WEHI Wednesday Seminar hosted by Professors Marnie Blewitt & Anne Voss
Hamish W King, PhD
Laboratory Head, Epigenetics & Development division – Healthy Development & Ageing Theme, WEHI
Genetic and epigenetic regulatory mechanisms in human B cells
Join via SLIDO enter code #WEHIWEDNESDAY
Including Q&A session
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. Here I will present my work generating a comprehensive roadmap of human B cell maturation with single-cell transcriptomics and epigenomics and how we used this resource to reconstruct gene expression and transcription factor dynamics during B cell activation. We discovered that many non-coding GWAS variants linked with >21 diverse autoimmune diseases exhibit their greatest regulatory potential in germinal centre 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. I will also introduce other exciting projects from the lab investigating the molecular function of immune-specific chromatin regulators and dynamic epigenetic changes that occur in germinal centre B cells.
Hamish King completed his undergraduate at Flinders University in Adelaide, before moving to the United Kingdom to undertake his PhD in molecular epigenetics at the University of Oxford with Prof Rob Klose. While there he studied how gene expression is regulated by chromatin-modifying complexes, and how sequence-specific transcription factors cooperate with chromatin remodellers to access and bind the genome. Following his PhD, Hamish was a Sir Henry Wellcome Postdoctoral Fellow in the lab of Dr Louisa James at the Blizard Institute, Queen Mary University of London, where he studied the transcriptional and epigenetic networks that determine human B cell identity and function. Hamish joined WEHI as a Laboratory Head in the Epigenetics and Development Division in February 2022, where his team aims to understand the molecular mechanisms that underpin global and locus-specific control of gene expression in immune-mediated diseases.