Advancing diabetes, obesity and metabolic disease treatment in the post-genomic era
The Clore Laboratory is an internationally recognised research centre for diabetes, obesity and metabolic disease. It acts as a Contract Research Organisation providing added-value pre-clinical services to pharmaceutical and biotechnology companies from target discovery and validation, through lead generation and optimisation, to proofof- concept and selection of clinical candidate. In addition to its contract research programmes, the Clore Laboratory scientists undertake in-house research programmes to identify and evaluate novel drug targets.
The Laboratory is led by Mike Cawthorne and Jon Arch. Both have proven track records in drug discovery at SmithKline Beecham. Mike led the team that first recognised the potential of insulin sensitising drugs and then identified and developed rosiglitazone (Avandia), which now has multi-billion dollar sales. Jon pioneered research on thermogenic drugs and orexins antagonists as anti-obesity treatments. Both Mike and Jon have more than 100 peer-reviewed publications. Clients benefit from their know-how in the design of studies.
Staff at the Clore Laboratory have expertise in molecular genetics, biochemistry, pharmacology, nutrition and the physiology of metabolic disease. Discovery services from early target validation using molecular biology, immuno and in situ histochemical techniques and phenotyping of genetically modified rodents, through to proofof- concept and clinical candidate selection studies as well as evaluation of in-licensing opportunities are available.
Protocols can include measurements of food intake, energy expenditure by indirect calorimetry, body composition by DEXA scanning, and physiological measurements, such as glucose tolerance, euglycaemic hyperinsulinaemic clamp, insulin secretion and blood pressure. Circulating concentrations of metabolites, hormones and enzymes can be measured on microsamples. Metabolite concentrations, enzyme activities and mRNA concentrations can be measured in tissue samples, and the tissues processed for immunohistochemical or in situ hybridisation with quantitative image analysis. We have particular experience with pancreatic islets and skin. We can quantify ?-cell mass, which is crucial to the development of new therapies aimed at islet cell remodelling in type 2 diabetic patients.
We are using unique model systems together with microarray expression and suppression subtractive hybridisation to identify candidate genes associated with regulation of energy balance, insulin sensitivity and pancreatic ?-cell function. We are particularly interested in metabolic programming in early life and have shown that treatment of mothers during pregnancy and lactation with leptin re-programmes the offspring so that they are protected from the adverse effects of high-fat diet feeding throughout their lives. This unique model is a likely source of molecular targets for future drugs and is available as a joint-venture project.
It is estimated that there will be more than 300 million diabetics in the world by 2025 and the number with obesity will be well over a billion. Much of this increase will occur in developing countries where many subjects will be unwilling to use or unable to afford ?Western? medicine. Consequently, there is a need to identify natural products with appropriate actions and validate their use. The Clore Laboratory has a history of collaboration on such projects, including studies to identify active principles and mechanisms of action.
The Clore Laboratory provides an excellent training ground in laboratory research. Students benefit from an integrated biology approach, and their DPhil degrees are highly rated by research groups including industry worldwide. In addition to the laboratory-based projects, taught MSc programmes in the Molecular Basis of Metabolic Disease and Drug Discovery and Development are also available. These programmes provide leadingedge knowledge delivered by both academic and industry experts.
A research degree and taught MSc programme in Bioinformatics are also available. The ability to efficiently manage and integrate the current wealth of data requires a combination of computational methodologies and biological understanding. The taught MSc course provides intensive training in software development, database technologies and molecular genetics and is suitable for graduates with both biological and non-biological backgrounds.
Diabetic and non-diabetic skin
These courses are open to both EU and international students. Details of fees are available at www.buckingham.ac.uk/clore/postgraduate. The University offers a pleasant garden campus in a market town within easy reach of Oxford and the lively Milton Keynes. It has 450 places available in on-campus halls of residence with free wireless network internet access, car parking and CCTV for added security.
For more information, contact:
Professor Mike Cawthorne
University of Buckingham
Buckingham MK18 1EG
Tel: +44 (0)1280 820309