About the Project
Exercise is a key biological process. Exercise training leads to whole body adaptations that improve fitness, prevent frailty, and offer protection against age-related dysfunction and disease. Skeletal muscle is an important tissue governing the whole body adaptive response to exercise training. However, the molecular mechanisms through which muscle adapts to exercise, and signals to other tissues and organs to induce health benefits, is poorly understood. Signals released from muscle which communicate to other organs and tissues have been termed myokines. This project will investigate the role of a secretory protein and a metabolite as potential exercise-mediated myokines regulating multiple organ (muscle, liver, adipose tissue) and whole body adaptation to exercise. The project will use state-of-the-art metabolic and physiological phenotyping techniques such as indirect calorimetry, high-resolution mitochondrial respirometry and metabolomics alongside in vivo imaging techniques such as PET/CT to probe the effects of the protein and metabolite myokines on exercise and metabolism using transgenic and exercise animal models. The successful candidate would also receive training in biochemical, and cell and molecular biology techniques such as RT-qPCR, immunoblotting, histology and tissue culture. This project would suit an individual with a background in biochemistry, physiology, molecular biology or related discipline.
About the DTP
This studentship is offered as part of the White Rose BBSRC Doctoral Training Partnership (DTP) in Mechanistic Biology, which brings together the research of the world-class molecular and cellular bioscience centres at the White Rose universities of Leeds, Sheffield and York.
Our mission is to train excellent bio-scientists who understand how living systems work and can innovate to address global challenges, such as the impact of climate change, a healthier old age, sustainable food production, land use and energy production.
What is on offer?
This is a core studentship for entry in October 2024.
Join us and you will receive a 4-year, funded PhD programme of research and skills training, with cross-disciplinary supervision, plus a structured programme of cohort-wide training and networking events. A highlight is the annual symposium, which is planned and delivered by students.
A unique part of your training will be the Professional Internships for PhD Students (PIPS), where you will spend three months at a host organisation of your choosing, gaining experience of work in a professional environment, and acquiring transferable skills that will be beneficial in your future career.
How to apply – Expression of Interest
Students may apply for up to three projects anywhere in the Doctoral Training Partnership (DTP). Applications will be to the DTP centrally, using an online Expression of Interest (EoI). The EoI will include:
§ CV information; not submitted separately
§ Equality, Diversity and Inclusion (EDI) data
§ Names of two referees
Deadline for EoIs is midnight Sunday 7th January 2024.
Submit EoIs using this link: https://leeds.onlinesurveys.ac.uk/white-rose-bbsrc-dtp-expression-of-interest-form
Shortlisted candidates will be required to make formal applications to the Graduate School at each institution, supplying the necessary paperwork.
Interviews will be held either Friday 2nd and Monday 5th to Friday 9th February, or Monday 19th to Friday 23rd and Monday 26th February 2024, in-person at Leeds, Sheffield and York, with a panel representing all 3 Universities. Shortlisted candidates will be notified of a specific time/date to attend. If you have applied for more than one project and are selected for interview, you will be interviewed only once.
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Bartoli F, Debant M, Chuntharpursat-Bon E, Evans EL, Musialowski KE, Parsonage G, Morley LC, Futers TS, Sukumar P, Bowen TS, Kearney MT, Lichtenstein L, Roberts LD, Beech DJ. Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity. J Clin Invest. 2022 Mar 1;132(5):e141775. doi: 10.1172/JCI141775. PMID: 35025768; PMCID: PMC8884896.
Whitehead A, Krause FN, Moran A, MacCannell ADV, Scragg JL, McNally BD, Boateng E, Murfitt SA, Virtue S, Wright J, Garnham J, Davies GR, Dodgson J, Schneider JE, Murray AJ, Church C, Vidal-Puig A, Witte KK, Griffin JL, Roberts LD. Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis. Nature Commun. 2021 Mar 26;12(1):1905. doi: 10.1038/s41467-021-22272-3. PMID: 33772024; PMCID: PMC7998027.
McNally BD, Moran A, Watt NT, Ashmore T, Whitehead A, Murfitt SA, Kearney MT, Cubbon RM, Murray AJ, Griffin JL, Roberts LD. Inorganic Nitrate Promotes Glucose Uptake and Oxidative Catabolism in White Adipose Tissue Through the XOR-Catalyzed Nitric Oxide Pathway. Diabetes. 2020 May;69(5):893-901. doi: 10.2337/db19-0892. Epub 2020 Feb 21. PMID: 32086288.
1. Knuiman P, Straw S, Gierula J, Koshy A, Roberts LD, Witte KK, Ferguson C, Bowen TS. Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure. ESC Heart Fail. 8: 898-907. 2021.
2. Espino-Gonzalez E, Tickle PG, Benson AP, Kissane RWP, Askew GN, Egginton S, Bowen TS. Abnormal skeletal muscle blood flow, contractile mechanics and fibre morphology in a rat model of obese-HFpEF. J Physiol. 599(3):981-1001. 2021.
3. Caspi T, Straw S, Cheng C, Garnham J, Scragg J, Smith J, Koshy A, Levelt A, Sukumar P, Gierula J, Beech D, Kearney M, Cubbon R, Wheatcroft S, Witte K, Roberts L, Bowen TS. Unique transcriptome signature distinguishes heart failure patients with systemic myopathy. J Am Heart Assoc. 9(18): e017091. 2020
4. Bowen TS, Eisenkolb S, Drobner J, Fischer T, Werner S, Linke A, Mangner N, Schuler G, Adams V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. FASEB J. 31(1):60-71, 2017.
1) N. Endesh, E. Chuntharpursat-Bon, C. Revill, N. Y. Yuldasheva, T. S. Futers, G. Parsonage, N. Humphreys, A. Adamson, L. C. Morley, R. M. Cubbon, K. R. Prasad, R. Foster, L. Lichtenstein*, D. J. Beech. Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress. Liver International (IF 8.754) *corresponding author. Online ahead of print. doi: 10.1111/liv.15646.
2) E. Chuntharpursat-Bon, O.V. Povstyan, M.J. Ludlow, D.J. Carrier, M. Debant, J. Shi, H.J. Gaunt, C.C. Bauer, A. Curd, T.S. Futers, P.D. Baxter, M. Peckham, S.P. Muench, A. Adamson, N. Humphreys, S. Tumova, R.S. Bon, R. Cubbon, L. Lichtenstein, D.J. Beech. PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing. Communications Biology 2023 Apr. doi: 10.1038/s42003-023-04706-4
3) F. Bartoli, M. Debant, E. Chuntharpursat-Bon, E.L. Evans, K.E. Musialowski, G. Parsonage, L.C. Morley, T.S. Futers, P. Sukumar, T.S. Bowen, M.T. Kearney, L. Lichtenstein, L.D. Roberts, D.J. Beech. Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity. J Clin Invest. 2022 1;132(5):e141775. doi: 10.1172/JCI141775.
4) V. Caolo, M. Debant, N. Endesh, T.S. Futers, L. Lichtenstein, F. Bartoli, G. Parsonage, E.A. Jones, D.J. Beech. Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells. eLife. 2020 2;9: e50684.