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Dr Ben Nichols

Research Interests

Cell biology of the plasma membrane

The plasma membrane provides the key interface between a cell and its environment, and thus has a central role in a very wide range of cell processes.

We are interested in the mechanisms underlying several important aspects of plasma membrane cell biology: particularly, how regions of the membrane are specialised for different functions, and how proteins and lipids are internalised from the membrane. We focus on the role of oligomeric protein assemblies that form specific microdomains. Caveolae, flask-shaped membrane invaginations formed by cavin and caveolin proteins, constitute one kind of microdomain, and flotillin proteins form another. Achievements over the last five years have included revealing functions for flotillin proteins in cell migration, determining key protein actors at the neck of caveolae, characterising the large 80S protein complex that generates the bulb of caveolae, and quantifying flux through different endocytic pathways in tissue culture cells.

Studies in cultured cells and model organisms have been successful in identifying many molecular components and specific protein-protein interactions. We now want to confront the complexity of how these components function in differentiated cell types. Our interests in caveolae and in endocytosis lead to projected experiments to elucidate the function of caveolae in the vascular system, and the membrane traffic mechanisms underlying vesicular transcytosis in endothelium. We will complement these experiments with biochemical and functional analysis of protein complexes at the neck of caveolae. In the case of flotillins, we now know that these proteins have an important role in sphingosine-1-phosphate signalling, and projected experiments will determine both the relevant mechanisms and links to regulation of endocytosis.

Key Publications

Full list of publications can be seen on PubMed.

Cells respond to deletion of CAV1 by increasing synthesis of extracellular matrix. Mendoza-Topaz C, Nelson G, Howard G, Hafner S, Rademacher P, Frick M, Nichols BJ. PLoS One. 2018 Oct 22;13(10):e0205306

Vesicular trafficking plays a role in centriole disengagement and duplication. Xie S, Reinecke JB, Farmer T, Bahl K, Yeow I, Nichols BJ, McLamarrah TA, Naslavsky N, Rogers GC, Caplan S. Mol Biol Cell. 2018 Sep 6:mbcE18040241.

Flotillin proteins recruit sphingosine to membranes and maintain cellular sphingosine-1-phosphate levels. Riento K, Zhang Q, Clark J, Begum F, Stephens E, Wakelam MJ, Nichols BJ. PLoS One. 2018 May 22;13(5):e0197401.

Flotillin-1 interacts with the serotonin transporter and modulates chronic corticosterone response. Reisinger SN, Kong E, Molz B, Humberg T, Sideromenos S, Cicvaric A, Steinkellner T, Yang JW, Cabatic M, Monje FJ, Sitte HH, Nichols BJ, Pollak DD. Genes Brain Behav. 2018 Apr 18:e12482.

EHD Proteins Cooperate to Generate Caveolar Clusters and to Maintain Caveolae during Repeated Mechanical Stress. Yeow I, Howard G, Chadwick J, Mendoza-Topaz C, Hansen CG, Nichols BJ, Shvets E. Curr Biol. 2017 Oct 9;27(19):2951-2962.e5.

Caveolae protect endothelial cells from membrane rupture during increased cardiac output. Cheng JP, Mendoza-Topaz C, Howard G, Chadwick J, Shvets E, Cowburn AS, Dunmore BJ, Crosby A, Morrell NW, Nichols BJ. J Cell Biol. 2015 Oct 12;211(1):53-61.

Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids. Shvets E, Bitsikas V, Howard G, Hansen CG, Nichols BJ. Nat Commun. 2015 Apr 21;6:6867.

 

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