Functional epigenomics in human B cells

Functional epigenomics in human B cells

Project details

B cell maturation in the germinal centre is essential for high quality antibody responses and long-term immune memory. Errors in gene regulation during this process are also closely linked with B cell-related pathologies, including immunodeficiency, autoimmunity and cancer. However, many of the mechanisms that control gene expression in human B cells remain poorly understood, and this is especially true for chromatin-based epigenetic pathways that act through modification of DNA and histones.

This project will examine the mechanisms by which chromatin-associated proteins interact with the B cell epigenome to regulate gene expression. This will involve a combination of advanced CRISPR/Cas9 genome engineering, functional genomic assays (ATAC-seq, RNA-seq, ChIP-seq) and single-cell transcriptomics, as well as providing an opportunity to train in both experimental and computational genomics.

About our research group

The King lab will join WEHI in March 2022, and aims to understand how defects in the epigenetic control of gene expression are involved in human disease. Building on detailed single-cell transcriptomic and epigenomic profiling of the human immune system, the King lab is currently seeking to understand 1) how immune-specific chromatin-based mechanisms regulate gene expression, 2) whether autoimmune-associated genetic risk loci disrupt regulatory function of enhancers, and 3) if disease-specific epigenomic networks exist in autoimmunity. 

To achieve this, the lab uses in vitro cell cultures and ex vivo immune organoids as model experimental systems, and integrates this with analysis of ‘real world’ patient single-cell multi-omic datasets to provide translational insights into how epigenetic dysregulation in the immune system is linked with disease.

 

 

Email supervisors

 

Researchers:

Dr Hamish King
Dr
Hamish
King
Epigenetics and Development (from 2022)

Project Type: