College/MRC studentship
Mesenchymal stem cells as endogenous regulators of inflammation: Changes in chronic inflammation.

Lead Supervisor: Dr Helen McGettrick

Institute: University of Birmingham, School of Immunity & Infection , College of Medical & Dental Sciences
Project duration: 3 years 
Funded by: College and MRC
Applications are invited for a 3 year PhD studentship to investigate the immunomodulatory actions of mesenchymal stem cells (MSC) and how these change in chronic inflammatory disorders such as Rheumatoid arthritis (RA). The project will be based on unique multi-cellular in vitro models that incorporate primary human MSC and endothelial cells, with the view to applying findings to in vivo pre-clinical models of inflammation as required. The student will be integrated into the multidisciplinary Leukocyte Trafficking Research Group at the University of Birmingham (www.birmingham.ac.uk/leukocyte-trafficking), and collaborate with groups in the Centre for Translational Inflammation Research located within University Hospital Birmingham. 
MSC are multi-potent stromal precursor cells with the potential to differentiate and repair tissue. We believe they also act as endogenous regulators of inflammation, actively moderating the inflammatory infiltrate to allow resolution of the response. One way they can achieve these effects is by talking to neighbouring endothelium in the blood vessel wall. Using novel multi-cellular models, we have recently shown that MSCpotently suppress the response of endothelial cells to inflammatory cytokines, reducing the recruitment of flowing leukocytes. In 3D tissue constructs, we also observed that MSC altered leukocyte migration into tissue matrix and that this was dependent on the differentiation status of the MSC. Thus, we hypothesise that under certain conditions MSC change their phenotype, no longer acting as brakes on leukocyte recruitment, and possibly taking on a stimulatory state. As an example, synovial fluid from patients with RA changed the transcriptional profile of healthy MSC, but whether MSC acquire a pathogenic phenotype during the development of RA has yet to be investigated. Understanding these pathways influencing MSC function has potential for development of therapeutic strategies that mimic the actions of 'healthy' MSC or inhibit their pathogenic transformation, to manipulate inflammatory responses in disease.

Person Specification
Applicants should have a strong background in biological or biomedical sciences. They should have a commitment to stem cell research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject. 
This position is fully funded for university fees and a stipend at standard RCUK rate (for an October 2014 start) 
How to apply
Enquiries or applications including a CV, names and addresses of two referees and a covering letter should be sent to Nicola Windridge, Research and Knowledge Transfer Office, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT or email n.j.windridge@bham.ac.uk 
The closing date is Monday 13th January 2014

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