Analysis of non-coding gene regulatory element function in the human immune system

• Honours
• PhD

Non-coding DNA regulatory elements are essential for regulating gene expression levels within cells and genetic variation at these loci can disrupt normal gene expression control, potentially leading to dysfunctional cell states and disease.

This project aims at identifying non-coding DNA regulatory elements that are active during human B cell maturation and investigating how these regulatory elements may be disrupted in immune-mediated diseases like autoimmunity or immunodeficiency.

The project may involve the bioinformatic analysis of single-cell genomic datasets to map dynamic gene regulatory elements that may control gene expression in human B cells, experimentally testing the function of these non-coding gene regulatory elements, and/or introduction of non-coding genetic variants with Cas9-Prime Editing to determine their consequences on target gene expression.

The King lab studies how defects in the control of gene expression are involved in human immune-mediated diseases. 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profiling of the human immune system (King et al 2021a Science Immunology, King et al 2021b Science Immunology) and unpublished high-throughput CRISPR activation screens in primary human B cells, we are a small and dynamic team focused on discovering fundamental mechanisms of gene regulation in the immune system.

The King lab uses both experimental and bioinformatic approaches, and team members are encouraged to develop experience in both areas. Prospective applicants should ideally have some experience and understanding of gene regulation, chromatin biology, and genomic technologies (e.g. RNA-seq, ChIP-seq, CUT&TAG).