Unwrapping the 3D genome to map autoimmune disease

This honours projects seeks to unravelling the chromatin interactome to map the genetic risk of type 1 diabetes.

Autoimmune diseases have a genetic risk: GWAS have identified more than 200 regions containing genetic variations linked to autoimmune disease risk but how these variations contribute to disease has remained elusive. Critically, more than 80% of the disease linked variations identified in genome wide studies are not located in the coding regions of genes.

Autoimmune diseases genetic risk affects CD4 T cell specific enhancers: Up to 60% of candidate autoimmune disease associated variants are localised to regulatory elements (enhancers) active in lymphoid cells. These variants may alter the expression of the genes normally controlled by enhancers in Treg and T conv cells Discovering the target genes controlled by these enhancers will therefore pin-point the critical pathways disrupted in Treg and Tconv cells in autoimmune disease.

It is now clear that enhancers acting over large distances are critical for controlling the cell-type- specific transcription of target genes. Up to 50% of enhancer regions, and do not interact with the nearest gene(s), but interact with promoters hundreds to thousands of kilobases away via DNA looping.

This project will use Chromatin Conformation Capture (3C, 4Cseq and Hi-C), reveal actual connectivity between regulatory elements containing genetic risk and their targets.

Professor Simon Barry

Supervisors

Professor Simon Barry

Co-supervisor: Tim Sadlon - Women's and Children's Hospital

Research area: Molecular immunology

Recommended honours enrolment: Honours in Molecular and Biomedical Science

Tagged in Honours projects - Molecular & biomedical science, Honours projects - Simon Barry, Honours projects - Tim Sadlon