Uncovering New Regulators of Gene Expression Using CRISPR and Genomic Tools

• PhD
• Honours

Precise control of gene expression is critical for normal development and homeostasis. When transcriptional control is lost, the dysregulation of gene-expression results in human disease, including cancer.

Our lab recently used genome-wide CRISPR screening, along with advanced genomic and molecular techniques, to identify and study new protein complexes that regulate transcription (Vervoort et al., Cell, 2021).

In this project, the students will use unbiased screening approaches, CRISPR-Cas9 gene editing, to discover novel regulators of transcription. The student will also explore how these regulators work using advanced genomics such as: ChIP-seq, RNA-seq, nascent transcription profiling among others.

This is a hands-on opportunity to contribute to cutting-edge research aimed at understanding and targeting the core machinery that controls gene expression.

Gene expression control is vital for health; deregulation causes diseases, including cancer. RNA Polymerase II (RNAPII) creates temporary RNA messages from DNA, instructing cellular processes, a process which is called transcription.

Cancer cells hijack RNAPII for aggressive growth and when control over the transcriptional process is lost, uncontrolled RNAPII activity may boost cancer growth.

We aim to identify how the transcription process is regulated and use this understanding to find anti-cancer therapeutics. These novel therapeutics are aimed at restoring transcriptional control and thereby halting tumor growth.

Our goal is to uncover more checkpoints, find novel targets, develop therapies, and positively impact patient outcomes.

From fundamental discoveries to translation!