding. These approaches include single molecular fluorescence and force measurements, small-angle X-ray scattering, vibrational spectroscopy, and several other techniques. These approaches complement in-depth kinetic and thermodynamic studies. Cellular RNA processing events are dissected using DNA microarrays to simultaneously follow all yeast RNAs. • David S. Hogness, Professor Emeritus; Ph.D., Caltech, 1952. • Dale Kaiser, Professor; Ph.D., Caltech, 1955. Regulation of multicellular development; how cellular patterns are formed and how cells in an embryo coordinate their activities so that the right cell is in the right place at the right time. Myxobacteria are one of the simplest organisms that exhibit multicellular development with cellular differentiation and spatially localized gene expression. They permit both biochemical and genetic studies of cell-cell interactions necessary for development and differentiation. Two extracellular factors needed at different times for transcription of developmentally regulated genes have been purified. Their signal transduction pathways are being dissected. • Arthur Kornberg, Professor; M.D., Rochester, 1941. Inorganic polyphosphate (poly P) is a linear polymer of many tens or hundreds of orthophosphate (Pi) residues linked by high-energy, phosphoanhydride bonds. Likely a prominent precursor in prebiotic evolution, poly P is now found in volcanic condensates, deep-oceanic steam vents, and in every living thing-bacteria, fungi, protozoa, plants, and mammals. Among poly P functions are kinase donor to glucose, nucleoside diphosphates, and proteins; phosphate reservoir; divalent metal (Ca®MD+SU¯++®MD-SU¯, Mg®MD+SU¯++®MD-SU¯, Mn®MD+SU¯++®MD-SU¯) chelator; and component of a membrane complex in metal ion channels and bacterial transformation. Recent studies have disclosed three additional roles: "alarmone" in response to stresses and deficiencies; adaptations for survival in the stationary phase; and motility, quorum sensing, biofilm formation, and virulence in bacterial pathogens tested. Current studies focus on the biochemical mechanisms responsible for those many functions of poly P and in animal cells and in sporulation. • Mark A. Krasnow, Professor; Ph.D., 1983, M.D., 1985, Chicago. Genetic, genomic, and biochemical analysis of epithelial morphogenesis, using the Drosophila tracheal (respiratory) system and mouse lung as models. The goals are to understand the cellular and molecular basis of how epithelial cells migrate and find their targets, how the cells assemble into tubes, how tubes interconnect, and how these processes are regulated by tissue oxygen need. • I. Robert Lehman, Professor Emeritus; Ph.D., Johns Hopkins, 1954. DNA replication in eukaryotes. Research in the lab is aimed at understanding the mechanism by which the genome of herpes simplex virus type 1 (HSV-1) is replicated. The linear HSV-1 genome circularizes following infection and undergoes θ-type replication dependent upon one or more of the three origins. In the second phase, the circular products of θ replication engage in rolling-circle replication promoted by the virus-encoded enzymes to produce concatameric molecules that are then cleaved to unit length and packaged into viral particles. The lab has found that a complex containing the virus-encoded enzymes that it has isolated from HSV-1 infected human cells can promote the rolling-circle phase of HSV-1 DNA replication. Research aims are to purify the complex to homogeneity and determine its components, particularly those contributed by the host cell, and to identify the factors that promote the switch in the mode of DNA replication from θ to rolling circle. There is some indication that a recombinational event may be involved. • Suzanne R. Pfeffer, Professor; Ph.D., California, San Francisco, 1983. Biochemistry of intracellular transport. Research is aimed at the molecular mechanisms of protein targeting to distinct intracellular compartments. Protein transport between endosomes and the Golgi apparatus is studied in a cell-free system to discover proteins that catalyze vesicular transport. The ras-like GTPase, rab9, and a rab-specific, nucleotide exchanger is required. Also being investigated is how sixty different Rab GTPases are delivered to distinct compartments in mammalian cells and how Rab GTPases function in prostate and breast cancer and in Niemann-Pick Type C disease. • James A. Spudich, Professor; Ph.D., Stanford, 1968. Biochemical, molecular, genetic, and structural studies of actin, myosin, and associated regulatory proteins from eukaryotic cells. Work focuses on the design and development of in vitro assays for ATP-dependent movement of purified myosin on filaments reconstituted from purified actin. This includes the development of laser traps for single-molecule analyses. Myosin gene cloning and expression of site-directed mutagenized forms, which are analyzed for altered functions, is also carried out. Emphasis is on the molecular basis of energy transduction that leads to myosin movements on actin filaments and also on regulation of actin and myosin interactions and of their assembly states, with particular interest in Dictyostelium chemotaxis, cytokinesis, and other forms of cell movement. • Aaron Straight, Assistant Professor; Ph.D., California, San Francisco, 1998. Eukaryotic chromosome structure and function. Cells have devised extraordinary mechanisms to ensure that chromosomes are faithfully replicated and equally segregated during cell division. Study is centered on how chromosome structure contributes to the fidelity of cell duplication. Work focuses on understanding how kinetochores control the equal distribution of chromosomes by interacting with microtubules of the mitotic spindle. Current research involves understanding how kinetochore position is specified by genetic and epigenetic determinants, the biochemical mechanisms of kinetochore assembly, and how kinetochores harness the forces required to segregate chromosomes during anaphase. • Julie A. Theriot, Assistant Professor; Ph.D., California, San Francisco, 1993. Mechanisms of actin-based cell motility; cell biology of host-pathogen interactions. Polymerizing networks of actin filaments are capable of generating significant amounts of force that can be used by eukaryotic cells and their prokaryotic pathogens to change shape or to move, using the nonequilibrium protein polymerization reaction to transduce chemical energy into mechanical energy without the assistance of any molecular motor proteins. Projects focus on understanding the biochemical and biophysical mechanisms of force generation by actin polymerization and the large-scale self-organization and polarization of actin networks, both at the leading edge of motile cells and on the surfaces of bacterial intracellular pathogens that include Listeria monocytogenes and Shigella flexneri. |