In search of patterns

How to solve the ‘problem’ of biology? Just use physics and maths, says Professor Robert Endres.

Words: Megan Welford / Photography: Hannah Maule-ffinch 

Professor Robert Endres is a man who searches for order in disorder. As a child, he liked all sciences, but says he was drawn to physics because of its clear-cut laws. “It’s the most fundamental science,” he says. “You can apply the laws to the universe and learn how the world works.”

Biology, he says, is messier, but no less fascinating. “I made a pond in our garden when I was 12 or so,” he says, “and I was amazed by the variety of organisms you could see in those one or two square metres, if you looked carefully.” But for the young Endres, looking wasn’t enough. He wanted to understand, and he’s still trying now.

“Physical laws can’t explain the emergence of biology,” he says. “Biology is really complicated. There are patterns, but they are often not reproducible in an experiment. Take the pond – insects and amphibians are complicated here. The pond is not a controlled environment – you have seasons, weather, water flowing in and out, frog migrations – so you can’t just study the frogs, you need to take into account the whole ecosystem.”

It’s that search for a pattern that has driven much of his work in biological physics. Despite initially enjoying the satisfying nature of the laws of physics, Endres couldn’t help being attracted to biology, finding at school that the most interesting elements of either living or non-living matter happened far from equilibrium. Emergent phenomena, like frogs, were interesting because they were more than the sum of their parts.

For his PhD, he studied small biochemical networks, their signalling pathways and how they turned on genes in response to their environment. And he became aware of a paper written by a visionary mathematician from the 20th century. “Alan Turing wrote one paper out of the blue where he said that biology, essentially, is a maths problem,” says Endres. The paper sets out a theory of ‘diffusion-driven instability’ to try and draw the patterns of biology using maths.

“It starts with a fixed domain on which molecules diffuse and start interacting, producing patterns. Turing is saying you can study two elements separately, but what happens when they interact is most interesting. Emergent phenomena again. At first, I didn’t think the paper was so interesting, althoughrofessor Murray Shanahan (BEng Computing 1984) was a the maths was beautiful. But now that I see the relevance to biology, I think it’s a wonderful paper.”

We’re trying to simplify biology and recreate its patterns in a robust way"

At Imperial, he began working with a professor of synthetic biology, Mark Isalan, who also saw the potential of the Turing Patterns. “The thing is, Turing just used chemicals,” says Endres. “You can make patterns with chemistry but it’s a bit boring. It’s very clean and easily controlled.”

On the other hand, biological phenomena such as embryos are “confusing and horribly complicated”. To try and avoid their myriad influencing factors, Isalan is instead building  questioning sort of child. “Aged around 10 or 11, I would lie awake at night wondering how we knew if anything really existed,” he remembers. “Was it down to information we received through our senses? I enjoyed these slightly alarming, we biology from scratch – engineering bacteria and observing how they grow and interact, trying to read the patterns. Endres brings the more detached eye of a physicist, looking at the bigger picture, trying to establish the parameters and the physical boundary conditions of the cells’ behaviour.

The pair are trying to understand what makes biology work. “What we’re trying to do is simplify biology to the point that we can understand and recreate its patterns in a robust way. If we understand what the patterns can do, then we can engineer cells to create tissue, and engineer tissue to create organs, for example. Until we can predict the patterns, it’s all a bit hit and miss. Someone might succeed in making a tiny clump of cells differentiate and get organised, for example, but they don’t know why it worked, and can’t do it again.”

Engineering organs is not Endres’ primary motivation, however. “There are many downstream applications,” he says, “but I would be happy just to understand the rules of biology in a physical world.”

Professor Robert Endres is Professor of Systems Biology in the Department of Life Sciences.