PhD Studentship in York Structural Biology Laboratory, Dept. of Chemistry, University of York: Molecular and structural studies on insulin: Insulin Receptor interactions

Insulin - Insulin Receptor (IR) interactions are at the centre of insulin-driven control of human metabolism. Disruption of insulin secretion, actions, or both, leads to severe metabolic syndrome of which diabetes type 1 (insulin-dependent) and type 2 (non-insulin dependent) are the main manifestations. Therefore a detailed 3-D description of insulin:IR coupling is paramount for understanding IR-mediated signal transduction and initiation of insulin signalling enabling structure based approaches towards improved pharmacological therapies. The first insight into the effective insulin:IR molecular engagement was achieved, but a complete picture of Insulin-receptor interactions remains elusive.

The main aims of this project are: (a) search for workable insulin:IR molecular platform by design, optimization and efficient scale up of production of various fragments of IR ectodomain for structural work, (b) expansion of current low-resolution (~3-4 Å) X-ray structural studies of insulin-IR complexes towards detail atomic definition of insulin:IR interface, and, ultimately, elucidation of the molecular bases of the complete engagement of insulin with IR.

The project is sponsored by the Guy Dodson memorial fund, and is run in York (York Structural Biology Laboratory, Dept. of Chemistry, University of York) in close collaboration with Novo Nordisk. The student will have access to unique insulin know-how and in-house methodologies of Novo Nordisk, together with the possibility to perform part of the research in their laboratories. This project is for 4 years starting as early as possible in 2016 (by the 1st October 2016).

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. Shortlisted applicants will be invited for an interview with Professor Brzozowski (marek.brzozowski@york.ac.ukmailto:marek.brzozowski@york.ac.uk) following the closing date.

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students

Funding Notes

This project is fully funded for 4 years by the Guy Dodson Fund for Structural Biology research at York, established in 2013 with a donation from Danish pharmaceutical company, Novo Nordisk. Funding will cover (i) tuition fees at the UK/EU rate, (ii) a tax-free annual stipend at the standard Research Council rate (£14,057 for 2015-2016, typically increases annually in line with inflation) and (iii) a contribution towards research costs. Applications are welcomed from those from the UK and other EU countries.

For more contact info see:

http://www.york.ac.uk/media/chemistry/postgraduatestudy/phdvacancies/2016ent...

References

Menting et al. How insulin engages its primary binding site on the insulin receptor. (2013) Nature, 493, 241-245 Jiracek et al. Implications for the active form of human insulin based on structural convergence of highly active hormone analogues. (2010) PNAS, 107, 1966-1970

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Gerd Schluckebier Director Protein Structure

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