Adapting to change and challenge

Understanding how things work underpins the Institute’s past, present and future. Dr Simon Cook, Institute Director and head of the Signalling programme, explains why he’s an evangelist for discovery research, how this quest for understanding is reflected in the Institute’s science, its people and the ecosystem of the Babraham Research Campus, and looks ahead to the next four years’ work.

In building his case for discovery science, Dr Simon Cook need look no further than the Signalling programme he heads at the Institute he now leads. “If you look at advances over the last 40 years in understanding the molecular basis of cancer, they have closely paralleled our understanding of the molecular basis of signalling pathways: one has often led to discoveries in the other,” he says.

Signalling refers to the processes which enable our cells to respond to changes in their environment, from hormones and growth factors to radiation and ageing. At the cellular, tissue and organism level, we are constantly adapting to change and challenge. That’s why understanding how signalling controls cell behaviour is critical to understanding lifelong health – and how to improve it.

Cancer is a case in point. “Signalling pathways, or the genes that encode proteins making up these pathways, are often mutated in cancer. These mutations lead to pathways being switched on at the wrong time.

As a result, cells receive signals telling them to grow and divide when they shouldn't, which can lead to the initiation of cancer,” says Cook. “Understanding how this drives cancer and recognising how particular components are mutated underpins our ability to develop drugs to inhibit these pathways.”

Since 2019, Cook has overseen a strategic shift in the Signalling programme, introducing new faces including Dr Hayley Sharpe working on signalling by reactive oxygen species and Drs Rahul Samant, Ian McGough and Della David to strengthen the Institute’s ageing and proteostasis research. “We have recruited group leaders with a forte in ageing, cell senescence and proteostasis, and they have brought with them a wider range of model organisms such as worms and flies, short-lived species which are important in ageing research,” he explains.

This re-engineering of the Signalling programme will drive discoveries in proteostasis and feed into practical, translational benefits, including new drug targets, something that the Institute is adept at. Today, the Institute is the hub of the Babraham Research Campus which—with more than 60 companies and 2,000 employees—creates the right conditions for discovery research and business to come together, accelerating innovation and strengthening links between academia and the commercial life sciences sector.

The Campus began life 25 years ago with the retrofitting of an old barn. “The director then, Dr Richard Dyer, had this vision,” Cook recalls. “He looked at other science parks and saw they were dominated by large, established companies, but there was nowhere nurturing small startups, so he made that happen. The Campus has been a stunning success because the Institute is behind it. There's real synergy of effort between the Institute and Campus companies, which is a delight to see.”

The Signalling programme has a history of working with pharmaceutical companies, and the benefits are mutual. Industry empowers the Institute’s work through access to early-stage probe compounds from drug discovery. And by sharing knowledge of signalling pathways with pharma giants including AstraZeneca and GlaxoSmithKline, the programme’s discovery research paves the way for new drugs. “By giving early insights into the impact of inhibiting particular pathways, our research has supported drug-discovery programmes in pharma and biotech,” says Cook.

The same happens on Campus, where daily interactions between Institute and biotech strengthen the science, the scientists and the community. “The Babraham Research Campus is unique. Many science parks exist, but ours has a world-leading research institute at its heart,” he says. “We have a community where group leaders in the Institute have collaborative PhD projects with Campus companies, they use our science facilities, they rub shoulders with our scientists in the coffee queue, and that leads to grant applications. It makes for a very special place.”

All these ingredients—from new directions, tools, faces and collaborations—fuel Cook’s excitement for the future. “Recognising our existing strength in proteostasis provided an opportunity to build on a strategically important area in ageing research,” he says. “Understanding the mechanisms of proteostasis and how this fails in ageing and neurodegenerative diseases remains fundamental to finding new drug targets. I think there’s a real chance to understand the defects that drive protein aggregation in ageing and then identify ways to address this.”

The Institute’s core facilities are future focused too. “The mass spectrometry capability here is giving us a proteome-wide understanding of how proteostasis declines with age. Every time you open a journal there’s a new technique being developed to look at proteostasis in even more detail. It’s a really exciting time,” Cook concludes. “It’s easy to think discovery has all been done, we just need to translate. But when you stop doing discovery bioscience, the pipeline stops. So I remain an evangelist for discovery research.”