Who We Are
Our most basic research begins with Buzz Baldwin who would like to understand how proteins fold. Pehr Harbury continues to attack this question, with the goal of defining the rules by which proteins achieve their fully folded, three dimensional structures. Once proteins and RNA molecules have folded, they are capable of catalyzing chemical reactions over a million fold. How molecules act as catalysts is the primary interest of Dan Herschlag. Jim Spudich is specifically interested in how the enzyme, myosin, acts as a catalyst and couples the energy derived from ATP hydrolysis to drive muscle contraction, cytokinesis, and other forms of cell movement. Spudich is combining biophysics, molecular genetics, cell biology and biochemistry to understand single molecule function and its consequences, in relation to the actin-based cytoskeleton, for an entire cell. Aaron Straight is also interested in understanding the process of cell division. His work investigates how the unique structure of the eukaryotic kinetochore is generated and how it mediates chromosome transmission during mitosis. His laboratory also investigates the complex interplay between chromosomes, the cytoskeleton and the cell membrane that ensures proper cell division during cytokinesis.
Julie Theriot shares with Spudich and Straight an interest in cytoskeletal function--she would like to understand the molecular events that underlie the ability of pathogenic microorganisms such as Listeria and Shigella to trigger actin polymerization at their tails, a process that propels the bacteria through the cytoplasm of infected cells. Analysis of the cytoskeleton leads one immediately to three dimensional cellular organization, an interest also shared with Suzanne Pfeffer. Pfeffer is studying how small GTPases of the Rab family control receptor traffic in human cells. She is studying specific proteins that function to form receptor-containing transport vesicles, and to help vesicles identify their intracellular targets.
Turning to processes that take place within the cell's nuclear compartment, Bob Lehman is working to understand the mechanism of DNA replication. Lehman would also like to understand the molecular events responsible for the latency of many viruses such as Herpes. DNA replication is closely linked to DNA recombination, the love of Paul Berg for many years. Gil Chu is studying the repair of DNA and its role in generating immunological diversity.
Beyond the three dimensional single cell, one next considers cell:cell interactions, the focus of work by Mark Krasnow and Dale Kaiser. Krasnow is working to understand how a set of epithelial cells start as a patch on the surface of a Drosophila (fruit fly) embryo convert themselves into a branching tubular array to form the trachea of this organism. Dale Kaiser is similarly working to understand the communication between Myxococcus bacterial cells that regulates their motility and gene expression to build multicellular structures. Again, in both cases, these labs are using first genetic then biochemical and cell biological approaches to understand multicellular development.
Finally, in moving beyond cells and tissues to the whole organism we must consider entire genomes. The Biochemistry Department houses several of the most exciting research groups in this area. Ron Davis, Gil Chu and Pat Brown are utilizing novel technologies for analyzing mutations, gene expression and protein interaction in yeast and human cells. These studies address a vast array of interesting questions, often with important consequences for our understanding and possible treatment of human disease. And interpreting all of the new genome information in terms of predicting functionality falls in the bailiwick of Doug Brutlag, who is a pioneer in the new field of Bioinformatics. All of us studying complex biological questions will save money and time due to the huge influx of data provided by the genome projects. Indeed, when we discover novel enzymes we now turn to the computer to sequence the rest of our proteins, to try to detect homology or to obtain phenotype information and cDNA clones.
In our view, the future of Biochemistry will be to address three dimensional questions--how proteins assembled into higher order structures, how subassemblies and organelles are localized in cells, and how protein subassemblies are generated at the right time and place to accomplish regulated cell proliferation and division. How do cells communicate to build tissues and regulate each other in response to regulatory clues? By understanding how proteins fold and interact, distribute within the cytoplasm and function as machines, we will make great strides in terms of understanding physiology in molecular terms.
The future will also need to integrate new approaches into our analysis. Systems behave differently than small groups of molecules, and engineers will help us to understand such complexities. Databases will be needed to handle the huge and complex sets of information that Biologists and Biochemists will be generating. Our view of the world, based on the behavior of populations will be enhanced by looking at the modes of action of single molecules. In all of this, we are excited about new initiatives at Stanford to support and promote a multifaceted approach to bring together physicists, engineers, biochemists, chemists and biologists to look at the three dimensional cell and take our biochemical questions to the next level of analysis, integration, and comprehension.
- Mark Krasnow, Professor and Chair of Biochemistry
