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Phd Studentship - Regulation of leukocyte recruitment by fibroblast-endothelial interactions: Under

Employer
Global Academy Jobs
Location
United Kingdom
Closing date
Mar 14, 2018

Job Details

Details

Research interests/description of main research theme:
Applications are invited for a prestigious and distinctive four year full time MRC CASE PhD Studentship starting in Autumn 2017. The PhD studentship is a collaborative project between the Institute of Inflammation and Ageing (IIA; http://www.birmingham.ac.uk/research/activity/inflammation-ageing/index.aspx) at the University of Birmingham, UK and the ATI Translational Research Unit at Novartis, Basel, Switzerland (https://www.nibr.com/our-research/disease-areas/autoimmunity-transplantation-inflammatory-disease), where the student will spend ~6 months training during the studentship.

Rheumatoid arthritis (RA) is a major cause of disability affecting ~1% of the UK population. Biological treatments that target leukocytes or their cytokine produces have improved outcomes, but they do not reverse tissue damage nor do they cure disease. During the earliest stages of disease, conventional treatments are significantly more effective, but the reasons for this are not clear. Based on high impact recent discoveries,this project takes a radical approach to understanding the role played by stromal (endothelial and fibroblast) populations in the early phases of disease.

Synovial fibroblasts of the RA joint are major contributors to joint damage and disease persistence, but have yet to be targeted therapeutically. These cells actively regulate leukocyte recruitment through interactions with endothelial cells (EC) that line blood vessels (McGettrick et al., 2009). We have characterised a unique phenotype of synovial fibroblasts seen in early arthritis that distinguishes acute resolving arthritis (Res) from the early stages of RA (eRA). Res fibroblasts induce an immunosuppressive response in EC that limits the magnitude of leukocyte recruitment to the joint. However this capacity is lost in eRA synovial fibroblasts (Filer et al 2017). This change represents a phenotypic swtich from protective to pathological synovial fibroblast-endothelial cell interactions.

The aim of this PhD studentship is to interrogate the molecular mechanism underpinning the cellular cross-talk between the synovial fibroblasts and EC. To achieve this the student will have access to a unique resource of cellular material from the Birmingham Early Arthritis Cohort (BEACON). They will use our unique flow based adhesion assays to provide resources which will be analysed using high throughput analysis platforms (RNAseq, proteomics, phosphokinase arrays, metabolomics) at Novartis, complemented by live whole tissue imaging platforms and chimeric mouse models of arthritis incorporating human synovial tissue and cells in Birmingham.

The work will generate new insights into disease pathogenesis and provide novel targets for drug development. Ultimately, we aim to test whether mimicking the actions of Res SF or inhibiting those of ‘pathogenic’ eRA or RA SF can reset the balance of leukocyte recruitment, thus halting disease progression.

Person Specification
Applicants should have a strong background in cell biology and/or immunology. They should have a commitment to research in inflammation biology and rheumatology research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree, or equivalent, in a relevant biological subject.

How to apply


Informal enquiries should be directed to Dr Helen McGettrick (h.m.mcgettrick@bham.ac.uk)
Applications should be directed to Dr Helen McGettrick (email h.m.mcgettrick@bham.ac.uk).

To apply, please send:


• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
 

Funding Notes


Funded PhD (4 years): open to UK and EU Graduates.

EU applicants are advised to check the level of funding they are eligible for using MRC guidelines: http://www.ukcisa.org.uk/Information--Advice/Fees-and-Money/Government-Student-Support#layer-6229

Applicants from EU countries other than the UK are generally eligible for a fees-only award. To be eligible for a fees-only award, an applicant must be ordinarily resident in a member state of the EU.

The student stipend will be funded at MRC CASE Studentship rates.

Start date: October 2018 or ASAP
 

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