Prof Frances Brodsky
Director of Div of Biosciences/ Professor of Cell Biology
Structural & Molecular Biology
Div of Biosciences
- Joined UCL
- 1st Oct 2013
The Brodsky Laboratory has made significant contributions to understanding the structure, function, and regulation of clathrin proteins. Research in the laboratory continues to investigate novel and conventional clathrin functions that are important for human health. Clathrin-coated vesicles control protein traffic from the plasma membrane and through intracellular compartments, influencing cell-cell interactions and affecting diverse physiological processes. Recent studies from the lab reveal a wider range of clathrin functions including actin organisation during infection and cell migration, a specific role for a novel clathrin isoform in glucose metabolism related to Type 2 Diabetes, and roles in oncogenesis through microtubule interactions. Our long-term goal is to understand the molecular basis for clathrin-mediated membrane traffic and its regulation.
Clathrin proteins have a triskelion (three-legged) shape and self-assemble into lattices. Each triskelion comprises three clathrin heavy chain subunits, which mediate self-assembly and coat formation. The canonical clathrin heavy chain subunit, CHC17, binds three light chain subunits. However, the functions of the clathrin light chain subunits, and particularly their diversity, are not fully defined. In vertebrates, genes CLTA and CLTB encode clathrin light chains CLCa and CLCb, which are 40% divergent in sequence. One major research programme in our group aims to understand how vertebrate light chain diversity contributes to tissue specificity of clathrin-mediated membrane traffic.
In humans and other vertebrates there is a second isoform of clathrin heavy chain, CHC22. Recent studies from our laboratory indicate that in human muscle and fat cells, CHC22 plays an important role in the insulin-regulated trafficking of the GLUT4 glucose transporter. In response to insulin, GLUT4 is inserted into the plasma membrane, where it transports glucose from the blood into the cell. Disrupted GLUT4 trafficking may underlie the insulin resistance that precedes Type 2 Diabetes. Current studies suggest that CHC22 is involved in controlling GLUT4 retention and insulin-stimulated release. Our second major research programme aims to explore this hypothesis, and to elucidate the biochemical, cellular, and physiological roles of CHC22 clathrin.
- University of Oxford
- , | 1979
- Harvard University
- , | 1976
The Brodsky Laboratory has been studying clathrin biochemistry, cell biology, and physiology for nearly 30 years. The group was based at the University of California, San Francisco (UCSF) until 2014, when Professor Brodsky accepted a position as Professor of Cell Biology and Director of the Division of Biosciences at University College London (UCL).
Frances Brodsky graduated from Harvard University with a degree in Biochemical Sciences in 1976, and earned her doctorate from Oxford University under a Marshall Scholarship in 1979. Brodsky's graduate work with immunologist Sir Walter Bodmer applied the then-novel technology of monocolonal antibodies to study human histocompatability molecules (HLA). Brodsky worked as a postdoctoral fellow, first with Jack Strominger at Harvard, and then with Peter Parham at Stanford University, where she discovered that the clathrin protein controls intracellular transport important for HLA stimulation of immune responses. Brodsky then joined Becton Dickinson Immunocytometry Systems as a Programme Manager, where she ran her own lab for four years before becoming an Assistant Professor at UCSF. Brodsky was awarded tenure in 1994, and was a full professor at UCSF until 2014, when she joined UCL. Prof. Brodsky has served as a member and chair of numerous boards, study sections, and advisory committees for organisations such as the U.S. National Institutes of Health and the Pew Scholars Program. In 2000, Brodsky co-founded the scientific journal Traffic, which specialises in intracellular transport, and now serves as Reviews Editor. Research in the Brodsky lab continues to focus on the biochemical and physiological functions of clathrin.