The molecular nature of mitochondrial proton leak (CRICHTON_U26DTP)

Mitochondria in our cells harness energy through the breakdown of nutrients to produce ATP through oxidative phosphorylation. However, they are not 100% efficient in this process largely due to proton leak pathways that occur, leading to energy lost as heat. In specialised brown adipose tissue, popularised as ‘good fat’, such heat production is specifically activated to protect against cold temperatures, where the associated calorie turnover can help maintain metabolic health. Though proton leak occurs in mitochondria from all tissues and has a major influence on overall energy metabolism. A better understanding of these processes could lead to health interventions in many areas. Obesity and related metabolic dysfuction are a primary health concern, affecting up to a third of the UK population and ~2 billion people globally.

This is an exciting and timely opportunity to help unravel the molecular processes of how proton leak occurs in mitochondria, taking advantage of advances that we have made in this area. The successful candidate will be trained in an array of biochemical and molecular biology techniques (e.g. cloning, recombinant membrane protein expression, purification and mutagenesis and liposome reconstitution, respirometic studies with isolated mitochondria), and biophysical methods to study protein dynamics, conformations and molecular interactions (e.g. analytical ultracentrifugation and differential scanning fluorometry). Supported by personal and professional development programmes, the post holder will gain a wealth of transferrable skills, which will be invaluable for scientific career progression.

The appointee will be supervised by Prof Paul Crichton (Norwich Medical School) at the Biomedical Research Centre, and Prof Tom Clarke (School of Biological Sciences), where they will benefit from stateof- art-facilities and an excellent research environment provided by UEA and surrounding Norwich Research Park. They will also gain valuable experience through exchange opportunities with the group’s collaborators (e.g. at the Wenner Gren Institute/University of Stockholm).