From Latin to the lab

Dr Philipp Voigt joined the Institute in December 2021 to set up a new group in the Epigenetics programme. But on leaving school he wanted to teach maths and Latin. Here, he explains the biological conundrums he aims to answer – and why Latin grammar could yet come in handy.

Despite being a biochemist Dr Philipp Voigt has always had a problem with biology. “In school I never liked biology; there were too many facts to memorise that were seemingly unconnected. But I did like physics and chemistry. There, you have a set of rules or principles that you apply to everything in order to explain the facts,” he says.

The same penchant for principles accounts for his early love of Latin. “It was the first foreign language I had in school, and so the first time I really got to understand grammar. When you acquire your native tongue, you don’t really think about its rules too much,” says Philipp.

Today, what once frustrated him about biology now fascinates him. A system of rules must exist, it’s just that biological systems are so mindbogglingly complex that the rules are very hard to discover, he argues.

“People often say that biology doesn’t work like this but it does. Biology doesn’t exist outside the laws of physics and chemistry. It just uses so many things to make these amazing and complex systems.”

The area he wants to help bring order and understanding to is epigenetics, although he began his research in signalling. Both are fields where the Institute is a world leader, so Philipp is delighted to have the Institute as the team’s new home. “With my PhD I went into signalling, so I’ve known about the Institute’s work since then,” he says. “I moved into epigenetics as a postdoc and as I want to make connections between the two, there can be no better place than here.”

An overarching focus for epigenetics is the fact that the same genome in every cell in our body gives rise to many different cell types. The key question, therefore, is how does one set of instructions produce such dizzying diversity?

There are many ways we think this happens, including transcription factors and histone proteins, which work together to orchestrate the process.

“These histone-based systems work by bookmarking genes as ‘on’ or ‘off’, supporting the whole process of controlling the gene expression pattern that’s active in the cell,” says Philipp. “This supporting function is very important because like bookmarks, they make it much easier to find the page – or gene – you’re looking for in a long book or strand of DNA.”

Not surprisingly, there is much we don’t yet understand. A key area for Philipp’s new group is the epigenetic regulation controlling gene expression during development, where he’s focusing on modifications to histone proteins. As well as being responsible for keeping DNA tightly packed into cells, these proteins also have a regulatory job to do.

“We want to understand how the presence of one bookmark influences the presence and function of another. We are working on one particular set of combinations of two bookmarks, each of which has a different modification, one of which is thought to be active and the other repressive,” he explains.

The question of why a gene is bookmarked both ‘on’ and ‘off’ has puzzled researchers for years and theories that this serves to keep genes primed or poised for action are still controversial. “We know both these bookmarks are there, and that these genes are then activated or repressed during development. What we don’t know is whether the same things would still happen if those bookmarks weren’t there,” says Philipp.

Knowing more about these systems is important, because as well as turning genes on and off correctly during development, when these systems begin to fail during ageing they cause disease. Based on epigenetics, researchers in allied disciplines are already using epigenetic targets to develop new ways of treating cancer, and understanding how genes are regulated in early development might also provide important insights that enable us to make specific tissues for regenerative medicine.

Despite the huge challenges ahead, Philipp often draws on the history of science for inspiration. “My dad turned87 this year, and when he went to school, DNA wasn’t even a thing! The same with the asteroid impact that wiped out the dinosaurs – that was a mystery until the 1980s. Knowledge has developed so fast over the past 50 years – but we’re still discovering new things.”

As science delves ever deeper, each new discovery seemingly throws up additional questions, and this ever expanding body of knowledge brings him back to Latin and the grammar of language. “We are reaching a point where you can’t know everything you need to know in order to do what you’re trying to do,” he concludes. “If we can find some first principles that describe all these systems, then we have a fighting chance of emerging back into the light.”