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MRC DiMeN Doctoral Training Partnership: Elucidating new redox-signalling mechanisms that act to maintain healthy tissues during ageing


MRC DiMeN Doctoral Training Partnership

About the Project

Project Summary
This iCASE MRC studentship provides an exciting opportunity to use a diverse range of cutting-edge techniques, and exploit the advantages of different model systems, to identify new molecular mechanisms, that protect against ageing/age-associated diseases.

Research Project
Reactive oxygen species (ROS) cause cell damage that is a major contributor to many diseases, including cancer, neurodegenerative and cardiovascular diseases, which are increasingly prevalent in our ageing population. However, over the last 10 years, our view of how to limit this damage has been revolutionised. This follows the discovery that low levels of ROS have important, positive, signalling functions, that include initiating protective responses that maintain cell viability/organismal health. For instance, increasing the lifespan of the nematode worm Caenorhabditis elegans and mediating the protective effects of exercise against age-associated loss of muscle (sarcopenia) https://www.nature.com/articles/nrm3801 https://www.sciencedirect.com/science/article/pii/S0098299716300164?via%3Dihub#f0010. Despite, the increasing evidence that localised ROS increases can be beneficial, the mechanisms by which these ROS signals are transduced to protect against ageing/age-associated loss of tissue function remain poorly understood. You will be part of a team combining a range of genetic, biochemical and cell biological approaches to provide answers to this fundamental question.

Dr Veal’s lab have successfully used a combination of high throughput genetic screening and proteomic approaches in model yeast and worms to identify several novel ROS-regulated proteins (Crook-McMahon et al 2014 and unpublished). The goal of your project will be to use standard and cutting-edge molecular and cell biological techniques (including genome editing, RNAi, immunoblotting and confocal microscopy) to investigate whether these proteins mediate the positive effects of ROS in cell (Schizosaccharomyces pombe), tissue (isolated skeletal muscle fibres) and animal (Caenorhabditis elegans) models. By identifying proteins mediating physiological effects of ROS, this project will provide an essential step towards the goal of therapeutically enhancing ROS-induced protective responses to counteract the effects of ageing. The industrial placement, supervised by Dr Conlon, will allow you to use network pharmacology to identify the next step towards translating these discoveries.

Research environment
Dr Veal, and Professor Jackson, lead active and well-established research groups whose primary focus is understanding physiological responses to ROS. Dr Veal’s group https://www.ncl.ac.uk/camb/staff/profile/elizabethveal.html#research is based in the Institute for Cell and Molecular Biosciences (ICAMB) and Institute for Ageing at Newcastle University. ICAMB is a vibrant, well-equipped and highly successful research institute (ranked 2nd nationally for research outputs in REF2014) with PhD students contributing to the majority of our papers. Professor Jackson is the director of the MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing https://www.cimauk.org/profiles and leads a highly successful group of researchers in the Institute of Ageing and Chronic Disease at Liverpool University https://www.liverpool.ac.uk/ageing-and-chronic-disease/research-groups/muscle/. Dr Conlon the CEO of the industrial partner, Nuchido (based in Newcastle) and an expert in network pharmacology, will supervise the industrial placement, which will provide a fantastic opportunity to experience first-hand the process involved in starting to translate findings from ageing research.

Potential applicants are strongly encouraged to contact the lead supervisor for further details before making an application.

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


iCASE Award: Industrial partnership project

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: View Website

Studentships commence: 1st October 2020.
Good luck!

References

[1] Goh GYS*, Winter JJ*, Bhanshali F, Doering KRS, Lai R, Lee K, Veal EA#, Taubert S#. NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting. Aging Cell. (2018) Jun;17:e12743. *equal contribution #corresponding author

[2] Miranda-Vizuete A#, Veal EA#. Caenorhabditis elegans as a model for understanding ROS function in physiology and disease. Redox Biol. (2017) 11:708-714. #corresponding author

[3] Brown JD*, Day AM *, Taylor SR, Tomalin LE, Morgan BA#, Veal EA# (2013) The thioredoxin peroxidase activity of a Prx promotes H2O2-signaling and oxidative stress resistance by oxidizing a thioredoxin family protein Cell Reports 5: 1425-35. (IF=8.0) *equal contribution #co-corresponding author

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