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York chemist awarded £1.8m from MRC

Posted on 21 August 2012

Marek Brzozowski, a chemist from York's Structural Biology laboratory has been awarded £1.8m to investigate interplay between diabetes and cancer.

Marek Brzozowski

This is an interdisciplinary and international programme that targets the key molecular contacts at the insulin receptor complex. The programme has a two-tier approach combining fundamental and applied research. In the very long term we consider that the research will be relevant to experimental and even clinical intervention of both metabolic and mitogenic (cancer-related) pathways.

Human insulin and Insulin-like Growth Factors I and II (IGF-I/II) are closely related protein hormones. They acquired separate biological functions, with insulin becoming a key metabolism controller, while IGF-I/II are major growth factors. When released in the blood the hormones bind, tightly and specifically, to their very homologous receptors, (Insulin Receptor (IR) and IGF-1R respectively).

Some Insulin IGFs analogues

Some Insulin IGFs analogues

All the analogues used in treatment of diabetes are still based on the inactive/storage forms of insulin that must be different than in complex with the receptor. Insulin and IGFs cross-bindings with their receptors imply insulin not only in metabolic regulation but also in cell proliferation and growth. As IGF-I/II are also cancer-specific growth factors the identification of pure 'metabolic' and 'cell growth' structural signatures of insulin and IGF-I/II has a fundamental importance not only for the understanding of the biology of these hormones, but also for new, effective treatments of diabetes and cancer.

This is a multidisciplinary programme that employes structural biology (YSBL-York, Walter and Eliza Hall Institute of Medical Research, Melbourne (WEHI)), cell signaling (University College Cork), organic and protein chemistry (Institute of Organic Chemistry and Biochemistry of Academy of Sciences, Prague (IOCB)).

One of the ‘side-effects’ of this Programme will be a web-based York Centre of Insulin Research that will accumulate and maintain all current and future structural data about insulin/IGFs systems. Their format will be easily accessible for public, students and medical professionals invigorating progress towards more efficient treatment of these diseases.