Novel nanoplasmonic sensors for non-invasive detection of senescence

This 3.5 year studentship is part of the Healthy Lifespan Institute (HELSI) at The University of Sheffield. HELSI is dedicated to the understanding and prevention of multimorbidity (the presence of two or more chronic health conditions that create disability and reduce quality of life). We are taking a unique multidisciplinary approach to help people live longer, healthier and more independent lives.

Students within the Healthy Lifespan Institute are valued and active members of the Institute and vital in contributing to our aims and helping to effect real change. You will be part of a wider multidisciplinary network of PhD students (see here) and will have the chance to influence and lead Institute activity, seminars and events, and meeting leaders in the field.


Research Project:
Background
A recent World Health Organisation (WHO) report on healthy ageing begins: 'The world is facing a situation without precedent: We soon will have more older people than children and more people at extreme old age than ever before.' This illustrates starkly the importance of research into healthy ageing. One area of research gaining particular attention is the potential of eliminating 'zombie' cells (termed senescent cells) which accumulate with age and contribute to chronic inflammation and many diseases of ageing, using 'senotherapeutic' drugs which specifically kill senescent cells or alter their secretions.

Several studies in animals using senotherapeutics have shown startling results, with increased lifespan and reduction in age-associated disease. The translation of this into humans, however, is severely impeded by the lack of non-invasive, specific, biomarkers of senescent cell load. The identification of a reliable pharmacodynamic biomarker is important, as it can be used for early assessment of a treatment effect on a potential clinical end point, including patient safety.

Extracellular vesicles (EV) are small, membrane-bound structures released by cells into the surrounding environment, and are abundant in all body fluids. They contain a variety of nucleic acids, lipids and proteins, which provide a signature of the cell from which they were derived. Given the increasing understanding of the altered molecular landscape of senescent cells compared to proliferating counterparts, this raises the tantalising prospect that EVs present in body fluids may hold promise as biomarkers of senescence and that this may be exploited to develop non-invasive, low-cost assays of senescent cell load.

Project aim: We propose a simple, sensitive assay based on the nanoplasmonic analysis of senescent cell-derived extracellular vesicles that could determine senescent cell load and transform the clinical translation of senotherapeutics.

In this project we propose two new approaches to the detection of biomarkers of senescence based on nanoplasmonic detection of biomarkers in senescent cell-derived EV that promise to meet this need.

The project will provide training in a number of advanced techniques spanning biology, chemistry and engineering, all in a translational healthcare context. You will develop skills in cell biology techniques, extracellular vesicle isolation and characterisation, mass-spectrometry and bioinformatic analyses and nanoplasmonic detection technologies, along with opportunities for engagement with patients, the public and our industrial partner, who will act as an external mentor for the project. You will work in partnership with a PhD student based in the Department of Chemistry, who will work with you to develop plasmonic platforms for use in detection of biomarkers as part of a £7.3M EPSRC-funded programme. You will join a multidisciplinary team spanning three faculties at the University of Sheffield with a long and successful track record of PhD supervision and career development.