Hasan’s team, the Single Molecule Imaging of Genome Duplication and Maintenance Laboratory, investigates tiny biological ‘machines’ which are responsible for copying DNA and making sure two daughter cells receive equal amounts of genetic material. 

By studying DNA replication with fluorescence microscopy and biochemistry, the lab aims to pinpoint how copying machines deal with barriers along the way. Understanding how these processes work in healthy cells can then shed light on how errors during replication can lead to cancer. 

Staying stable under stressful conditions

‘DNA replication stress’ is where the cell can’t fully copy its genetic material, caused by damage on the DNA or limited availability of proteins that make up the replication machinery. 

The new funding will allow Hasan’s team to use powerful imaging techniques to look at DNA replication stress in Xenopus frog eggs. They will first introduce lesions (areas of damage) into the DNA to understand whether the replication machinery can process and bypass these damaged sections. 

They will then capture a process called ‘replication fork reversal’ for the first time using live imaging technology. This process is where the replication fork, a Y-shaped structure that unwinds the DNA helix and creates two templates for replication, branches from a three-way junction into a four-way junction under replication stress, allowing areas of damage to be bypassed. Until now, it has not been possible to visualise this process within living cells. 

Finally, the team will investigate which components of the cell’s repair machinery restart DNA replication under various types of stress, and how all these components interact. 

By uncovering how the cell deals with stress during DNA replication, Hasan hopes to provide a better understanding of how cancer develops if these processes go wrong. 

Hasan said: 

I am incredibly excited to have secured a Wellcome Discovery Award. Our lab has been using cutting-edge single-molecule imaging methods to investigate how the machinery that replicates our DNA functions under normal conditions. With the new funding, we can now explore how this machinery responds to replication stress, a major cause of genome instability and a key driver of cancer. I am extremely grateful to the Wellcome Trust for this opportunity, and to all the past and present members of my lab whose work made this possible.

Wellcome Discovery Awards provide funding for established researchers and teams who want to pursue bold and creative research ideas to deliver significant shifts in understanding related to human life, health and wellbeing.