Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Project Overview:

Ankylosing spondylitis (AS) is a common form of spinal inflammatory arthritis affecting about 200,000 individuals in the UK. Twin studies indicate that AS is highly heritable and it is likely that there are more than 100 genes involved. Among these associated genes, one is RUNX3 (involved in lymphocyte maturation). We have recently demonstrated that AS-associated single nucleotide polymorphisms (SNPs) upstream RUNX3 genomic locus have an effect on the function and the regulation of the gene.

Our primary goal is to decipher the precise mechanism(s) through which AS-associated SNPs at the RUNX3 locus alter gene expression and transcription in different cell types. This will help us to evaluate more completely the role of the RUNX3 locus as a pivotal epigenetic mechanism for the development of AS. We will investigate its 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 gene regulatory networks specifically 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)