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About the project

Osteoarthritis (OA) is a highly painful disorder and current drugs provide only minimal relief and are associated with adverse side-effects. In patients with OA of the knee, inflammation of the synovial joint lining (synovitis) is associated with pain severity. The inflammatory milieu of knee OA patient synovial fluid causes sensitization and hyper-excitability of nociceptors and we have shown that the phenotype of the OA synovial fibroblast is a major contributor to the pro-inflammatory synovial fluid environment in OA patients. Furthermore, we have found that fibroblasts at sites of patient-reported pain exhibit distinct phenotypes that promote neuronal growth. Therefore, we hypothesise that therapeutics that disrupt synovial fibroblast neuronal cross talk will alleviate pain in patients with knee OA. The aims of the project are first to characterise the transcriptome and secretome of these pain-associated fibroblasts in order to identify candidate targets that mediate neuronal cell growth and activity. Secondly, working with the Nucleic Acid Therapy Accelerator, to then design and test the efficacy of novel antisense therapeutics at impairing fibroblast neuronal cross talk in bespoke experimental models of pain. These cellular models will utilise murine dorsal root ganglia cultured in microfluidic chambers, enabling the assessment of nociceptor functional activity and growth.

Eligibility
Academic requirement
Minimum qualifications and experience to undertake a research degree are detailed in the QAA UK Quality for Higher Education. For some subject areas, there is also an expectation that an individual will have undertaken a Masters qualification before beginning a doctoral programme. Candidates should possess the relevant qualifications and/or experience to demonstrate a capability to undertake a doctorate, which will be assessed during the recruitment process.  More details can be found on the MRC website

Residency requirements
These studentships are available to UK nationals, EU nationals and international applicants.  Full details on eligibility, including residence requirements can be found on the Full Eligibility Criteria or on the UKRI website

Tuition fees
Applicants that are classed as an international student will receive a full award, to include a stipend and tuition fees at the home level.  International applicants will need to submit evidence with their application that they are able to “top up” the home tuition fee rate to the relevant institution international fee rate for 3.5 years from a scholarship or other source, not to be from your personal/family funds.  This could be between £21,000 and £25,000 (subject to increase for 2021 academic year).

See this project on the IMPACT website

https://more.bham.ac.uk/mrc-impact/phd-opportunities/