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, and – to some extent – growth and life-span regulation as well. 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. High similarity of insulin to Insulin-like Growth Factors (IGF-I and II) and IR to IGF-1R results in some overlaps of insulin’s metabolic and IGFs’ mitogenic signaling pathways. Therefore a detailed 3-D description of insulin:IR coupling is paramount for understanding IR-mediated signal transduction and initiation of insulin signaling. The first insight into effective insulin:IR molecular engagement was achieved early this year, but formidable challenges of expression of IR fragments and low resolution of insulin:IR complexes inhibit further progress in this field.

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 (ca. 4 A) X-ray structural studies of insulin-IR complexes towards detail atomic definition of insulin:IR interface.

In additionl to the project specific training, all research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills

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