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UCL Division of Biosciences

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Prof Frances Brodsky

Professor of Cell Biology

Structural & Molecular Biology

Div of Biosciences

Joined UCL
1st Oct 2013

Research summary

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.

Teaching summary

Frances Brodsky taught Immunology at UCSF for 25 years. She is currently teaching molecular cell biology at UCL.

Education

University of Oxford
Doctorate, Doctor of Philosophy | 1979
Harvard University
First Degree, Bachelor of Arts | 1976

Biography

Frances Brodsky graduated from HarvardUniversity with a degree in Biochemical Sciences in 1976, and earned herdoctorate from Oxford University under a Marshall Scholarship in 1979.  Brodsky's graduate work with immunologist SirWalter Bodmer applied the then-novel technology of monoclonal antibodies tostudy human histocompatability molecules (HLA). Brodsky worked as a postdoctoral fellow, first with Jack Strominger atHarvard, and then with Peter Parham at Stanford University, initiating herresearch on clathrin biochemistry. Brodsky then joined Becton Dickinson Immunocytometry Systems as aProgramme Manager, where she ran her own lab for four years focussing onclathrin and intracellular membrane traffic in the immune response, which shecontinued as an Assistant Professor at University of California, San Francisco(UCSF).  Brodsky was awarded tenure in1994, and was a full professor at UCSF until 2014, when she joined UniversityCollege London (UCL) as Director of the Division of Biosciences (2014-2020),where she continues to run her laboratory and teach.  Prof. Brodsky has served as a member andchair of numerous boards, study sections, and advisory committees fororganisations such as the U.S. National Institutes of Health, the HumanFrontiers Science Program, the Searle Scholars Program and the Pew ScholarsProgram.  She is an elected fellow of theAcademy of Medical Sciences (serving on council, 2018-2020 and as InterimVice-President International, 2020-2021) and member of EMBO.  In 2000, Brodsky co-founded the scientificjournal Traffic, which specialises in intracellular transport, and now served asan editor and on the board until 2020. Research in the Brodsky lab continues to focus on the biochemical andphysiological functions of clathrin.

Publications