PhD Studentship: Targeting osteoblast-endothelial cell interactions in osteoporosis
Research Interests/Main Research Theme:
The MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research (CMAR) is a collaborative venture focussed on understanding how ageing results in loss of musculoskeletal function and using this knowledge to intervene in age-related musculoskeletal decline and disease. One of the Centre’s core aims is to train the next generation of researchers, building capacity in this vital area to ensure that older adults are able to enjoy rather than endure old age.
Osteoporosis is characterised by progressive, age-related trabecular bone loss, resulting in fracture, frailty and disability.
Dr Naylor et al recently showed that inhibition of an osteoblast protein (CD248) could be an ideal therapeutic strategy to reverse inflammation-induced osteoporosis.1 Further work has identified a novel signalling pathway that includes CD248 and has defined specific targets whose deletion leads to protection against age-related bone loss. Furthermore, unpublished findings link this pathway to the newly-characterised “H vessel” endothelial cells. H vessels are a specialised blood vessel type, discovered by Dr Kusumbe et al, that support and control osteoblast trafficking to sites of bone formation.2
This project, therefore, brings together two complementary strands of research and has the potential to advance our understanding of the mechanism by which osteoblasts and H vessel endothelial cells communicate with each other to control bone formation rates.
The CD248 signalling pathway represents a novel therapeutic target for age-related bone loss.
We have developed tools to manipulate and interrogate the CD248 signalling pathway, including genetically modified mice, antibodies blocking critical components of the signalling pathway and recombinant protein fragments mimicking pathway components. These reagents will be used in vivo and in vitro to trigger osteoblast signalling, migration, activity and bone formation.
Techniques including (but not limited to): Microarray/RNASeq, Western blotting, co-culture, real-time cell imaging, state-of-the-art fluorescence whole-mount imaging, in vivo and ex vivo micro-CT and synchrotron sub-micron tomography.
Dr Amy Naylor has identified a novel protein interaction complex linking osteoblast activity with the vasculature. She has all the tools/reagents required to interrogate this interaction and investigate its potential as a therapeutic target. She has experience supervising successful PhD students and was recently awarded a prestigious Career Development Fellowship from Arthritis Research UK to progress her research.
Dr Anjali Kusumbe discovered H vessels and their critical role controlling bone formation. She is a world leader on imaging bone vasculature and has published multiple Nature papers on this subject. A secondment to her lab at the University of Oxford will allow the student to benefit from this expertise.
Dr Simon Jones is a Senior Lecturer at the MRC-ARUK Centre for Musculoskeletal Ageing Research. His research interests include the inflammatory mechanisms that drive osteoarthritis pathology and he has extensive PhD supervision experience.
The student will be part of a wider cohort of 11 CMAR studentships in 2018 and a further 11 in 2019, ensuring peer support and increased networking and collaboration opportunities, both within Birmingham/Oxford and with other affiliated Centres of Excellence. In addition, the student will be integrated into the University of Birmingham Graduate School, undertaking training courses and the PhD seminar series. Training in all aspects of animal handling, molecular biology, cell culture, histology and microCT will be provided. During the secondment period, Dr Kusumbe’s team will provide specialist training in bone sectioning and imaging techniques.
Regular meetings between the sites will give the student insights into the workings of different academic environments and will support their scientific development. The expectation is that, upon completion of the PhD, the student will have acquired a highly competitive skill set on which to base their future career.
Applicants should have a strong background in Biomedical Sciences and ideally also Cell/Molecular Biology and have a commitment to research in Ageing/Rheumatology. They must hold or realistically expect to obtain a First or Upper Second Class Honours Degree in a relevant subject.
How to apply
Informal enquiries and applications should be directed to Dr Amy Naylor (email: firstname.lastname@example.org).
3-year funded studentship through the MRC-ARUK Centre for Musculoskeletal Ageing Research (CMAR). Students should have home or EU status: and have been 'ordinarily resident' in the UK for 3 years prior to the start of the studentship to be eligible for the full award (tuition fees, research support costs, and a tax-free stipend at the Research Council rate). Applicants who have been 'ordinarily resident' in another EU member state may be eligible for a fees only award. Please see RCUK terms and conditions for further information.
This studentship is full-time and will begin on 1st of October 2018
- Naylor A.J, Azzam E, Smith S, Croft A, Poyser C, Duffield J.S, Huso D.L, Gay S, Ospelt C, Cooper M.S, Isacke C, Goodyear S, Rogers M.J, Buckley C.D. (2012) The mesenchymal stem cell marker CD248 (Endosialin) is a negative regulator of bone formation in mice. Arthritis and Rheumatism 64:3334-43
- Kusumbe A.P, Ramasamy S.K, Adams R.H. (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature, 507: 323-8