The metabolite interactions of mitochondrial Uncoupling Protein-1 in regulating brown fat energy expenditure

CRICHTON_U22DTP

This is an exciting and timely opportunity to study Uncoupling Protein 1 (UCP1), the mitochondrial membrane protein that allows brown adipose tissue, popularised as ‘good fat’, to burn off calories as heat. The protein helps mammals fight cold temperatures, and can contribute to energy expenditure in humans to maintain metabolic health.

The molecular processes on how UCP1 is activated is not well understood. This project will focus on determining novel ligand interactions of UCP1 with various metabolites that potentially act to regulate the protein, taking advantage of recent advances that we have made on the molecular nature of UCP1. The successful candidate will be trained in an array of biochemical and molecular biology techniques to study isolated membrane protein (e.g. cloning, recombinant protein expression, membrane protein purification, liposome reconstitution assays, protein conformation analysis and novel ligand-binding thermostability shift assessment methods). The project will also include methods to assess UCP1 activity in cultured mammalian cells (e.g. respirometric measurements, genetic manipulations) to consolidate key findings on UCP1 regulation and energy metabolism. 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 Dr Paul Crichton at the Biomedical Research Centre (BMRC), where they will benefit from state-of-art-facilities and an excellent research environment provided by Norwich Medical School and the School of Biological Sciences, as well the surrounding Norwich Research Park. They will also gain a wealth of valuable experience through exchange opportunities with the group’s national and international collaborators (e.g. the Jastroch group, Wenner Gren Institute/University of Stockholm).

References 

Crichton PG, Lee Y, Kunji. ER The molecular features of uncoupling protein 1 support a conventional mitochondrial carrier-like mechanism (2017) Biochimie 134:35-50.

Lee Y, Willers C, Kunji ER, Crichton PG. Uncoupling protein-1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin (2015) Proc Natl Acad Sci USA 112: 6973-8

Ruprecht JJ, King MS, Zögg T, Aleksandrova AA, Pardon E, Crichton PG, Steyaert J, Kunji ERS. The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier (2019) Cell 176(3):435-447.e15.