Objective Type 2 diabetes mellitus, one of the major healthcare challenges of our time, is characterized by failure of beta cells to functionally adapt to increased peripheral insulin resistance. The resulting chronic elevations in blood glucose concentration are associated with heart, kidney, liver, nerve and retinal disease, as well as cancer. Here, by combining novel optogenetic, photopharmacological and innovative imaging approaches, we aim to unravel the complexity underlying the multicellular regulation of insulin secretion from islets of Langerhans during health and disease. In particular, we will examine a role for privileged pacemakers/hubs in orchestrating population responses to stimuli, identify what makes these specialized cells unique at the RNA/protein level, and understand how they contribute to islet development and failure. Furthermore, we will address whether the intraislet regulation of insulin secretion operates in vivo to determine glucose homeostasis, focusing on the neural-endocrine interface. Lastly, the mechanisms underlying islet cross-talk will be investigated directly in situ within the pancreas of living mice, paying close attention to the roles of the vasculature and secreted factors. As such, these studies should unveil a new route for restoration of insulin secretion in man, as well as provide the foundation for the de novo construction of islets for transplantation. Fields of science medical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesclinical medicinetransplantationmedical and health scienceshealth sciencesnutritionobesity Keywords type 2 diabetes beta cell islet Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-STG - ERC Starting Grant Call for proposal ERC-2016-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution THE UNIVERSITY OF BIRMINGHAM Net EU contribution € 1 681 468,00 Address Edgbaston B15 2TT Birmingham United Kingdom See on map Region West Midlands (England) West Midlands Birmingham Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 681 468,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE UNIVERSITY OF BIRMINGHAM United Kingdom Net EU contribution € 1 681 468,00 Address Edgbaston B15 2TT Birmingham See on map Region West Midlands (England) West Midlands Birmingham Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 681 468,00