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Project Overview:

Ankylosing spondylitis (AS) is a spinal inflammatory arthritis affecting about 200,000 individuals in the UK. It is a genetic disease with more than 100 genes involved. One of the genes is RUNX3 (involved in lymphocyte maturation). We have recently demonstrated that single nucleotide polymorphisms (SNPs) at the RUNX3 locus may have an effect on the function and the regulation of the gene.

We aim to decipher the precise mechanism(s) through which these RUNX3 SNPs alter gene expression and transcription in different cell types, and how is their impact on AS. We will investigate RUNX3 role in the regulation of immune function by applying several cellular and molecular biology techniques that we have developed in our lab.

These results will allow us to define the molecular mechanism associated with AS. Our final goal is the investigation of potential pathogenic pathways and the development of interventional reagents as part of our early phase drug discovery programme for AS. 

The approach described in relation to the RUNX3 locus is relevant to the investigation of many other loci that are genetically associated with AS.

 

Training:

Our group has successfully established different techniques in the lab. We routinely apply statistical methods to identify primary genetic associations, perform primary cell culture, electrophoretic mobility shift assay, chromatin immunoprecipitation, DNA/pull-down etc. Our group studies a range of fundamental and interlinked cell biology questions and will be involved in interacting with clinical members (Nuffield Orthopaedic Centre).

 We also have close collaborations with:

  • Professor Bowness group, immunology of Ankylosing Spondylitis;
  • Professor Oppermann group (Molecular biology, drug development and chemical biology);
  • Dr Fischer (Mass Spectrometry, within the Target Discovery Institute)

The successful candidate will have the chance to acquire skills in all these different areas.

Relevant Publications (max 5)