Image: Chromosomes and their telomeres (visualised in red). Credit: Thomas Ried, NCI Center for Cancer Research
You might not have heard of telomeres but they’re incredibly important – they are the caps that protect the end of chromosomes. They work like the plastic tips that stop your shoelaces from fraying.
All cancers alter telomeres in order to survive, so by doing ‘basic’ research to try to understand how telomere replication and processing works, Max and his team hope to identify possible new ways to target and treat cancer.
Having joined the Division of Cancer Biology in October 2019, Dr Max Douglas is now one of the newest Team Leaders at the ICR. I met him at our Chester Beatty Laboratories in Chelsea, where he told me more about his work.
A focus on DNA replication
Max studied for his PhD in biochemistry and cell biology at the University of Cambridge. He then joined Dr John Diffley’s team in London’s Clare Hall Laboratories – which later became part of the Francis Crick Institute – where he focused on studying the early stages of DNA replication.
At the Crick, he helped establish in detail how a protein complex – called the CMG replicative helicase – that helps unwind DNA during replication, is assembled and activated.
Now at the ICR, Max leads his own research team studying DNA replication – but in the context of telomeres and cancer.
“My main project is to rebuild telomeres in the lab and then unpick how they work – how they are replicated and how they are processed. This knowledge is generally useful, but we will focus on studying it in the context of cancer,” explained Max.
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Unravelling the mystery
When a cell becomes cancerous, it divides more often – and every time it divides, its telomeres become shorter and shorter. Once there is no telomere left, the DNA unravels, like a shoelace fraying, and the cell dies. This eventually happens in most healthy cells – telomeres shorten over time until cell division is no longer possible, leading to cell death.
While this loss of telomere protection can cause cancer cells and healthy cells to die, it can also lead to a state of genome instability that helps cancer survive and spread.
We also know that cancer cells can escape death by making telomerase, an enzyme that prevents telomeres from getting short. Certain cells in our body, such as stem cells, are able to divide over and over again thanks to telomerase. Cancer cells take advantage of this enzyme and hijack it to maintain telomere length – which enables them to continue to divide and spread.
In other words, telomeres seem to play a role in the death of cancer cells – but they’re also crucial for their survival. However, the molecular steps that guide telomere replication and processing remain poorly understood.
By using genetics and replicating cellular processes in a test tube, through a technique known as reconstitution biochemistry, Max and his team hope to better understand how telomeres are processed, and how they are inherited from one generation of cells to the next.
If Max and his team can dissect how telomeres work and clarify their link to cancer, maybe we’ll figure out new ways to treat it.
‘An institution with a mission’
His research might seem quite distant from the clinic, but Max knows he belongs at the ICR, which has an exemplary track record in making discoveries that ultimately benefit people with cancer.
“I really value the ICR’s commitment to doing basic, laboratory science. Good basic science is necessary to understand cancer, and the ICR values that. Here, I can figure out how to use my findings to benefit people, and that, in turn, will also hugely benefit my work,” Max said.
“I feel very lucky to work at an institution with a mission, being able to do what I love while getting opportunities to make discoveries that could help people.”
As a new Team Leader, Max is currently the only member of his team but a higher scientific officer will be joining this month, as well as a post-doctoral training fellow, who will be joining in March. They will also start recruiting for a PhD student. As he told me, he can’t wait for the new team members to join him in January.
“I’m excited to supervise other people for the first time. I want to build a strong team and a good environment for them to thrive in.”
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