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MRC DiMeN Doctoral Training Partnership: Precision Diabetic Medicine: Using the metabolome to optimize exercise as a therapeutic strategy in the ageing diabetes patient


MRC DiMeN Doctoral Training Partnership

, Dr Daniel West Wednesday, January 27, 2021 Competition Funded PhD Project (Students Worldwide)
Leeds United Kingdom Analytical Chemistry Biochemistry Cardiology Data Science Endocrinology Physiology

About the Project

Type 1 diabetes (T1D), is a chronic condition in which the pancreas produces little or no insulin. Insulin is a hormone needed to allow glucose to enter cells as a source of energy. The loss of insulin means that people with T1D cannot regulate their blood glucose levels.

Globally, over 1.1 million people between the ages of 0-19 have Type 1 Diabetes (T1D) and the incidence of T1D is growing 3% annually. 

Exercise provides health benefits for individuals with T1D, reducing cardiovascular disease (CVD) and frailty risk, and increasing physical fitness. However, the metabolic response to exercise can be disrupted in T1D patients leading to impaired blood glucose regulation. This response is difficult to manage and contributes to lower physical activity levels within the T1D population. This decrease in physical activity is acutely observed in older individuals with T1D (who exhibit accelerated ageing) and may contribute to greater incidences of frailty and CVD in the T1D population. Moreover, patients with T1D have a high variability in blood glucose response to exercise between individuals. The variability in metabolic response to exercise is unexplained, poorly classified, and cannot be predicted. With an ageing global T1D population, overcoming barriers to exercise will be an invaluable tool to prevent frailty, CVD and associated healthcare and economic burdens in the T1D population.  

The study will collect samples from human exercise intervention studies in a T1D clinical population within a dedicated clinical exercise facility at the University of Newcastle under the supervision of Dr Daniel West(https://www.ncl.ac.uk/hnrc/staff/profile/danielwest.html#background ). This project will then take an omic precision medicine approach at the University of Leeds under the supervision of Dr Lee Roberts(https://medicinehealth.leeds.ac.uk/medicine/staff/713/dr-lee-roberts https://twitter.com/Roberts_Lab). State-of-the-art metabolomic and lipidomic mass spectrometry techniques will be used to analyse the metabolic response to exercise in blood plasma of individuals with T1D. This data will be used to characterise, classify and predict the large differences between individuals blood glucose response to exercise in ageing patients with T1D. Metabolomic/lipidomic modelling of this data will be used to characterise the metabolic markers of exercise in younger and older T1D patients, define the differences in blood glucose control and to identify baseline metabolic markers that may predict impaired response to exercise. This approach provides molecular insights into the pathological response to exercise observed in some individuals with T1D.

This project will suit a student with a background in biochemistry, physiology, clinical sciences, exercise sciences or analytical chemistry with an interest in, or experience of, mass spectrometry, metabolomics, lipidomics, metabolism, exercise, diabetes, metabolic disease or physiology. It provides training in clinical exercise studies and cutting-edge metabolic and lipidomic mass spectrometry profiling in a translational application to metabolic disease. 

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A 


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3.5yrs. Funding will cover UK tuition fees and stipend only. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021
Good luck!

References

Lee D Roberts, Pontus Boström, John F O'Sullivan, Robert T Schinzel, Gregory D Lewis, Andre Dejam, Youn-Kyoung Lee, Melinda J Palma, Sondra Calhoun, Anastasia Georgiadi, Ming-Huei Chen, Vasan S Ramachandran, Martin G Larson, Claude Bouchard, Tuomo Rankinen, Amanda L Souza, Clary B Clish, Thomas J Wang, Jennifer L Estall, Alexander A Soukas, Chad A Cowan, Bruce M Spiegelman, Robert E Gerszten (2014) β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab. 19(1):96-108. doi: 10.1016/j.cmet.2013.12.003. https://pubmed.ncbi.nlm.nih.gov/24411942/
Lee D Roberts, Tom Ashmore, Ben D McNally, Steven A Murfitt, Bernadette O Fernandez, Martin Feelisch, Ross Lindsay, Mario Siervo, Elizabeth A Williams, Andrew J Murray, Julian L Griffin (2017) Inorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Release. Diabetes; 66(3):674-68. doi: 10.2337/db16-0843. https://pubmed.ncbi.nlm.nih.gov/28028076/
Guy S Taylor, Kieran Smith, Tess E Capper, Jadine H Scragg, Ayat Bashir, Anneliese Flatt, Emma J Stevenson, Timothy J McDonald, Richard A Oram, James A Shaw, Daniel J West (2020) Postexercise Glycemic Control in Type 1 Diabetes Is Associated With Residual β-Cell Function. Diabetes Care 43(10):2362-2370. doi: 10.2337/dc20-0300. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510016/

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