About the Project
What don’t we understand? Following binding to extracellular matrix ligands, adhesion receptors trigger the assembly of multi-protein complexes on the cytoplasmic face of the plasma membrane. These complexes contain signalling molecules and cytoskeletal proteins, and their role is to control the location of signalling pathways and provide a physical link to the contractile actomyosin polymer network. The identity of the molecules that transduce signals, the mechanisms of complex assembly and disassembly, the stoichiometry of complex components, the key control points, and the extent of variation between complexes in different cells are not known.
How to get answers to these questions? Recently, we have developed the first methodologies for employing mass spectrometric analyses (both proteins and phosphoproteins) of isolated adhesion complexes to define the adhesion receptor-associated proteome. These techniques allow an unbiased approach to studying adhesion signalling. This project will therefore explore one of the following areas: (a) the identity of the links between adhesion receptors and the cell cycle machinery that are responsible for cell rounding during mitosis, (b) the cell cycle-dependent changes that take place in adhesion complexes [both using proteomic, bioinformatic, biochemical (e.g. IP-blotting and phosphorylation analysis) and/or cell biological approaches (e.g. fluorescence imaging)], and (c) the mechanisms whereby extracellular matrix rigidity is converted into signals that control cell proliferation and tumour evolution. Candidates will then be validated by a combination of biochemical (e.g. using IP-blotting and phosphorylation analysis) and/or cell biological approaches (e.g. using fluorescence imaging).
Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in biological sciences, such as biochemistry and molecular biology. A Masters qualification in a similar area would be a significant advantage.
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
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4. Horton, E.R., Byron, A., Askari, J.A., Ng, D.H.J., Millon-Frémillon, A., Robertson, J., Koper, E.J., Paul, N.R., Warwood, S., Knight, D., Humphries, J.D. and Humphries, M.J. (2015) Definition of a consensus integrin adhesome and analysis of its dynamics during adhesion complex assembly and disassembly. Nature Cell Biol. 17: 1577-1587
5. Horton, E.R., Humphries, J.D., Stutchbury, B., Jacquemet, G., Ballestrem, C., Barry, S.T. and Humphries, M.J. (2016) Modulation of FAK and Src adhesion signalling occurs independently of adhesion complex composition. J. Cell Biol. 212: 349-364
6. Jones, M.C., Askari, J.A., Humphries, J.D. and Humphries, M.J. (2018) Cell adhesion is regulated by CDK1 during the cell cycle. J. Cell Biol. 217: 3203-3218
7. Lock, J.G., Jones, M.C., Askari, J.A., Gong, X., Oddone, A., Olofsson, H., Göransson, S., Lakadamyali, M., Humphries, M.J. and Strömblad, S. (2018) Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis. Nature Cell Biol. 20: 1290-1302
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