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Hot fat - molecules to promote brown adipose tissue thermogenesis for better health (CRICHTONP_U23FMH)


   Norwich Medical School

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  Dr P Crichton  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

As well as conventional white fat that stores calories, it has recently been established that adult humans can also produce brown adipose tissue, which has the specialised ability to burn off calories for heat. The tissue contributes to energy metabolism and is activated to help protect mammals from cold temperatures. When stimulated in humans, the tissue can also help combat obesity and diabetes. Obesity and related conditions are a primary health concern in the UK and worldwide, affecting up to a third of the UK population and ~2 billion people globally.  

Energy expenditure by brown fat relies on the activation of Uncoupling Protein 1 (UCP1), a membrane protein that interrupts conventional nutrient breakdown for ATP production in mitochondria to instead generate heat. Our research has made key advances in clarifying how UCP1 functions and recently, we have established systems to identify molecules and drugs that directly interact to activate UCP1, opening up new therapeutic possibilities. This project will investigate the interaction of key activating compounds and drugs with UCP1, and relevant regulatory pathways of adipocyte thermogenesis, to clarify viable therapeutic strategies to encourage brown fat activity for better health.  

The successful candidate will be trained in an array of biochemical and molecular biology techniques to study isolated membrane protein (e.g. recombinant membrane protein production/purification, liposome assays and ligand-binding methodologies). They will also gain experience in mammalian cell culture methods (e.g. respirometric measurements, utilising genetic manipulations) to consolidate key findings on UCP1 regulation and energy metabolism. 

The post holder will gain a wealth of transferrable skills, supported by personal and professional development programmes, for scientific career progression. They will be supervised by Dr Paul Crichton at the Biomedical Research Centre (BMRC), a joint venture between the School of Biological Science and Norwich School of Medicine, where they will benefit from state-of-art-facilities and an exceptional research environment. They will also gain valuable experience through exchange opportunities through the group’s national and international collaborators.  

Entry requirements: at least UK equivalence Bachelors (Honours) 2:1 or UK equivalence Master’s degree; English language (Faculty of Science equivalent) - IELTS 6.5 overall, 6 in each category. 


Funding Notes

This PhD project is in a Faculty of Medicine and Health Sciences competition for funded studentships. These studentships are funded for 3 years and comprise UK fees, an annual stipend of £17,668 and £1,000 per annum for research training (RTSG). Overseas applicants (including EU) may apply but are required to fund the difference between Home and International tuition fees.

References


Cavalieri R, Hazebroek MK, Cotrim CA, Lee Y, Kunji ERS, Jastroch M, Keipert S, Crichton PG.
Activating ligands of Uncoupling protein 1 identified by rapid membrane protein thermostability shift analysis (2022) Mol Metab. 62:101526.
Crichton PG, Lee Y, Kunji ER. (2017) The molecular features of uncoupling protein 1
support a conventional mitochondrial carrier-like mechanism. Biochimie. 134:35-50.
Lee Y, Willers C, Kunji ER, Crichton PG. (2015) Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin. Proc Natl Acad Sci U S A. 112: 6973-8.
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