MRC DiMeN Doctoral Training Partnership: Tissue regeneration using nano-biologics

This PhD project combines cutting edge science with innovative therapeutic development, under the supervision of two experts in the field, Professor Paul Genever (York) and Dr Owen Davies (Loughborough). The promise of mesenchymal stem cell (MSC) therapies to offer a solution to regenerate tissue lost to damage or disease has been limited by a lack of understanding of their mechanism of action (i.e. how they achieve their therapeutic effect) and an inability to reproducibly manufacture enough MSCs to meet clinical demand. Recent evidence has suggested that stem cells, at least in part, achieve their therapeutic effects through the secretion of bioactive nanoparticles called exosomes. 

In many ways, exosomes can be viewed as the body’s postal service, enabling the safe transport of biological factors essential for tissue development, homeostasis and repair. Exosomes have potential therapeutic advantages over cells in that they are comparatively safe, stable and potentially more cost-effective. As such, exosomes are increasingly viewed as an exciting new biotherapeutic paradigm. However, several key challenges currently prevent promising exosome therapies from reaching a global market and benefitting patients. Importantly, we need to address exosome identity, consistency, mechanism of action and strategies for their isolation. 

This PhD is designed to tackle these challenges by identifying the most potent tissue-forming exosomes derived from immortalised clonal MSC lines, underpinned by mechanistic biology. The focus will be on bone regeneration to address tissue loss caused by trauma, tumour resections and major global diseases such as osteoporosis.

To achieve this, you will isolate exosome subtypes from different immortalised MSC clonal lines, which we have already generated and characterised in the lab. You will test the exosome subtypes using in vitro and ex-vivo bone-forming assays, including rapid osteogenic reporter screens. You will characterise the pro-osteogenic exosome subtypes by nanoparticle tracking analysis, western blotting and multi-omic analyses and test candidate mechanisms of action by pathway targeting and genetic modification. Collectively, your research will accelerate the preclinical development of a novel biotherapeutic for an important and unmet clinical need.

You will be based in the Department of Biology at the University set in the beautiful, historic city of York. You will join a vibrant community of like-minded biomedical research scientists and fellow PhD students. You will have access to state-of-the-art equipment through our renowned Technology Facility and the opportunity to develop your scientific and transferable skills through a comprehensive training programme. Unique to this project, you will also benefit from the expertise and facilities for exosome characterisation and analysis available at Loughborough University. We have excellent industrial collaborators including our own spin-out company, Mesenbio, which will provide exposure to commercial development and a genuine route for the clinical translation of your research.

Paul Genever: 

https://www.york.ac.uk/biology/research/developmental-biology/paul-genever/

https://www.geneverlab.info/ 

https://www.mesenbio.net/ 

https://www.visityork.org/ 

Owen Davies:

https://www.lboro.ac.uk/schools/sport-exercise-health-sciences/people/owen-davies/ 

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, York 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: https://www.dimen.org.uk/blog 

Further information on the programme and how to apply can be found on our website: https://www.dimen.org.uk/how-to-apply