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LMCB - Laboratory for Molecular Cell Biology

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Chris Stefan's picture
LMCB Group Leader, UCL Associate Professor
 

c.stefan@ucl.ac.uk
+44 (0)20 7679 7208
LMCB Room 3.01


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Organelle cross talk and membrane dynamics

Research synopsis

Cell growth and integrity require membrane growth and integrity. We are using cross-disciplinary approaches to elucidate vital roles of inter-organelle contacts in membrane biogenesis and homeostasis at the molecular, ultra-structural, cellular, and tissue levels. Inter-organelle contacts serve as key sites for the coordinated regulation of membrane lipid metabolism and transport. Our studies have focused on contacts between the endoplasmic reticulum and the plasma membrane (ER-PM contacts), providing new understanding of membrane lipid and calcium dynamics during regulated exocytosis and polarised secretion. We are currently examining ER-PM contact architecture and function in hepatocytes, polarised epithelial cells of the liver. These investigations are suggesting new strategies to control biliary secretion that may prove beneficial in the treatment of liver disease. 

Furthermore, we are probing how alterations in inter-organelle contacts and membrane lipid homeostasis result in organelle damage. These studies are revealing novel protective pathways that sense and respond to membrane stress conditions to ensure membrane integrity and organelle homeostasis. Numerous diseases are caused by imbalances in membrane lipid homeostasis including cancer, diabetes, and neurodegenerative disorders. We expect our investigations will identify new targets and strategies for the treatment of diseases caused by disruptions in membrane lipid and organelle homeostasis. 

Stefan lab research imageStefan lab research image

Selected publications

Gomes Castro et al. (2022). Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution. eLife. DOI: https://elifesciences.org/articles/74602
Thomas et al. (2022). Tricalbin proteins regulate plasma membrane phospholipid homeostasis. Life Sci Alliance. 5(8):e202201430. DOI: 10.26508/lsa.202201430
Omnus D, et al (2020). A Heat Sensitive Osh Protein Controls PI4P Polarity. BMC Biology. 18:28. DOI: 10.1186/s12915-020-0758-x
Collodo D, et al (2019). Tricalbins Control ER Curvature to Maintain PM Integrity. Developmental Cell. 18: 476-487.e7. DOI: 10.1016/j.molcel.2019.06.037
Nishimura T, et al (2019). Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis. Molecular Cell, 75: 1043-1057. DOI: 10.1016/j.molcel.2019.06.037
 

 

 

Funders

Medical Research Council

Research themes

Membrane organisation
Organelle homeostasis
 

Technology

Electron microscopy
Super-resolution microscopy
Optical biology and spectroscopy
Quantitative lipidomics and proteomics
Bioinformatics and computational modelling
Translational research
 

People

Matthew Bentham (Research Fellow)
Gary Chung (Research Fellow)
Ffion Thomas (PhD Student)
Bailey Hewlett (PhD Student)
Francesca Montesi (MSci student)
Cyril Lemerle (MSci student)

Collaborators

Jemima Burden (LMCB, UK)
Robin Ketteler (LMCB, UK)
Franck Pichaud (LMCB, UK)
Kenneth Linton (QMUL, UK)
Tamir Rashid (Imperial, UK)
Paul Gissen (ICH, UK)
Sara Mole (ICH, UK)
Emily Eden (UCL IoO, UK)
Frances Brodsky (UCL BioSci, UK)
Tim Bartels (UCL/UKDRI, UK)
Sonia Gandhi (UCL/FCI, UK)
Andela Saric (IST, Austria)
Robbie Loewith (Univ Geneva, Switzerland
Christian Ungermann (Osnabruck Univ, Germany)
David Teis (Innsbruck Med Sch, Austria)
Ruben Busnadiego-Fernandez (Univ Med Gottingen, Germany)
Roberto Covino (Frankfurt Inst Adv Studies, Germany)
Nozomu Kono (Tokyo Univ, Japan)
Maya Schuldiner (Weizmann Inst, Israel)