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Single-Cell Genomics to Predict the Cellular Etiology of Autoimmune Risk Loci

Hamish King, PhD, Laboratory Head in the Epigenetics and Development division at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia
Monday, November 27, 2023
3:00 pm - 4:00 pm
Hamish King
CBB Monday Seminar Series

To fight and remember infections, B cells in our immune system must undergo maturation in the germinal centre reaction. Errors in this process can lead to either defective immune responses (immunodeficiency) or autoimmune diseases (e.g. rheumatoid arthritis, lupus, multiple sclerosis). Many questions remain about the dynamic cellular states involved in both normal and disease-related GC B cell phenotypes, including the gene regulatory networks that underlie key cell fate decisions. Using single-cell transcriptomics and epigenomics we recently discovered that many non-coding GWAS variants linked with >21 diverse autoimmune diseases exhibit their greatest regulatory potential in GC B cells, meaning that to understand the genetic causes of many autoimmune diseases we must investigate the regulatory function of these non-coding autoimmune risk loci in this specific cell type. I will present current efforts in the King lab to model the human germinal centre reaction ex vivo and experimentally test the function of non-coding genomic regions using single-cell CRISPR screening technologies.