Understanding the function of the DNA helicase RECQL4 in normal and cancer biology
This project aims to understand the pathways and interactors that normal and mutant RECQL4 engages in cells. We know that mutations in RECQL4 that cause protein truncation are a cause of the rare familial cancer syndrome Rothmund-Thomson Syndrome (RTS). We know that RECQL4 is essential for cell viability and proliferation, but we have a limited understanding of the pathways regulated by and regulating RECQL4 particularly in the context of mutant RECQL4.
We have used forward genetics to identify new loss of function mutations that can modify the cellular phenotypes of mutant RECQL4. These pathways are poorly understood. We will use a combination of cell line studies and in vivo genetics to understand how these loss of function mutations can rescue cells expressing mutant RECQL4. This will identify mechanisms that control cell division and also potentially identify therapeutic approaches to RTS and cancers with somatic RECQL4 mutations.
We use mouse models, cell culture, molecular and biochemical techniques to model mutation or loss of RECQL4 to better understand how this impacts cells. This project would characterize new players in this pathway identified in a genome-wide CRISPR/Cas9 screen.
Techniques – flow cytometry, genetics, cell culture, molecular biology, biochemistry, CRISPR/Cas9, genome-wide screening, protein interaction mapping, bioinformatics
Dr Monique Smeets
Prof Carl Walkley
Cancer & RNA biology
For further information about this project, contact: