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Characterisation of a pre-osteoblast subset of human mesenchymal stem cells: implications for novel osteoarthritis and osteoporosis treatment developm

PGR-P-66

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Non-funded
Additional supervisors
Elena Jones
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

Osteoarthritis (OA) and osteoporosis (OP) are the most common age-related skeletal diseases. They seriously affect patient&rsquo;s quality of life and represent a significant healthcare burden to the UK society. In OP, bone tissue becomes weaker and fractures occur more often as a result of an imbalance between new bone formation and old bone resorption. In OA, sporadic bone resorption episodes occur due to biomechanical stress in response joint loading. New bone formation can become excessive and lead to the destruction of the articular cartilage lining the joint surface. Current treatments for OP target bone resorption, but not the bone formation pathway, whereas for OA there is no disease-modifying therapies and joint replacement remains the ultimate option to alleviate pain. Our group has a long-standing interest in mesenchymal stem cells (MSCs), which are the earliest progenitors in the bone formation pathway. We have described their native phenotype (CD45-CD271+) and gene expression signature in human bone marrow confirming their undifferentiated and multipotential nature [1,2]. Our recent data has shown that a distinct subset of these cells (CD56+) displays a gene expression signature consistent with pre-osteoblasts (i.e. progenitor cells pre-committed towards bone formation). We therefore hypothesise that this specific subset is numerically and/or functionally impaired in OP and conversely, expanded in OA. In this project we plan to isolate and characterise the CD271+CD56+ subset of MSCs in OP, OA and control age-matched healthy bone using well-established methodologies of clinical samples processing by tissue digestion, functional assays of stem cell differentiation, immunohistochemistry, multiparameter flow cytometry and confocal microscopy imaging. This will be linked to microCT evaluation of the same tissues for structural correlations. RNA sequencing analysis will be performed to investigate pathway differences between bone forming in OA and bone loss in OP. Sorted cell populations will be treated with candidate bone anabolic or inhibitor molecules for their suitability as novel pathway modifiers.

<h2 class="heading">How to apply</h2>

<p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to&nbsp;<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>&nbsp;to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &acirc;&euro;&cent; British Council IELTS - score of 6.5 overall, with no element less than 6.0 &acirc;&euro;&cent; TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221.</p>