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  Interactions of small G proteins with membranes


   Department of Biochemistry

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  Dr H Mott  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Department name: Department of Biochemistry, University of Cambridge
Supervisor: Dr Helen Mott

Our lab works on small G proteins of the Ras superfamily and their effector proteins. Most structural information on small G proteins has been obtained with protein that has been truncated at the C-terminus. However small G proteins of the Ras and Rho families are lipid modified and are peripheral membrane proteins but there is very little structural or biochemical information on these proteins in their membrane bound state. We are seeking to understand, at the molecular level, the structures and interactions of a number of small G proteins in the context of the membrane. We are using membrane mimics and NMR to probe the interactions between G proteins and the membrane and the effects of the membrane on binding to effector proteins and to GTPase activating proteins. All of the proteins that we work on are deregulated in cancer, and so the membrane interaction surfaces represent a new target interface for drug design. Our lab are also working on a number of peptidomimetics as a means of inhibiting small G proteins and this work may provide new possibilities for peptide design.

Taken together, our structural and biochemical analyses will further our understanding of the role of small G proteins in tumourigenesis or cell migration/metastasis and help in the design of therapeutics to inhibit their function.

Projects can be funded via the BBSRC DTP in Cambridge or the MRC DTP.
For the MRC - see Molecular and Cellular Project:
https://mrcdtp.medschl.cam.ac.uk/prospective-students/how-to-apply/available-projects-for-2018/
For BBSRC:
https://bbsrcdtp.lifesci.cam.ac.uk/
Overseas students can apply for funding via various scholarship schemes:
https://www.graduate.study.cam.ac.uk/finance/funding?ucam-ref=global-header

Funding Notes

UK nationals and EU students who meet the residency requirements can apply via the MRC or the BBSRC DTP. Further information about eligibility for funding can be found on the BBSRC website:
http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/

References

H.R. Mott & D. Owen (2015) Structures of Ras superfamily effector complexes: What have we learnt in two decades? Crit Rev Biochem Mol Biol. 50 85-133.

J.C. Thomas, J.M. Cooper, N.S. Clayton, C. Wang, M.A. White, C. Abell, D. Owen, H.R. Mott (2016) Inhibition of Ral GTPases using a stapled peptide approach. J Biol Chem. 291 18310-25.

J.R. Watson, H.M. Fox, D. Nietlispach, J.L. Gallop, D. Owen D, H.R. Mott (2016) Investigation of the Interaction between Cdc42 and Its Effector TOCA1: HANDOVER OF Cdc42 TO THE ACTIN REGULATOR N-WASP IS FACILITATED BY DIFFERENTIAL BINDING AFFINITIES. J Biol Chem. 291 13875-90

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