MRC DiMeN Doctoral Training Partnership: Understanding skeletal tissue responses to sex and menopause in osteoarthritis

Osteoarthritis (OA) is a major chronic degenerative joint disease that affects a significant number of the ageing population representing the largest cause of disability and pain in people over 50 years of age. Despite this high prevalence and severity, there are still very limited treatment options available. OA pathology affects all tissues of the musculoskeletal system, including articular cartilage degeneration, osteophyte formation, ligament ossification, subchondral bone sclerosis and loss of muscle mass. It is also clear that women develop more severe disease, especially following the menopause, and that hormone replacement therapy is not a successful avenue to decrease OA development.

Sex dimorphisms are clear in skeletal tissues in general, however the large majority of research is still being performed on male tissues and in vivo models. A consequence of this is the lack of knowledge about how female sex and specific events such as the menopause affect articular function and health, and their impact on OA development.

In this project, our main objective is to describe how sex and menopause contribute to OA development at the individual, tissue and cellular levels.

This project will include a number of varied and complementary skills in a multidisciplinary training environment: the student will learn in vivo skills in mice, in vitro models that recapitulate the mechanical environment of the cells, as well as in silico computer modelling to assess how individual tissue functions affect overall joint OA development.

Output measures will be measured by a range of methods such as state-of-the-art imaging (micro-CT), histological assessment of these tissues using various embedding methods and staining, RNA-sequencing and the use of pathway analysis tools. In parallel, the student will gain experience in measuring mechanical properties of tissues across the scales, as well as exploring the effects of the mechanical environment in vivo and in vitro. Finally, the computer modelling will be used to test mechanical tissue interactions and their potential effects on bone structure and function, and compared directly with in vivo datasets. This wide range of skills that the student will develop across the project will support their development in research and make them very competitive for their future careers, with very complete and varied research skills.

In parallel, the student will be supported in developing non-lab based skills such research communication (e.g., national and international conferences, with their own peers in the University, and with the public), time and project management, and grant writing. In addition, their career development will be supported across a wide range of training opportunities within the University and when needed via external providers. These may include mentorship for grant/fellowship applications, networking, career development options and networking.

Dr Poulet’s Webpage: https://www.liverpool.ac.uk/people/blandine-poulet

Dr Readioff’s Webpage: https://www.liverpool.ac.uk/people/rosti-readioff

Prof Comerford’s Webpage: https://www.liverpool.ac.uk/people/eithne-comerford

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, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/