Dr Henry Lee-Six

Wellcome Sanger Institute, Cambridge

Title of the project: Mutational landscape of normal colon

Project Supervisor: Professor Sir Michael Stratton

I have just finished the research component of the Cambridge MB/PhD  programme. When I began my PhD, I was looking for a project that had the potential to make a real difference to patients’ lives while also revealing new and exciting biology. I wanted to try to understand how cancer happens through the lens of Darwinian evolution. Working on this project with Mike Stratton allowed me to do exactly that.

All cancers were once normal cells. Normal cells become cancerous through the acquisition of particular typos in their DNA code (or mutations) that cause them to behave selfishly, dividing and outcompeting their normal neighbours until they have formed a tumour.

It is the mutations that occur in normal cells, therefore, that set a normal cell on the road to cancer. In the human large bowel, although fledgling and fully-fledged cancers have been heavily investigated, we know remarkably little about the processes that cause mutations in normal cells. In an attempt to describe them, we dissected hundreds of microscopic samples of normal human bowel with a laser and sequenced them to read their DNA code. We found that many different processes operate in normal human bowel, and that there was a remarkable diversity in the processes active between different people, and even between different biopsies from the same person.

We hope that future research will pinpoint the agents responsible for each of these mutational processes, allowing us to avoid them or develop drugs to protect us against them, and so prevent bowel cancer from occurring in the first place.