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Regulatory T cell-derived extracellular vesicles in patients with rheumatoid arthritis:


   School of Medicine

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  Dr Oksana Kehoe  Applications accepted all year round  Funded PhD Project (UK Students Only)

About the Project

One in every 16 of people in the UK live with an autoimmune condition causing them pain, difficulty, lost opportunities in work and in life, and in many cases placing them at risk of early death. Autoimmunity occurs when the immune system attacks the body. Regulatory cells (also called Tregs) are cells of immune system which have a role in regulating or suppressing other cells in the immune system. Tregs control the immune response to self and foreign particles and help prevent autoimmune disease. Understanding how Tregs supress cells in the immune system could help improve treatments for people with autoimmune conditions including lupus, type 1 diabetes, Sjögren syndrome, multiple sclerosis and rheumatoid arthritis. In rheumatoid arthritis, the immune system destroys the lining of the joints. At present, autoimmune conditions cannot be cured. Tregs communicate with other cells in the immune system by producing the little particles called extracellular vesicles. This project will explore these particles to find out what’s inside them and how they differ in healthy people and patients with rheumatoid arthritis using a variety of different tests. Next, this project will explore how the extracellular vesicles function. We will add the particles into a dish with immune cells from patients with rheumatoid arthritis. These cells are overactive, which causes the pain, inflammation and swelling in the joints, so we want to see if our extracellular vesicles can suppress these immune cells. If these experiments are successful and the extracellular vesicles contain anti-inflammatory properties, then they have the potential to be applied to many different autoimmune conditions. CD4+CD25+ / highCD127low/− regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance, by preventing autoimmunity and chronic inflammation. In this project we would like to explore whether the biological characteristics and functionality of regulatory T cell-derived extracellular vesicles in patients with rheumatoid arthritis differed from those in healthy donors. In this study we aim to investigate immunoregulatory functional properties of Tregs-derived EVs in rheumatoid arthritis patients and healthy volunteers. The project will meet this aim through the achievement of three primary objectives:  Isolate EVs and characterise molecular cargo of Tregs-derived EVs in rheumatoid arthritis patients and healthy volunteers;  Determine the suppressive efficacy of Tregs-derived EVs in vitro;  Identify the vesicular factors that are responsible for their suppressive effects; This project provides the opportunity to work closely with researchers at different Universities, clinicians and human patient samples/data to address a pertinent clinical question that will likely lead to patient benefit. The studentship will be based at the RJAH Orthopaedic Hospital in Oswestry, however, there will be the occasional need to attend training at Cardiff University and the University of East London and at Keele University.

For any further information or for an informal chat about the project please contact: Dr Oksana Kehoe on [Email Address Removed]

Oswestry Keele Orthopaedic Research Group


Funding Notes

Funding is available to cover 100% UK student tuition fees and consumables for 3 years full time.
Funding will cover all research and travel costs.
No stipend is available for this project.
Non-UK applicants will be considered if they are able to self-fund any additional tuition fee costs that may exist and can obtain a visa to study in the UK.

References

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