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The future of Biochemistry is to understand how molecules direct all cellular processes, from gene expression to cellular organization to tissue formation and organogenesis. This begins with an understanding of how proteins fold and how enzymes work. But cells are not bags of enzymes; rather, biochemical processes are compartmentalized. For example, signal transduction involves signaling complexes held together by scaffolds, anchors and adaptor proteins. These macromolecular assemblies must be studied in a functional sense to fully understand cell regulation. Biochemical processes are also ordered in relation to the three dimensional organization of a cell. How do cells achieve their polarity, and what molecular constituents drive their ordered division? Now that we can analyze the expression of entire genomes in a single experiment, what kinds of questions can we ask that could never have been asked before?
Students in our department are given opportunities to investigate the biochemical and structural basis of molecular, cellular and developmental processes at a variety of levels of detail and in a variety of organisms ranging from bacteria to mammalian cells. Ongoing research includes studies of protein and RNA folding and catalysis by protein enzymes and ribozymes; DNA replication and recombination; gene regulation; cell motility and molecular motors; protein targeting and transport in the cell; cell adhesion and recognition; intercellular signaling; methods of isolating, and analyzing and altering genes and entire genomes.
The department’s graduate program emphasizes research training and continues to spawn leading researchers in academia and biotechnology. Students design their own programs of study to best suit their educational goals and select the research group for their thesis following research rotations and in consultation with their graduate advisor and other faculty. Concurrent with thesis research, students formulate original research proposals, take classes in biochemistry, structural biology, cell biology and genetics, serve as teaching assistants, attend a journal club with presentations by faculty, students and postdoctoral fellows, and attend seminars by outside speakers. Annual department-wide retreats serve as a forum for presentations by all research groups. Laboratory rooms and equipment are shared by all research groups to promote interactions and exchange of ideas between students, postdoctoral fellows and faculty.
For more information contact:
Joella Ackerman
Department of Biochemistry
Beckman Center, B400
Stanford, CA 94305-5307
(650) 725-9058
(650) 723-6783 (fax)
joella.ackerman@stanford.edu
http://biochemistry.stanford.edu/
Faculty and their Research Interests
Patrick Brown is developing and applying genomic approaches to map global gene expression programs and to understand the architecture and the detailed molecular mechanisms of their regulation. The lab is also exploring new approaches to the classification, detection, diagnosis and treatment of human diseases, developing ex vivo culture systems for reproducing human tissue microenvironments, and systematically investigating the microbial ecology of the human body.
Douglas Brutlag is developing computational methods for predicting gene function and gene regulation from sequence. These methods learn conserved patterns of protein motifs and common DNA regulatory signals that can be used to predict function and regulation in newly sequenced genomes.
Gilbert Chu is studying pathways for DNA repair: one that excises bulky DNA adducts for nucleotide excision repair, and one that resolves DNA ends for both double-strand break repair and V(D)J recombination, a process that generates immunological diversity. The research has implications for xeroderma pigmentosum, cancer, and immunological disorders.
Ronald Davis is devising new technologies and instrumentation toward rapid whole genome sequencing, expression, proteomics, and functional analysis. These novel approaches are being applied to yeast, humans, plants and various pathogens.
James Ferrell, Jr. is studying mitosis and meiosis in Xenopus embryos and human cell lines. His lab is particularly interested in trying to understand how complex biochemical behaviors like switching and oscillations emerge out of small networks of regulatory proteins.
Pehr Harbury is trying to engineer proteins and small-molecule drugs at atomic resolution through a combination of structural calculations and combinatorial library synthesis. His goal is to elucidate predictive principles by which novel shapes and catalytic properties can be conferred accurately on designed polypeptides.
Dan Herschlag is trying to unravel the fundamental chemical and physical principles that underlie the folding and function of biological catalysts. Folding of RNA enzymes, or ribozymes, is studied as is catalysis by RNA and protein enzymes. A battery of chemical and biophysical approaches are brought to bear on these problems, including single molecule fluorescence, small angle x-ray scattering, x-ray crystallography, EPR, NMR, and computation. Also, the eukaryotic gene expression program is under investigation genome-wide studies in collaboration with Pat Brown to unravel the logic underlying control and coordination of RNA processing and RNA/protein interactions.
Chaitan Khosla studies the biosynthesis of polyketide antibiotics with the concomitant goal of engineering polyketide synthases to make new bioactive natural products. He also seeks to understand the biochemistry of Celiac Sprue, an autoimmune disease of the small intestine, and to translate these insights into therapeutic solutions for this unmet medical need.
Mark Krasnow is using genetic, genomic, cellular, and biochemical analysis to study epithelial morphogenesis, using the Drosophila tracheal (respiratory) system and the mouse lung as models. The goals are to understand how epithelial cells migrate and find their targets, how migrating cells assemble into tubes, how tube size and shape is controlled, and how oxygen regulates the process.
Sharon Long studies chemical signals and cellular responses between bacteria and eukaryotic hosts in the development of symbiotic root nodules by Rhizobium bacteria and leguminous plants. Her lab employs methods that include natural products chemistry, protein biochemistry, genetics and genomics, and cell imaging to analyze nodulation and nitrogen fixation. They are particularly interested in differentiation, transcription, and cell morphogenesis.
Suzanne Pfeffer is interested in the mechanisms by which receptors traffic between membrane-bound compartments in human cells. Her lab studies how Rab GTPases function with other proteins to help transport vesicles form and identify their targets. She is also studying the NPC1 membrane protein that when mutated, causes Niemann Pick Type C disease in humans.
James A. Spudich focuses on the myosin family of molecular motors, their roles in vivo and the mechanism by which they facilitate cell contraction, cytokinesis, and a variety of other forms of cell movement. The Spudich lab is using a multifaceted approach that includes the latest biophysical technology that permits analysis of single molecules in action.
Aaron F. Straight is studying the process of cell division including problems in chromosome structure, mitotic chromosome segregation and cytokinesis. The Straight lab uses biochemistry, microscopy and cell biological approaches to understand chromatin organization, chromosome dynamics and the mechanisms of cell cleavage.
Julie A. Theriot is studying the interactions between infectious bacteria and the human host cell actin cytoskeleton. Listeria monocytogenes and Shigella flexneri share a common mechanism of invasion and actin-dependent intercellular spread in epithelial cells. The goal is to understand the biochemical basis of actin-based motility by these bacteria and the biophysical mechanism of force generation.
Emeritus Faculty
Robert L. Baldwin is studying the roles of peptide backbone solvation and peptide H-bonds in the energetics of protein folding.
Paul Berg, Nobel laureate, is studying the molecular mechanisms of genetic recombination with a view to improving the efficiency of genomic modifications in mammalian cells and whole animals.
David Hogness is interested in the molecular basis of Drosophila development, including genetic networks that control the larva-to-fly metamorphosis and their activation by the steroid hormone ecdysone via its receptor.
Dale Kaiser is investigating the coordination of multicellular development in a bacterial system. He is trying to understand how intercellular signaling controls cell movement and gene expression.
Arthur Kornberg, Nobel laureate, currently directs a major research effort aimed at understanding polyphosphate biosynthesis, degradation, and physiological function. Polyphosphate comprises a large fraction of cell mass, yet we know little about its function.
Robert Lehman is investigating the mechanism of DNA replication in eukaryotes, with particular emphasis on the replication of herpes virus DNA.
