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  Neutrophils as initiators and drivers of psoriasis


   Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM)

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  Dr K Shams, Dr Clive McKimmie, Dr F Ponchel  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Psoriasis is a common inflammatory disease that affects 2% of the global population and has a profound impact on the life of those with the condition. Typically, psoriasis is characterised by well-demarcated, red scaly skin plaques that are surrounded by otherwise healthy-looking skin. Despite significant advances in psoriasis research, we do not yet understand why psoriatic plaques and inflammation develop or why adjacent skin is left apparently unaffected. Understanding how and why plaques develop at specific sites, will aid the development of new therapeutic approaches for psoriasis and potentially other inflammatory skin disorders.

A range of skin cells drive inflammation in psoriasis, with important roles for T-cells, dendritic cells, and keratinocytes. In addition, neutrophils are present in large numbers in psoriasis, which form clusters in the outermost layers of the skin. However, the role of neutrophils in psoriasis remains largely unexplored. In recent years, there is new emerging evidence that they may be key players in psoriasis pathogenesis.

This project will investigate the triggers that lead to the recruitment and clustering of neutrophils to specific skin sites in psoriasis. Using a range of state-of-the art techniques, we will explore how neutrophils interact with the other cutaneous cells including keratinocytes, T-cells and dendritic cells. It is expected that the project will provide novel insights into cell-cell interactions that drive skin inflammation and may lead to novel therapeutic targets being identified.

The successful candidate will work alongside a team of clinicians and basic scientists, with work being conducted on a range of human skin samples. The project will involve comprehensive training in and use of a range of techniques, including;
• quantitative-PCR
• ELISA
• flow cytometry
• immunohistochemistry
• tissue culture of primary human cells
• in vitro migration assays
• in vitro and in vivo models of psoriasis/skin inflammation

The University of Leeds is a thriving and dynamic setting for world-class skin research, with a supportive environment and extensive range of expertise. It was awarded the Sunday Times University of the Year in 2016, based on the experience of students. The Department of Dermatology is a tertiary referral centre, with extensive experience of clinical trials, collaborations with pharmaceutical companies, translational- and basic research and large numbers of patients with inflammatory skin disorders. The successful candidate will be based in the supportive and well-resourced environment of the Leeds Institute of Rheumatology and Musculoskeletal Medicine (LIRMM), which is a world-leading centre for translational inflammation research.

The successful applicant should hold, or be expected to obtain, at least an upper second-class degree in biological sciences (or equivalent). A Masters degree in a relevant subject and previous relevant research experience would be a significant advantage.



Funding Notes

Interested candidates should contact the lead supervisor (Dr Kave Shams, [Email Address Removed]) with their CV attached, to discuss their application

References

• Schön et al. Sexy again: The renaissance of neutrophils in psoriasis. Experimental Dermatology 2016
• Shams et al. Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2. Journal of Investigative Dermatology 2016
• Healy et al. Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise. British Journal of Dermatology 2015

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