Wellcome Trust Discovery Grant to advance therapies for metabolic disorders

Imperial led research to help develop therapeutic strategies for type 2 diabetes, obesity, and related metabolic disorders, receives over £6m.

Dr Alejandra Tomas, a Senior Lecturer in the Department of Metabolism, Digestion and Reproduction, alongside a team of distinguished researchers, has been awarded a significant Wellcome Trust Discovery Grant for their research project, titled "Allosteric modulation of class B1 GPCRs via cholesterol binding sites". The grant, totalling £6,821,221 and spanning eight years, aims to propel groundbreaking research in the field of G protein-coupled receptors (GPCRs) and their role in metabolic disorders.

The project, led by Dr. Tomas, brings together a consortium of experts from seven labs across different institutions. Collaborators include co-investigators Ben Jones, Sarah Rouse, Emma McGlone, Jorge Bernardino de la Serna and Ed Tate from Imperial College London, and Christian Siebold from Oxford. With a team of postdoctoral researchers, research associates, and PhD students, the project will delve into unexplored areas of GPCR biology. 

The core objective of the study is to unravel the intricate mechanisms underlying cholesterol binding sites within class B1 GPCRs, with a specific focus on GLP-1R and GCGR receptors. Through a combination of cutting-edge methodologies, ranging from computational simulations to in vivo models utilising human stem cell-derived pancreatic islets and humanised receptor mouse models, the research aims to better understand the functional significance of these binding sites.

Regarding the potential significance of the research, Dr Tomas said: "This study will generate the fundamental knowledge necessary to target cholesterol binding sites within GPCRs, paving the way for the development of innovative therapeutic strategies for type 2 diabetes, obesity, and related metabolic disorders."

This project's outcomes are anticipated to advance our understanding of GPCR biology and lay the groundwork for future structure-based drug design initiatives. By leveraging actionable insights from receptor-lipid interactions, the research aims to catalyse the development of novel and improved therapies, addressing pressing global health challenges around metabolic disorders.