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MRC DiMeN Doctoral Training Partnership: Project MicroAge : A tissue engineered discovery platform for improving muscle responses to exercise in ageing and spaceflight


MRC DiMeN Doctoral Training Partnership

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Dr JR Henstock , Prof A McArdle No more applications being accepted Competition Funded PhD Project (Students Worldwide)
Liverpool United Kingdom Bioinformatics Biomedical Engineering Biophysics Cell Biology Medical Physics Pharmaceutical Chemistry

About the Project

Astronauts lose muscle mass despite performing considerable exercise in space, since their cellular adaptation to exercise is somehow abnormally impaired by microgravity. On Earth, our muscles also respond less well to exercise as we get older, resulting in reduced muscle mass, loss of strength and frailty.

Our team have demonstrated that reactive oxygen species (ROS) generated during exercise stimulate the activation of specific transcription factors which increase the production of cytoprotective proteins. However, these responses are impaired in muscle from older humans, and analogously may also be attenuated in astronauts in microgravity. This comparison is the basis for our current research at MicroAge, and to do this we have constructed an experimental bioreactor that will soon fly on the International Space Station. The bioreactor uses an ‘organ-on-a-chip’ type technology to support bioengineered micro-muscles created from human cells, with microfluidic plumbing to refresh nutrients and collect secreted biomolecules, and an electrical stimulation circuit to enable the micro-muscles to undergo contractile exercise.

One of our goals is to discover drugs which correct the faulty signalling, since these will help us maintain muscle mass as we age and will enable longer-duration (e.g. interplanetary) spaceflight missions. As part of our team, you will use our existing muscle bioreactor to investigate interventional drugs that can restore the ability of human muscle to respond to exercise during ageing (or in spaceflight). Your initial project goals will be:

 To determine key biomarkers (cytokines, myotube diameter, mitochondrial respiration rate, force generation, etc.) and develop practical methods to measure them.

 To test the effectiveness of novel drugs, nutritionally-derived supplements, and gene/cell therapies to recover and rescue the phenotype of aged muscles.

You will get training in a wide range of interdisciplinary skills (how biology interfaces with mechanical and electrical engineering), learn how we translate basic scientific discoveries into therapeutics, and develop highly valuable quantitative skills. The project links biology across multiple scales: from biochemical signals, through organelles and cells, to visible changes is tissue function. The collaboration with industry and our ongoing acquisition of multidimensional data from ISS microgravity experiments gives you a unique opportunity for developing new technology and underpinning world-leading scientific advances.

The DTP will enable you to work closely with our project partners at the UK Space Agency and Kayser Space Ltd., expanding our existing technology from a specific spaceflight application to a broader range of investigative uses in discovery medicine. Kayser have extensive experience of designing and manufacturing miniaturised bioreactor systems and will help you design, manufacture and test new hardware using commercially appropriate techniques and ISO/QA standards. You will also be encouraged to develop your skills in science commination via the UKSA and our exciting outreach programme involving patient groups, schools and the local community, and take charge of updating our interactive project app to support public awareness of our research.

For more information follow us on Twitter @jhenstock , @Anne91011 and @malcolm_mjj and see links to biographies for the whole team at https://www.liverpool.ac.uk/ageing-and-chronic-disease/microage-in-partnership-with-the-uk-space-agency/

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

Funded by the MRC for 3.5yrs, including a minimum of 3 months working within the industry partner.

Funding will cover UK tuition fees and an enhanced stipend (around £17,785) only. We aim to support the most outstanding applicants from outside the UK. We 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: https://bit.ly/3kPNjoJ

iCASE partner: http://www.kayserspace.co.uk/

Studentships commence: 1st October 2021.
Good luck!

References

1. Jones S, McArdle A, Henstock J, Hoettges K, Janvier A, McArdle C, Jackson L, Zolesi D, Neri G, Jackson MJ. Microage: Microgravity as a model for accelerated skeletal muscle ageing. Proceedings of the International Astronautical Congress, IAC 2019 (Vol. 2019) [https://iafastro.directory/iac/paper/id/49245/abstract-pdf/IAC-19,A1,8,10,x49245.brief.pdf?2019-03-28.10:26:54]

2. Jackson MJ, Stretton C, McArdle A. Hydrogen peroxide as a signal for skeletal muscle adaptations to exercise: What do concentrations tell us about potential mechanisms?. Redox Biology 29:101484 [https://www.sciencedirect.com/science/article/pii/S2213231720301142]

3. Janvier AJ, Canty-Laird EG, Henstock JR (2020) A Universal Multi-Platform 3D Printed Bioreactor Chamber for Tendon Tissue Engineering. Journal of Tissue Engineering 11, 1-15 [https://journals.sagepub.com/doi/pdf/10.1177/2041731420942462]


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