Cellular senescence is the permanent loss of a cell’s ability to divide, and is associated with several age-related pathologies including neurodegenerative disease, impaired wound healing, and cancer. Several recent studies have demonstrated the ability of drugs that selectively target senescent cells (called senotherapeutics) to reduce age-related disease severity and increase healthy lifespan in laboratory animals. Thus, there is considerable and growing interest in the utility of senotherapeutics to increase healthy lifespans in humans.
One major difficulty impeding clinical development of senotherapeutics is a lack of biomarkers of senescence to monitor drug responses. Recent evidence suggests that the levels of specific glycans (sugars) are altered on the surface of senescent cells, possibly identifying a novel source of senescence-specific biomarkers.
Recently, our group and others have shown that senescent cells release membrane-bound vesicles termed extracellular vesicles (EV). The cargo of EV reflects the parent cell, including the glycome (the landscape of sugars on their surface). They are found in all body fluids, are readily detectable and stable, making them an ideal source of biomarkers. In addition, EV play a number of functional roles in health and disease by acting as messengers between cells.
The aim of this project is to test the hypothesis that the EV glycome plays a role in the function of senescent cells and represents an ideal biomarker for monitoring senescence, and by extension biological age and related disease.
The project will use a wide variety of state-of-the-art molecular and cell biology techniques, alongside computational (‘big data’) analyses - highly sought after skill-sets in academia and the commercial sector. The project supervisors have a strong track record of supporting PhD students’ career progression and publishing work arising from their projects, and the School hosts a thriving and diverse PhD student community.
This project is a collaboration with Ludger Limited, a world leader in glyco-analytical technology with a business interest in glycan-based health monitoring and biomarker development. It will include a placement with Ludger and the opportunity to gain experience of working in a commercial biotech environment. The research will increase understanding of the nature and function of the EV glycome and potentially identify novel biomarkers of ageing to facilitate the translation of a new wave of therapies targeting age-related multimorbidity.
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: 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:
http://www.dimen.org.uk/how-to-apply/application-overview
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