CDK18-dependent regulation of the DNA damage response

Understanding how cells and tissues age, and how this is linked to an ability to detect and repair DNA is a fundamental biological question. The regulatory mechanisms through which cells respond to stress and disease are increasingly well understood, and the central role of protein phosphorylation is widely appreciated. However, making sure that we understand the mechanisms by which protein kinases regulate these process remains an important challenge. Indeed, it appears clear that cells are subject to 'critical periods' during the cell cycle in their lifespan when they may be particularly susceptible to DNA damage. Understanding these mechanisms will be informative to help understand potential timings for molecular or lifestyle interventions aimed at promoting a healthy life. To meet these challenges requires new and innovative collaborative strategies and a new type of biological scientist working at the interface between biophysics, cell biology and proteomics. This is a joint project between Newcastle and Liverpool combining training in protein kinase biology and phosphoproteomics. The University of Liverpool plays a leading role in developing cell and MS-based resources for proteomic analysis. However, to be really powerful, phosphoproteomics (the study of cellular protein phosphorylation) requires carefully manipulated cell systems, and this is best achieved using specific cell permeable small molecules, which can rapidly and reversibly inhibit protein kinases. This project will initially test the hypothesis that chemical Cyclin Dependent Kinase 18 (CDK18) inhibitors can be employed to reveal CDK18-dependent phenotypes in cells. By working with our partners in Newcastle, we will evaluate the specificity of CDK18 inhibitors, ruling out ‘off-target’ effects using CDK-wide screening assays. Subsequently, we will employ specific compounds to uncover phosphorylation targets and transcriptional pathways regulated by CDK18. This will open up new research into cellular biomarkers of DNA damage, bringing about new industrial opportunities in the future.

For further information see the website: https://www.liverpool.ac.uk/integrative-biology/

To apply:
Please submit a full CV and covering letter directly to [Email Address Removed]