Insulin acts by binding to the transmembrane insulin receptor, triggering biochemical responses within target cells. Insulin resistance denotes reduced ability of insulin to lower blood glucose, and is associated with several major diseases. Image Vahid Aslanzadeh Insulin acts by binding to the transmembrane insulin receptor, triggering biochemical responses within target cells. Insulin resistance denotes reduced ability of insulin to lower blood glucose, and is associated with several major diseases. Some extreme forms of insulin resistance are caused by genetic mutations in the gene that encodes the receptor, INSR. The most severe of these disorders leads to uncontrollable diabetes and death in infancy, but many different mutations are found across the large receptor protein, and very few have been studied biochemically. In collaboration with the laboratory of Grzegorz Kudla (IGMM, Edinburgh) we are using genomics with synthetic and cell biology approaches to interrogate systematically the effect of mutations in the insulin binding domain on receptor expression, insulin binding and receptor signalling. Findings will be incorporated in a tool for the clinical community and will be of immediate translational value diagnostically. It will also inform future experimental medicine studies, and will allow rapid identification of mutations potentially amenable to novel targeted therapies. Related Researchers This work is being led by Dr Vahid Aslanzadeh, a postdoctoral researcher from Iran. He received his PhD in cell biology from the University of Edinburgh in 2017 conducting research on RNA processing. He also has hands-on experience with analysis of next-gen sequencing and large-scale genomics data, and served as a research fellow in bioinformatics at the University of Edinburgh before joining the Semple lab in November 2018. Funding Wellcome Trust This article was published on 2024-03-19
