The T cell receptor in Health and disease

Lead Supervisor

Prof Andrew Sewell, Cardiff University (http://www.tcells.org/scientific/andysewell/)

Co-supervisors

Dr Sasch Ott, Warwick Systems Biology Centre (http://www2.warwick.ac.uk/fac/sci/systemsbiology/staff/ott/)
Dr Tom Connor, Cardiff University (http://www.cardiff.ac.uk/people/view/81141-connor-thomas)
Dr Meriem Attaf, Cardiff University (http://www.tcells.org/scientific/meriemattaf/)

Project Description

T lymphocytes and the receptors they bear at their surface are a critical component of the immune system. . The αβ T cell receptor (TCR) enables T-cells to distinguish ‘self’ from ‘non-self’ and choreograph immune attack on pathogens and cancerous cells. This remarkable receptor can theoretically exist in over 1,000,000,000,000,000,000 different forms (1) and acts as the ‘Swiss Army Knife’ of the immune system (2). Our TCRs are made somatically by gene rearrangement. This process generates several million unique TCR sequences in any individual collectively termed “the repertoire”. No two individuals, even if they are genetically identical, will have the same repertoire (hence even identical twins can be discordant for autoimmune diseases).
At the functional level, T cells orchestrate virtually all known immunological processes, including immunity against foreign pathogens and tumours, graft rejection, autoimmunity, allergy and hypersensitivities. Understanding how TCRs are generated and maintained throughout life is therefore bound to become a very important research area in future medicine and diagnostics. We believe that diseases can be diagnosed or predicted from TCR sequencing.

The primary research focus of this project is to dissect the genetic forces that govern the assembly and the maintenance of the mature repertoire in different settings, including:

- Healthy twins
- Cancer-specific responses
- Autoimmune responses (chronic diseases such as type 1 diabetes and ankylosing spondylitis)

This will be done at the molecular level, using high-throughput sequencing of sorted T cell populations. This “Systems” approach will undoubtedly shed light into the genetic and the environmental factors at work to shape the TCR repertoire in health and disease (3).

The Research Group

The Sewell group (www.tcells.org) works on all aspects of T-cell biology (immunity to infection, autoimmune disease, transplant tolerance and cancer immunotherapy) and has current research funding in excess of £6 million. Our group maintains strong links with industrial partners who deliver immunotherapies to patients in clinical trials (e.g. Immunocore Ltd and Adaptimmune Ltd) and also to Immudex who specialise in T-cell detection technologies.

Previous Students

Our students do well. Two Sewell group PhD students were students of the month at FindAPhD.com in 2012 http://www.findaphd.com/student/news.aspx?id=00227 Several previous Sewell PhD students now have independent fellowships. Former student Linda Wooldridge (2005) was recently awarded a professorship in Bristol. Five former Sewell PhD students now work with our industrial partners so a PhD with us can also be a good steppingstone to a career in industry.

What We Are Looking For

The successful student will join a frontline research grouping in the Institute of Infection and Immunity at Cardiff University School of Medicine where Prof. Sewell is Research Director. You must be enthusiastic, self-motivated with the highest grades. We expect you to have a good degree in a relevant subject. An interest in Big Data analyses and Systems Biology and experience in Molecular Biology would be an added bonus.

For further information please see the below links:

The Institute of Infection and Immunity: http://medicine.cf.ac.uk/infect-immun/
Students in the Institute: http://medicine.cf.ac.uk/infect-immun/pgr/
South Wales Immunology Group: https://www.immunology.org/south-wales
Why you should visit South Wales: https://www.immunology.org/south-wales/life
Cardiff Ranked 5th in the UK for research excellence: http://www.cardiff.ac.uk/research/impact-and-innovation/quality-and-performance/ref-2014

Tom explains Big Data and Cloud Infrastructure for Microbial Genomics: https://www.youtube.com/watch?v=fZhw5FMLUjM

Cardiff University reserves the right to close applications early should sufficient applications be received