‘Molecules to Modulate Insulin Production?' (360G-Wellcome-204515_Z_16_Z)

The Pathfinder project led by Dr Zoë Waller at University of East Anglia aims to investigate the biological properties of molecules with the potential to alter insulin gene expression. Over 400 million people worldwide are diagnosed with diabetes, a major cause of blindness, kidney failure, heart attacks, stroke and lower-limb amputation. Despite current treatments, the WHO projects that diabetes will be the 7th leading cause of death in 2030, thus there is the need for alternative treatment options. The insulin minisatellite region resides in the promoter of the gene coding for insulin, which regulates how the gene is read. The region consists of a tandem repeat DNA sequence capable of forming alternative DNA secondary structures. Mutations or shortening in the length within this sequence have been linked to the development of both type-1 (insulin dependent) and type-2 (noninsulin-dependent) diabetes. We predict we can alter insulin expression specifically by targeting this region. We have identified hit compounds which can target this DNA. This project will explore the biological capabilities of these molecules, their effects on insulin gene expression in cells and determine any potential liabilities for future therapeutic development. The potential impact of this could provide alternative treatment options for diabetes.