Recombinant protein therapeutics for pain in osteoarthritis: from bench to preclinical models
Supervisors: Dr Lisa Mullen Prof Andrew Dilley
Application deadline: Friday 24 April 2026
Funded PhD Project (UK Students Only)
About the Project
Applications are invited for a 3-year funded PhD studentship at Brighton and Sussex Medical School.
Project details
Osteoarthritis (OA) is the most common joint disease worldwide, affecting c. 10 million people in the UK alone. The hallmarks of OA are degradation of joint cartilage and changes to the underlying bone. These structural changes are progressive and eventually result in a non-functional joint for which the only treatment is major joint replacement surgery. A major hallmark of OA is intense pain in the affected joint(s) that can severely compromise mobility and quality of life. Despite many developments in our understanding of the pathogenesis of OA, there are no effective disease-modifying or pain-relieving treatments for OA. The neurotrophin, nerve growth factor (NGF) protein is the best validated target in OA pain, with proven analgesic effects in preclinical and clinical studies. However, development of NGF-targeted therapies have been hampered by unwanted side-effects.
A novel protein drug-delivery system (known as the latency-associated peptide (LAP) technology) enables creation of protein therapies in a biologically inactive form, that are then activated in the body only at the site(s) of disease. This localised approach eliminates the side effects seen with more standard therapies. The aim of this project is to use this drug-delivery strategy to engineer antibody fragments specific for NGF receptors to inhibit NGF signalling within the OA joint and prevent activation of the local nerve fibres that generate pain.
The aims of the project are to: engineer, clone and express recombinant LAP-fusion proteins that can inhibit NGF receptors, assess the therapeutic potential of these LAP proteins on relevant cell types in vitro and in vivo, and define the relationship between cartilage degradation and pain. Key methodologies include cloning and expression of recombinant proteins, RNA sequencing, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Enzyme-Linked Immunosorbent Assays (ELISAs) and Western blotting as well as in vivo models of disease.
Research Environment
The successful candidate will integrate into a well-established, multidisciplinary biochemistry/immunology/rheumatology group at BSMS consisting of teams led by Dr Lisa Mullen, Professor Sandra Sacre, and Professor Katherine Staines at the University of Brighton. These groups are also part of a wider vibrant and active Musculoskeletal Group which consists of teams from the University of Sussex, University of Brighton and BSMS creating a dynamic and collaborative environment conducive to productive training.
Dr Lisa Mullen’s expertise is in generating novel recombinant proteins for efficient delivery to sites of disease in vivo as well as interests in innate immune responses in rheumatic disease. Professor Andrew Dilley is professor of Neuroanatomy whose research encompasses both laboratory and human studies into the role of peripheral neuroinflammation in chronic musculoskeletal pain.
The project provides diverse training opportunities, enabling the student to gain crucial skills across various areas such as cell biology, cell signalling, drug targeting, recombinant protein therapeutics and disease models. On completion of the project, it is expected that future post-doctoral research in the fields of cell or molecular biology, protein biochemistry and/or therapeutics will be the natural progression from this work.
Entry requirements
This studentship is suitable for those with background in biochemistry, molecular biology, biomedical science or another relevant subject area. We invite applications from students who have received or are on target to achieve a relevant undergraduate degree with minimum 2:1 classification (or equivalent). An MSc and previous laboratory experience are desirable but not essential.
How to apply
Applicants must apply through the University of Brighton application portal (StudentView) where they can submit a CV and complete the application form. The deadline for applications is 24 April 2026. Interviews will be held in May 2026. Informal enquiries are welcome and should be submitted to Dr Lisa Mullen (l.mullen@bsms.ac.uk).
Funding Notes
This is a 3-year PhD studentship funded by Brighton and Sussex Medical funded, starting on 1 October 2026. Funding will cover tuition fees for UK students (at the Home rate), a stipend at the UKRI rate and a research allowance which will cover research running costs. International applicants are welcome to apply but will be required to cover the difference between Home and International fees.
References
- Simoes FA, Scutt G, Mengozzi M, Mitchell SA, Keen J, Staines KA, Troeberg L, Poulet B, Pitsillides AA, Mullen LM. Development of a translational strategy for using TIMP-3 to inhibit aggrecanase activity in osteoarthritis. Osteoarthritis Cartilage. 2025 Sep 8:S1063-4584(25)01131-8. doi: 10.1016/j.joca.2025.09.002. Epub ahead of print. PMID: 40930457.
- Alberts BM, Sacre SM, Bush PG, Mullen LM. Engineering of TIMP-3 as a LAP-fusion protein for targeting to sites of inflammation. J Cell Mol Med. 2019 Feb;23(2):1617-1621. doi: 10.1111/jcmm.14019. Epub 2018 Nov 18. PMID: 30450736; PMCID: PMC6349231
- Mullen L, Adams G, Foster J, Vessillier S, Köster M, Hauser H, Layward L, Gould D, Chernajovsky Y. A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints. Ann Rheum Dis. 2014 Sep;73(9):1728-36. doi: 10.1136/annrheumdis-2013-203513. Epub 2013 Jun 27. PMID: 23813971.
- Mullen L, Adams G, Layward L, Vessillier S, Annenkov A, Mittal G, Rigby A, Sclanders M, Baker D, Gould D, Chernajovsky Y. Latent cytokines for targeted therapy of inflammatory disorders. Expert Opin Drug Deliv. 2014 Jan;11(1):101-10. doi: 10.1517/17425247.2014.863872. Epub 2013 Dec 3. PMID: 24294995.