THE ROLE OF RAMPS IN LIGAND-ENGENDERED SIGNAL BIAS OF SECRETIN-LIKE RECEPTORS

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The research that we propose will have a broad range of impacts from advancement of fundamental scientific knowledge to training of a highly skilled workforce.

Advancement of scientific knowledge: Our research program will develop knowledge that will enhance our understanding of GPCR pharmacology. The secretin family GPCRs are important therapeutic targets for a host of disorders including diabetes, obesity, cardiovascular disease, neurodegenerative disorders. The incretins (GLP-1, glucagon and GIP) form a significant proportion of the secretin receptor family. These molecules have been targeted for treatments related to diabetes and obesity. To date, incretin-based therapeutics generates in excess of $1 billion annually and consequently, there is considerable interest in developing the next generation of diabetic drugs. Our investigations into RAMP association with secretin receptors will aid this research. Any novel biological data generated will yield new knowledge that will be disseminated through international journals, conference publications, seminars, collaborative contacts with other researchers and participation in professional body events.

Pharmaceutical and Biotechnology industries: The UK economy relies heavily on the Pharmaceutical and Biotechnology industry; it employs more than 250,000 people and generates billions of pounds annually. Drug discovery relies extensively on a strong basic-science background to provide insights into potential drug targets and the development of new assays and technologies. Our work, systematically analysing one entire family of GPCRs, will contribute to this knowledge base and is backed by industry. Our data will eventually aid in the design of more efficacious and effective drugs targeting the secretin receptor family. This will be highly relevant not only to "big pharma", but also to regional businesses in the Midlands.

Translational medicine: Our work has the potential to contribute to significantly improved efficacy and reduced treatment costs for diseases associated with many GPCR-based diseases. Thus our work is likely to impact positively on the economics of the health care sector over the longer-term.

Provision of skilled workforce: The PDRA (Dr Weston) and the research technician working on this project will be trained in a wide range of pharmacology techniques. These skills are highly specialised and valuable, and will equip them for careers in academia or industry. Dr Weston will be encourage to attend courses held at the University of Warwick's Centre for Lifelong Learning provides a range of courses to further aid members of staff in their professional development. Dr Weston will be encourage to attend these courses and also to enrol on the Postgraduate Certificate in Academic and Professional Practice (PCAPP). Further, Warwick and Aston provide a range of transferable skills courses designed to maximise individual potential and employability. Thus our work will contribute to the economic competitiveness of the UK through the provision of highly skilled labour.

The general public: We will disseminate our findings to the general public at the earliest juncture. WMS has an active public engagement policy and an excellent track record in outreach activities. We will host yearly public lectures for local secondary school teachers from around the Midlands at WMS. These events will be aimed at enthusing school children from aged 11-13 in the "Science of Cells". Public lectures on the importance and implications of our science will be given through Café de Scientifique a forum for debating science issues, promoting public engagement and making science accountable. Articles will also be produced for community newsletters. We will also develop a project webpage and podcasts aimed specifically at the lay audience to explain our science and its medical benefits.