Massively Parallel Interrogation of Insulin Receptor Function to Accelerate Diagnosis and Facilitate Translational Research

Insulin’s actions on the body are exerted by binding to a unique insulin receptor (INSR), a dimeric member of the receptor tyrosine kinase class of growth factor receptors. INSR is thus crucial in determining insulin sensitivity. In rare people genetic mutations damage the INSR leading to severe insulin resistance that may be fatal in infancy.

Many new, different alterations in the INSR are still being discovered, but it is often difficult for diagnostic labs to determine which are disease causing, especially in minority ethnic groups.

INSR changes are also found in the general population, but whether they are important for risk of conditions such as T2D is not well studied.

The host labs recently developed an approach to studying the function of >15,000 alterations in the extracellular domain of the receptor simultaneously.

In this project the same pipeline will be applied to the intracellular domain of the receptor, with additional studies of new aspects of receptor function relevant to disease.

This will provide outstanding training in molecular biology, insulin signalling, and computation, and will generate a freely available resource of huge value to doctors and scientists focused on improving treatment of insulin resistance and understanding the mechanism of insulin’s action.