Time flies

Joining a new organisation and building your research team during a pandemic isn’t ideal but new group leader Dr Ian McGough is pleased he’s found his niche, and gorgeous trail running routes, alongside a very warm welcome. Here he explains his passion about flies as he works to answers unexplored questions about morphogens in ageing.

And he had his flies – thousands of them – for company. A passionate drosophilist, Ian’s arrival signals the return of flies to the Institute after an absence of some years. Many signalling pathways were first discovered in Drosophila and, despite being eclipsed by mouse models in many fields, flies remain powerful research tools – provided you ask them the right questions.

Ian’s research questions concern morphogens – signalling proteins that play a critical role in development and act as the blueprint for tissue formation. When morphogens are secreted, the signalling molecules form a gradient, meaning that some cells receive a lot of the signal while others get only a little. “This is the way that morphogens can pattern whole tissues,” he explains.

Although there are many morphogens, Ian’s lab focuses on two: Wnt (pronounced wint) and Hedgehog. As well as directing development, morphogens maintain healthy tissue structure and function in adulthood by regulating how stem cells repair, replace and regenerate lost or damaged cells. And while their role in development is well studied, much less is known about how morphogens like Wnt and Hedgehog work in adulthood and their involvement in the decline in tissue renewal that happens during ageing. “I’m interested in the gradients of the morphogens in adulthood, and in particular how they’re affected in ageing. Because as we age, these tissues stop renewing. It’s one of the things that happens with ageing, this failure of tissues to rejuvenate." Carving out your own scientific niche requires the combination of curiosity, assessing the lie of the land, and carefully selecting the tools of your trade. Recognising an opportunity,

Ian is set to explore this less-charted ground of what happens to morphogens with age. Are they driving this decline in tissue renewal as we age? A couple of recent papers suggest the answer is yes, and that decreased morphogen signalling in the intestine is responsible for the loss of the vital stem cell pool needed for tissue maintenance.

Before arriving at the Institute, Ian worked at the University of Bristol and the Francis Crick Institute in London, where he solved a question that had puzzled Wnt researchers for decades, namely how a signalling protein with fatty, water-hating parts could diffuse well enough to act via a concentration gradient.

Now, his lab wants to answer two new and important questions: how do Wnt and Hedgehog work at a mechanistic level, and how do the components of these pathways change with age? “We want to know how they work because morphogens are critical in development and ageing, but we can’t answer the second question without knowing the answer to the first,” he says.

While his colleagues at the Institute know him as a successful scientist and former UK Young Cell Biologist of the Year, they may be unaware that some of his grit comes from Gaelic football. “It’s a  weird mix of football and basketball, but what I love about the sport is how physical it is; you man mark your opponent, meaning there are 15 individual – often quite aggressive – battles in each game. It also means you need to be mentally strong,” says Ian.

Running his new lab and experiments should offer a more straightforward challenge. He’ll be using Drosophila – housed in a new temperature-, humidity- and light-controlled fly room – to study Wnt and Hedgehog’s role in ageing. “Drosophila is my model for the ageing work because the fly intestine declines with age – stem cells over proliferate, the gut gets leaky,” he says.

As a signaller and an outdoor type, Ian and the Institute play to each other’s strengths. “It’s a great place for signalling, I can just walk down the corridor and talk to leading experts in related areas and perhaps together we can tease things apart. It’s also a match for the direction I want to take my lab – into developmental signalling pathways but in an adult and an ageing context. And with Wnt and Hedgehog, I bring something new to the place,” he says. “I’m not a museum or theatre-goer so London was wasted on me. The grounds here are amazing, there’s 5km of trail running just over the bridge, so for me, the Institute is just perfect.”