Deciphering the genetics of common immune diseases
Gosia is a group leader at the Wellcome Sanger Institute in Cambridge where her group combines immunologic assays and genomic approaches to identify and understand the role of genetic variants in modulating the immune system and in predisposing individuals to autoimmunity. Particularly, her group studies the role of disease associated variants in regulating the adaptive immunity. During her PhD at Groningen University in the Netherlands, Gosia was a co-lead analyst of GWAS for coeliac disease which identified 57 risk variants. In her postdoc at the Broad Institute she developed statistical methods that integrated disease associated variants with epigenetic marks to identify disease pathogenic cell types.
Using broad genomic toolkit, from profiling chromatin landscape, through to measuring gene expression in bulk and at the single cell level, we are dissecting the role of immune disease variants in different contexts of CD4 T cell functions. In my talk I will present results from two of our recent studies.
We stimulated T cells and macrophages in the presence of thirteen different cytokine cocktails linked to immune diseases and profiled active enhancers and promoters. We developed a new statistical method (CHEERS) to identify SNP enrichment across cell states. Our results point towards the role of immune disease variants in early rather than late activation of memory CD4+ T cells, and with modest differences across polarising cytokines.
In the second project we mapped genetic regulation (QTL) of gene expression and chromatin activity in regulatory T cells (Tregs), cell type critical for immune homeostasis. We identified 123 loci where Treg QTLs colocalized with immune disease variants and showed that these effects resulted in impaired suppressive function of Tregs.
Our results suggest that a proportion of immune disease variants can lead to escalated immune response by 1) promoting early activation of memory T cells and 2) impairing the suppressive capacity of Tregs, therefore leading to deregulation of CD4 T cell activation circuitry.
3 July 2019, 13:00 (Wednesday, 10th week, Trinity 2019)
Wellcome Trust Centre for Human Genetics, Headington OX3 7BN
Dr Gosia Trynka (University of Cambridge)
Wellcome Trust Centre for Human Genetics
Isabel Schmidt (University of Oxford, Wellcome Centre for Human Genetics)
Members of the University only