Prof Frances Brodsky
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. Studies from the lab have characterized these known pathways and 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. 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.
Frances Brodsky taught Immunology at UCSF for 25 years. She is currently teaching molecular cell biology at UCL.
- University of Oxford
- Doctorate, Doctor of Philosophy | 1979
- Harvard University
- First Degree, Bachelor of Arts | 1976