Inhibitor of DONSON-GINS interaction as an experimental tool and potential anticancer strategy University of Birmingham in United Kingdom

Application deadline - midday (GMT) Friday 10 January 2025

Inhibition of initiation of DNA replication is an attractive and promising anticancer strategy. We have identified a new peptide that inhibits interaction between key replication initiation proteins and inhibits initiation of DNA replication. The aim of this project is to characterise the mechanism of action of this peptide and determine its potential as a research tool but also as a potential anticancer compound. This is an interdisciplinary project allowing the student to develop skills across a whole portfolio of dimerent techniques. We will determine the kinetics of inhibitor interaction with target proteins using in vitro biophysical assays. We will characterise the molecular mechanism of action of the inhibitor during DNA replication using biochemical approaches in cell free system of Xenopus laevis egg extract. We will use the compound as a tool to freeze the replication machinery at the initiation stage and determine its structure using cryo electron microscopy (cryo-EM). Finally, we will assay its therapeutic potential through testing its emects on viability and proliferation potential of cancerous and non-cancerous cell lines. Altogether, these 4 angles of investigation will give us a comprehensive understanding of the action and usefulness of our new inhibitor.