PhD Studentship: Novel AM2 antagonists and the role of receptor interaction kinetics on in vivo eff

The project forms the part of a larger fully funded Wellcome trust discovery project currently underway within the group of Prof Tim Skerry and Dr Gareth Richards.

Pancreatic cancer is the 10th most common cancer, but in the next 15 years, it will become the second highest cause of cancer-related death. Unlike almost all other cancers, the prognosis has not changed in the last 30 years. After diagnosis, outcomes are very poor, with 1-year and 5-year survival rates of <25% and <5% respectively. The best current therapies offer only a few months of increased life expectancy, and patients’ quality of life is poor despite palliative treatments.

Adrenomedullin is a hormone involved in cancer growth and spread, which also has important roles in the control of blood pressure. Adrenomedullin acts through two different receptors one of which mostly regulates blood pressure. The other has important roles in cancer biology. We have shown that in model systems, blockade of the receptor reduces tumour growth and spread. We have developed novel lead compounds to block the adrenomedullin-2 receptor and inhibit its important roles in cancer, while keeping its normal functions.

The specific project aims to understand how these novel small molecules interact with their receptor (using Surface Plasmon Resonance) and how these difference effect the efficacy of these drug in models of pancreatic cancer.

Funding Notes

Wellcome trust/departmental studentship (stipend and fees included). Salary/stipend rate: RCUK recommended level £14,296 p.a

Entry Requirements
Candidates must have a first or upper second class honors degree or significant research experience. A good theoretical and practical knowledge of pharmacology, specifically in the area of GPCRS.
Interested candidates should in the first instance contact Dr Gareth Richards g.richards@sheffield.ac.uk

References
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select 'Oncology & Metabolism' as the department.
Proposed start date: 1st September 2017