Effect of genetic variants on immune cell function
Research type
Research Study
Full title
Effect of genetic variants associated with risk for inflammatory disease on immune cell phenotype and function
IRAS ID
243558
Contact name
Carl Anderson
Contact email
Sponsor organisation
Genome Research Ltd
Duration of Study in the UK
6 years, 0 months, 0 days
Research summary
Crohn’s disease and ulcerative colitis are two common forms of inflammatory bowel disease (IBD), which is characterised by chronic inflammation of the gastrointestinal tract. Primary sclerosing cholangitis (PSC) is a rare, progressive disorder leading to bile duct destruction. Approximately 70% of PSC patients have concurrent IBD. IBD and PSC are thought to result from an interaction between environmental factors (especially the microbiome), the host immune system and the epithelial barrier in genetically susceptible individuals. The lack of treatments for both IBD and PSC are due to a lack of disease understanding.
Genetic association studies have identified 215 risk loci for IBD. The majority of these susceptibility loci lie in regions of the genome that do not code for proteins. As such, the relative contribution to disease development is still to be determined.
The cells of the immune system are very important during infection and/or inflammation. An abnormality in immune system regulation is central to the development of PSC and IBD. In this project we will analyse how disease risk loci contribute to inflammatory disease by investigating whether they affect immune cell function.
No participants will be recruited to this study, we will use human immune cells from fully consented anonymised adult healthy blood donors (unlinked) purchased from consented adults through services including, but not limited to, NHS Blood and Transplant (NHSBT). The genomes from these cell will be edited using CRISPR-Cas9 technology and the effects of these changes analysed by a number of cellular assays, including extracting the DNA/RNA to find the genetic profile (genotype) of the donors and the expression of genes.
This approach will allow us to determine the effect of many disease risk variants on immune cells and potentially identify new therapeutic disease targets and/or pathways.REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
18/YH/0115
Date of REC Opinion
26 Mar 2018
REC opinion
Favourable Opinion