宅男视频

• The molecular basis for clathrin function.
• Clathrin proteins' roles in physiology, including lymphocyte function, glucose metabolism and oncogenesis, and potential therapeutic value.
• The genetic diversity and evolutionary origins of the clathrin proteins, and the functional consequences of clathrin subunit diversity.

Towards these goals, we employ a range of scientific techniques, including biochemical analysis, protein production and purification, mass spectrometry, tissue culture and cellular assays, electron and confocal light microscopy, physiological models and human and evolutionary genetics.

In 2014, Professor Brodsky moved from the University of California San Francisco to join UCL as Director of the听Division of Biosciences, finishing her second term as Director in December 2020. The laboratory fully relocated to 宅男视频 in 2015 and is part of the Department of Structural and Molecular Biology in the Division of Biosciences, where Brodsky continues her research programme and teaching.

"Studying the remarkable self-assembling clathrin proteins has led us in diverse research directions, crossing interfaces between biochemistry, cell biology, immunology and metabolism. It is exciting and gratifying that our basic molecular studies are now revealing intracellular mechanisms and pathways that are directly relevant to several human diseases including infection, type 2 diabetes and cancer." - Frances Brodsky

Clathrins for Non-Scientists

At the Brodsky Lab, we are passionate about making our research as widely available and understood听as possible. We have "translated" what our lab does into language we hope anyone can understand.听

Read about Clathrins for Non-Scientists

Our Research

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. Specifically, the lab is currently focussing on the following projects:

Project #1 鈥� CHC22-dependent trafficking of the insulin-sensitive GLUT4 glucose transporter
听

Humans have two isoforms of the clathrin heavy chain (CHC), known as CHC17 and CHC22. CHC17 is ubiquitously expressed and is involved in a wide range of intracellular trafficking activities, most notably receptor-mediated endocytosis. In contrast, CHC22 is primarily expressed in muscle cells and performs a more specialised function in trafficking the GLUT4 glucose transporter to an insulin-sensitive, intracellular storage compartment. Whilst CHC17 has been extensively studied, much less is known about how CHC22 operates. One of the main research activities of our lab is utilising a combination of structural biology, biochemistry, genomics and cell biology to elucidate the mechanism, function, and regulation of CHC22 and its dependent pathways.

To read more, take a look at the听summaries of our most recent publications on CHC22

Project #2 鈥� Physiological functions of the clathrin light chains

The canonical form of clathrin is composed of CHC17 and clathrin light chains (CLCs). CLCs bind in a 1:1 stoichiometric ratio with CHC17 and are known to be required for the endocytosis of some (but not all) cargo听to modulate the biophysical properties of clathrin (such as the ability of clathrin to deform membranes) and to mediate protein-protein interactions. However, the full scope of CLC functions remain to be defined. In particular, CLCs are encoded by two genes, which give rise to CLCa and CLCb, and tissue specific splice variants of these genes, resulting in a total of six听CLC isoforms.听CLCa and CLCb share about 60% identity, and each isoform and their tissue-specific distribution are conserved throughout mammalian species, suggesting that the CLC isoforms perform non-redundant, tissue specific roles. We are interested in understanding how diversity amongst the CLCs allows clathrin function to be fine-tuned to meet tissue-specific physiological needs.

To read more, take a look at the summaries of our most recent publications on CLCs

Selected Publications

CHC22 clathrin recruitment to the early secretory pathway requires two-site interaction with SNX5 and p115.听Greig J* and听Bates GT*, Yin DI, Briant K, Simonetti B,听Cullen PJ,听Brodsky FM. (2024)听The EMBO Journal. DOI:听.听*Equal contribution.

Clathrin light chains CLCa and CLCb have non-redundant roles in epithelial lumen formation.听Chen Y, Briant K,听Camus MD,听Brodsky FM.听(2023)听Life Sci Alliance 7听(1)听e202302175. DOI:

Clathrin and Clathrin-Mediated Membrane Traffic.听Bates GT, Briant K,听Bultitude WP,听Brodsky FM. (2023)听Encyclopedia of Cell Biology (Second Edition). DOI:听

Antagonistic regulation controls clathrin-mediated endocytosis: AP2 adaptor facilitation vs restraint from clathrin light chains.听Redlingsh枚fer L,听Brodsky FM. (2021)听Cells Dev. 25:203714.

Clathrin light chain diversity regulates membrane deformation听in vitro听and synaptic vesicle formation听in vivo.听Redlingsh枚fer L,听McLeod F,听Chen Y,听Camus MD,听Burden JJ,听Palomer E,听Briant K,听Dannhauser PN,听Salinas PC,听Brodsky FM.听(2020)听Proc Nat Acad Sci USA 117: 23527-23538

Clathrin鈥檚 life beyond 40: Connecting biochemistry with physiology and disease.听Briant K,听Redlingsh枚fer L,听Brodsky FM.听(2020)听Curr Opin Cell Biol听65:141-149.听

Building GLUT4 Vesicles: CHC22 Clathrin鈥檚 Human Touch.听Gould GW,听Brodsky FM,听Bryant NJ. (2020)听Trends Cell Biol听9:705-719.听

CHC22 clathrin mediates traffic from early secretory compartments for human GLUT4 pathway biogenesis.听Camus SM, Camus MD, Figueras-Novoa C, Boncompain G, Sadacca LA, Esk C, Bigot A, Gould GW, Kioumourtzoglou D, Perez F, Bryant NJ, Mukherjee S,听Brodsky FM. (2020)听J Cell Biol.听219(1).

Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism. Fumagalli M*,听Camus SM*,听Diekmann Y*,听Burke A,听Camus MD,听Norman PJ,听Joseph A,听Abi-Rached L,听Benazzo A, Rasteiro R,听Mathieson I,听Topf M,听Parham P,听Thomas MG,听Brodsky FM.听(2019)听eLife.听8:e41517. *Equal contribution.

Clathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension.听Biancospino M, Buel GR, Ni帽o CA, Maspero E, Scotto di Perrotolo R, Raimondi A, Redlingsh枚fer L, Weber J,听Brodsky FM*, Walters KJ*, Polo S*. (2019)听Nat Commun.听10(1):4974. *Co-corresponding authors.

CHC22 and CHC17 have distinct biochemical听properties and display differential regulation and function.听Dannhauser PN*, Camus SM*, Sakamoto K*, Sadacca LA, Torres JA, Camus MD, Briant K, Vassilopoulos S, Rothnie A, Smith CJ,听Brodsky FM. (2017)听J Biol Chem.听292:20834-20844. *Equal contribution.

Please follow this听 for a complete list of Prof. Brodsky's publications

Current Lab Members听

听

The Brodsky lab is an interdisciplinary team of talented cell biologists, geneticists, and biochemists.

Read more about our current lab members or about Frances Brodsky听

Positions Open

PhD Studentships

We currently have studentships available through the following PhD programmes:

Postdoctoral and Other Researchers

In the first instance, please send a CV and cover letter by听email to Professor Brodsky and lab manager Kit Briant, including the names of referees and their email contact information.

The availability of positions fluctuates with the funding situation, so we encourage applicants to apply for fellowship support.

A research background in any of the following disciplines would be appropriate for current projects in the lab:

• Molecular cell biology
• Structural biology
• Biochemistry
• Human genetics
• Mouse models

When formal job advertisements are made, they will be posted on the听.

Lab News

2024:

• Our latest work on CHC22 is out! in the EMBO journal about Josh and George's investigation on defining the molecular mechanism of CHC22 recruitment to the early secretory pathway.听
• We are sad to say goodbye to our two MSci students, Lucia Fernandez Barreiros and Letizia Filippi. It has been a great pleasure hosting you both, and we wish you the best of luck in the future!
• Welcome to our two new post-docs, Kamila Kamuda and Alyce McClellan. Kamila moves to our lab after completing her PhD at UCL, within David Lomas' lab and will use her extensive electron microsopy experience to structurally characterise the GLUT4 storage compartment. Alyce finished her PhD in the Raffan group at the University of Cambridge and will look to characterise the cellular changes in the GLUT4 trafficking pathway during the pathogenesis of Type 2 Diabetes. Read more about them and others lab members here.听

2023:

• We have published our latest work听on clathrin light chains!听听Using mice and 3D cell culture models, we investigated the differential and cooperative roles for the CLC isoforms (CLCa and CLCb) in epithelial lumen formation. Take a look at the full paper or our summary here!
• We are delighted to welcome two new MSci students to the lab - Lucia听Fernandez Barreiros and Letizia Filippi. Lucia will investigate the molecular basis for protein-protein interactions of CLCa and Letizia will characterise the biochemical properties of alternatively spliced variants of CHC17.听
• Check out in Nature as part of their Career Q&A series - she talks about her double life as a cell biologist and crime writer.听
• The Brodsky lab is well represented at this year's EMBO workshop in Venice on endocytosis (When biology of endocytosis meets physics: Emerging mechanisms and functions). Kit Briant听is presenting his latest work on novel CLCa interactors, and Frances is giving a talk on how clathrin subunit diversity enables tissue-specific membrane traffic.听
• Well done to our two summer research students, Iva听Organdjieva and Camille Davidson!听Iva was funded by a studentship from the Biochemical Society and investigated CLC interactors听at endosomes while Camille worked on understanding the mechanism of CHC22 uncoating. Both will return to 宅男视频 in October to continue their undergraduate studies. Good luck for the future!
• Congratulations to George Bates for defending听his PhD thesis! George has carried out some excellent work investigating molecular mechanisms regulating CHC22 clathrin function and will continue his research as a postdoc in the lab. Well done, George!
• We're sad to听say goodbye to Lauren Foltz, who has gone on to take on a role as an Analyst at EmPartners. During her time at the Brodsky lab, Lauren worked on developing physiological models to characterise GLUT4 trafficking听from听induced pluripotent stem cells. Best of luck, Lauren!

2022:

• We're excited to share ! Our study identifies a novel bipartite mechanism for CHC22 recruitment to the early secretory pathway听involving p115 and SNX5 (sorting nexin 5)
• It's been a busy year of conferences for the Brodsky lab, with George Bates presenting posters at听the BSCB (British Society for Cell Biology) conference at the University of Warwick with Josh Greig, at the Gordon Research Conference on听Lysosomes and Endocytosis in New Hampshire (USA) and at an听EMBO workshop on the听Endoplasmic Reticulum
• Goodbye to our postdoc听Will Bultitude! Will has worked on characterising the genetics of CHC17 and CHC22 since 2019 and has progressed to an editorial role at the听journal Scientific Reports. Best of luck in the future, Will!
• We have a new book chapter on "" in the Encyclopedia of Cell Biology, providing a听working knowledge for investigators in the field who encounter clathrin-mediated pathways in studies of associated physiology and disease.
• We're happy to announce that our former Master's student, Ivanna Yin, will join the lab as a new PhD student. Ivanna will work on further understanding the structural basis of clathrin assembly. Check out her profile here
• Farewell to lab technician Pallavi Ramsahye, who will go on to start a new role as听a higher scientific officer at the Institute of Cancer Research.听Good luck Pallavi!

2021:

• Welcome to our two new Master鈥檚 students, Ivanna Yin and Xinyi Zhang. Ivanna will work on the biochemistry of CHC22, and Xinyi will investigate the genetics of CHC17 and CHC22.
• Check out Lisa and Frances鈥� new reviewing the complementary roles of the AP2 adaptor complex and clathrin light chains in the regulation of clathrin-mediated endocytosis.
• Goodbye to our postdoc Yu Chen! Cherry has been with the lab since 2018 and has worked on characterising clathrin light chains in mouse models. She now takes up a position as a research scientist at Sanofi (Kymab).
• We鈥檙e happy to welcome our new lab technician, Pallavi Ramsahye!

2020

• Lisa鈥檚 paper has been published in PNAS!听听Lisa has been offered a position at the Max Planck Institute in Dresden 鈥� Congratulations and good luck in your new challenge!
• We鈥檙e delighted that our technician, Max, has been offered a PhD position at the University of Manchester to study metabolic engineering. Good luck Max!
• Another听听is out! 鈥淐lathrin鈥檚 Life beyond 40: Linking biochemistry to physiology and disease鈥� is published in Current Opinion in Cell Biology.
• Take a look at Frances鈥櫶�, now published in Trends in Cell biology.
• Congratulations to Hermione, who has completed her MSci! She鈥檚 off to do a PhD at the UCL Cancer Institute. Good luck!

2019

• Stephane鈥檚 paper has been published in听! Find out about how CHC22 functions in the early secretory pathway here. Good luck to Stephane and Marine in their new roles in Paris!
• Welcome to our new postdoc, Josh Greig! Check out our lab members听here.
• We have a new PhD student! George Bates joins on the Wellcome Trust structural, chemical and computation biology PhD programme and will investigate the biochemistry of CHC22.
• Congratulations to our Master's student, Carmen, who has been awarded an MRes! Good luck with your PhD at the Francis Crick Institute!
• We have a geneticist in the lab - Will Bultitude joins us from Anthony Nolan Research Institute to investigate clathrin polymorphisms!
• We have a new research technician in the lab. Welcome Max!
• Our CHC22 phylogenetics study has been published is听. Read news coverage in听,听听and听.
• We hosted the Workshop to Discuss the GLUT4 trafficking Map at Chicheley Hall with support from the UCL FMS domain. Thanks to all those who attended! The consensus map can be downloaded from听here.

2018

• We have posted a new听听on how the evolution of the gene encoding CHC22 reveals selection influencing CHC22's role in human glucose metabolism.听
• Welcome Yu Chen! Check out our听new postdoc.
• Join us in congratulating Dr Lisa Redlingshoefer who was awarded her PhD on "Clathrin light chains modulate the biophysical properties and function of clathrin".
• Check out our first听听ever!

2017

• Our lab published a new听听in JBC demonstrating how CHC17 and CHC22 have distinct biochemical properties and display differential regulation and function.
• Welcome Alice Burke, our new tech!
• Frances has been elected to the听听membership. Congrats!
• Frances speaks at the听:听"The two-edged sword of human glucose metabolism". Soapbox science is an outreach platform for promoting women in sciences.
• Frances gives the听15th Randall lecture听at King's College London: "Diversity of Clathrin Function in Membrane Traffic and Metabolism".
• The听Food, Metabolism and Society Research domain听website goes live! This group, created by Prof Brodsky, brings together researchers from across UCL and the Francis Crick Institute who work on diverse aspects of metabolic function and how metabolism and metabolic health impact society.

Older news:

2016

• Check out our new听听on the role of Clathrin Light Chains' in selective endocytosis and its influence on isotope switching.听
• We're happy to welcome a new post-doc: Kit Briant.听Check him out!
• Frances gives a听听at the University of York: "Diversity, Diabetes and Directing Traffic".

2015

• The Lab is growing. A new post-doc, Evelina Petitto, has joined our group!
• Frances has been elected to the听. This recognises her excellence in medical sciences. Congrats!
• UCSF says goodbye to Frances ! Check out the听听from her farewell party.

2014

• Frances accepts the position of听听at UCL.

2013

• Check out Frances's听听published in the Journal of Cell Biology. "So you think you know all about Clathrin?"

2012

• Check this out: the lab publishes a study on the role of Clathrin in centrosome integrity in the Journal of Cell Biology. The article was selected to be featured on the cover of the August edition of JCB (see on the right) and was also the听. This work was also featured in听.

2011

• Frances gives a lecture at the Karolinska Institute's for the Diabetes Day in 2011.

2000

• Frances co-founds the professional journal听Traffic.听, she and Mark Marsh reflect on how it all began.
• Frances says a little bit about her life since graduating from Harvard in an interview to the听.