Doing the twist on damaged DNA – Simon Boulton wins the Paul Marks cancer research prize

Dr Simon Boulton in his lab at our London Research Institute

We’re happy to announce that our scientist Dr Simon Boulton has won the prestigious Paul Marks cancer research prize. It’s awarded by the Memorial Sloan Kettering Cancer Center in New York every two years to the brightest and best young scientists in the world, and he’s sharing it with Levi Garraway and DJ Pan.

We’ve funded Dr Boulton throughout his scientific career – except his post-doctoral work in the US – and he heads the DNA Damage Response lab at our London Research Institute Clare Hall Laboratory. We caught up with him for a chat to find out more about his life and work, and – perhaps surprisingly – discovered that his early brushes with science weren’t quite as successful as they are today.

Dr Boulton explains: “When I was at middle school, my science teacher told my parents ‘Make sure he doesn’t go into science because he’s no good at it’. Luckily, I then had a biology teacher who was passionate about the subject, and inspired me to pursue it for my degree.

“When I was a student at the University of Edinburgh, I discovered molecular biology. It was all quite new – this was the mid-nineties – and there were exciting papers coming out every week about genetic engineering and things like that. I became really fixated on it, and decided to go on to do a PhD.”

A taste for DNA damage

Luckily for Dr Boulton – just plain Simon back then – he was put in touch with an up-and-coming researcher called Dr Steve Jackson (now Professor) who’d just come back from working in the US at the University of California, Berkeley.

Dr Jackson set up a new lab in Cambridge at the Gurdon Institute, which is jointly funded by Cancer Research UK and the Wellcome Trust, focusing on how cells repair damage to their DNA. Unchecked DNA damage can lead to cancer, so understanding how it works – and what happens when it doesn’t – is vital if we’re to tackle the disease effectively.

Working in Professor Jackson’s lab sparked Dr Boulton’s interest in DNA damage and repair, which is still the area he focuses on with his own team. But after completing his PhD, he needed a change. The next destination was Harvard Medical School, where he worked on the cell cycle – the fundamental biological ‘engine’ in all living cells that makes them multiply. Yet he drifted back towards his earlier passion for DNA repair.

While at Harvard, Dr Boulton joined forces with another researcher, Marc Vidal, who was carrying out large-scale genetic experiments on tiny nematode worms called C. elegans. Together, they carried out a huge study to identify DNA damage genes in the worms, many of which turned out to be related to human genes involved in cancer.

The next step was to find out how they worked and what they were doing.

Worming a way back to the UK

In 2002, Dr Boulton returned to the UK, where he had been offered the chance to set up his own lab at our Clare Hall campus, part of the prestigious Cancer Research UK London Research Institute.

“It was a great opportunity to come to Clare Hall. I’ve always been open to approaching a problem from a new perspective, and not being afraid to try something new. When I set up the lab, I wanted to go across different model organisms to answer questions about DNA repair, using worms, yeast and mammalian cells. We also use mouse models for the things you simply can’t do with worms, such as the impact of DNA damage on tumorigenesis – the process that leads to cancer.”

Over the past decade, Dr Boulton and his team have made a number of significant discoveries about some of the genes and molecules involved in repairing damage to DNA. In particular, his work has focused on a type of damage known as double-strand breaks, where the DNA ‘ladder’ is completely severed.

Double-strand breaks can be caused by a range of things, such as ionising radiation (e.g. X-rays), or simply stuff going wrong as a cell copies its DNA when it divides. But the breaks are extremely dangerous, as they can lead to the wrong bits of DNA getting stuck back together again when they’re repaired. This wreaks havoc within a cell, with important genes ending up in the wrong place where they can’t be controlled correctly.

RTEL me a story

Perhaps Dr Boulton’s biggest contribution to the field of cancer research has been uncovering and understanding the role of a molecule called RTEL1. This protein plays a vital role in controlling double-strand break repair.

He explains: “It acts a bit like a ‘reverse gear’ for the repair machinery – it allows cells to undo situations where they’re about to repair damage incorrectly. But there has to be a balance, as if there’s too much RTEL1, then it takes apart productive repair events and cells can’t repair their DNA properly. But if there’s not enough then the wrong DNA ends get ‘glued’ together, which is also very serious.”

But there have been many other discoveries too – Dr Boulton also studies molecules called helicases, which untwist and ‘unzip’ DNA so it can be copied and repaired, and has made significant findings about several of them.

He and his team are now starting to make chemicals that can block some of the molecules they’ve found, with the hope of developing new drugs for cancer. But it’s taken eight or nine years of painstaking hard work to get to this point.

Colleagues and friends

It’s undeniable that the environment of the London Research Institute has been important for Dr Boulton’s success. He says: “Cancer Research UK has brought together some of the top people in the world here at Clare Hall. We can do science that’s very difficult to do anywhere else, underpinned by core funding from the charity.

“Even in the US, researchers are struggling. I think Cancer Research UK has done a remarkable job of continuing to fundraise and fund research, despite the economic crisis. And it’s the charity’s supporters that have been essential for this.”

Like most scientific research today, his work is highly collaborative – something that’s been helped along the way by his friends and colleagues. “Steve West has been like my scientific ‘father’ – a friend, mentor and colleague. The thing that keeps me motivated is the people I work with. I’m privileged to have a lab full of 14 smart people – scary smart! – and they’re fantastic.

“It doesn’t feel like work – it feels more like a hobby and I love it, although one problem is that I don’t switch off. Now I have kids they demand my full attention when I go home, but I’ll still wake up in the middle of the night with an idea for an experiment.”

Onwards and upwards

As for the future, Dr Boulton’s appetite for research and finding new ways to tackle cancer shows no signs of diminishing. He says: “What motivates me and keeps me going with science is that you think you know something, and then you start digging and realise you don’t know anything. Things change very rapidly, which is what makes it so fun. Being in a great environment like the London Research Institute, or the Francis Crick Institute – where we’re moving to in 2015 – is really important.

Dr Boulton will be moving into the new Francis Crick Institute

“I’m excited by the potential for closer interactions with other Cancer Research UK scientists who will be moving there, as well as the people coming from other organisations. You can learn so much talking to developmental biologists, neurobiologists, immunologists and so on – people working in other fields that help to shed light on your own work.”

By winning the Paul Marks prize, Dr Boulton joins the ranks of the brightest young cancer researchers in the world, including fellow Clare Hall resident Dr John Diffley.  We’re immensely proud to have supported him for much of his scientific journey so far, and pleased he didn’t listen to his first science teacher. We look forward to seeing what he discovers in the future.

Kat