B cell maturation is essential for high quality antibody responses and long-term immune memory. Errors in gene regulation during this process are 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 regulate gene expression, and how this can go wrong in immune disease. Recently we have established novel methods to modulate gene expression in human immune cells, and this project will focus on new applications of these technologies. Other available methods in the lab include advanced CRISPR/Cas9 genome engineering, functional genomic assays (ATAC-seq, RNA-seq, ChIP-seq) and single-cell transcriptomics.
The King lab studies how defects in the control of gene expression are involved in human disease. Building on our recent detailed single-cell transcriptomic and epigenomic profiling of the human immune system (King et al 2021a Science Immunology, King et al 2021b Science Immunology), we are a small and dynamic team focused on discovering fundamental mechanisms of gene regulation in the immune system.
We work closely with immunologists to access patient tissues to increase the relevance and translational impact of our research. The King lab uses both experimental and bioinformatic approaches, and team members are encouraged to develop experience in both areas.