Frances M.
Brodsky, D.Phil.
Professor of
Biopharmaceutical Sciences, Immunology and Microbiology,
and Pharmaceutical Chemistry



Contact Information:
frances.brodsky@ucsf.edu
Tel: (415) 476-6405
Fax: (415) 476-6185
HSW-1527, Box 0446

Links:
Lab website
Biomedical Sciences
Tetrad

Publications:
Selected
Complete

Work in the Brodsky laboratory focuses on understanding the mechanism of how proteins are selectively transported between the external and internal membranes of a eukaryotic cell. This selective transport influences cellular uptake of macromolecules by receptor-mediated endocytosis and the processing and presentation of antigens to the immune system. One of the major pathways by which proteins are selectively trafficked through intracellular membrane compartments is controlled by the formation of clathrin-coated vesicles (CCVs).

We are analyzing CCV formation at the molecular level, with a major emphasis on the defining the biochemistry of the clathrin molecule whose self-assembly provides the driving force for membrane vesicle formation and protein sorting. Recent advances in the laboratory include the resolution of the structure of the self-assembling portion of the clathrin molecule (in collaboration with the Fletterick laboratory), identification of potential salt-bridges that control clathrin self-assembly and identification of a phosphorylation reaction through which SRC kinase regulates clathrin assembly.

We are also studying the biochemistry of a novel clathrin-like molecule that appears to play a role in membrane traffic during muscle differentiation. With the structure of part of the clathrin molecule in hand and crystals of remaining fragments ready to analyze, we are poised at the brink of understanding clathrin self-assembly at molecular resolution. This analysis will lead to future studies of how regulatory proteins control CCV formation in the cell.

Our studies of clathrin protein fragments have also led to the design of mutant molecules that inhibit the function of clathrin and its homologue in cells. These tools have made it possible to define the role of these clathrins in a number of cellular activities. Current studies focus on the role of CCVs during infection by intracellular parasites and by viruses. Thus our structural and biochemical approaches have made it possible to analyze the role of membrane traffic in the pathogenesis of infectious organisms including HIV, Chlamydia trachomatis and Toxoplasma gondii.