Exploring the effects of innate lymphocyte derived cytokines including IL-17A, IL-17F and IL-22 on spinal bone derived mesenchymal stem cells (MSC)

Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine and over time leads to excessive bone formation, complete fusion of the vertebrae and the loss of mobility of the spine. The area of connective tissue anchoring tendons or ligaments to the bone is known as the enthesis, in AS this is the primary site of inflammation which then spreads to surrounding tissue. Although new therapies that target key cytokines thought to be involved in the early stages of inflammation, interleukin 17A (IL-17A) and IL-22, are starting to become available, the cellular mechanisms involved remain poorly understood.

We have recently shown that the normal human enthesis has a resident population of lymphocytes that produce IL-22 [1]. We also showed that IL-22 is capable of driving bone-lineage differentiation from mesenchymal stem cells (MSCs) [2]. This PhD project will explore the interaction between cytokines produced by lymphocytes, including IL-17A, IL-17F and IL-22, and MSCs from the spine, to understand how the innate immune system contributes to aberrant new bone formation in AS.

The objectives are:

1- To isolate T-cells as well as MSCs from human spinal tissue by fluorescence activated cell sorting (FACS).

2- To perform transcriptional analysis via RNAseq from these cell populations to provide insight into factors influencing their cross-talk in health.

3- To evaluate the effects of cytokines on the differentiation potential of MSCs, as well as their ability to support bone resorption.

Eligibility
You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. The ideal candidate will have a background in immunology and cell or molecular biology.

The Faculty minimum requirements for candidates whose first language is not English are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply
To apply for this position potential applicants should initially contact the lead supervisor, Dennis McGonagle directly [Email Address Removed]

To apply for this scholarship applicants should complete a Faculty Scholarship Application form using the link below http://medhealth.leeds.ac.uk/download/3551/fmh_scholarship_application_2017_18 and send this alongside a full academic CV, degree certificates and transcripts (or marks so far if still studying) to the Faculty Graduate School [Email Address Removed]

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to [Email Address Removed] by no later than Thursday 25 January 2018.

Any queries regarding this project should be directed to Richard Cuthbert directly [Email Address Removed]

Any queries regarding the application process should be directed to [Email Address Removed]