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From Latin to the lab

From Latin to the lab

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 鈥 and why Latin grammar could yet come in handy.

Despite being a biochemist Dr Philipp Voigt has always had a problem with biology. 鈥淚n 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,鈥 he says.

The same penchant for principles accounts for his early love of Latin. 鈥淚t 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鈥檛 really think about its rules too much,鈥 says Philipp.

鈥淏iology doesn鈥檛 exist outside the laws of physics and chemistry. It just uses so many things to make these amazing and complex systems.鈥

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

鈥淧eople often say that biology doesn鈥檛 work like this but it does. Biology doesn鈥檛 exist outside the laws of physics and chemistry. It just uses so many things to make these amazing and complex systems.鈥

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鈥檚 new home. 鈥淲ith my PhD I went into signalling, so I鈥檝e known about the Institute鈥檚 work since then,鈥 he says. 鈥淚 moved into epigenetics as a postdoc and as I want to make connections between the two, there can be no better place than here.鈥

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.

鈥淭hese histone-based systems work by bookmarking genes as 鈥榦n鈥 or 鈥榦ff鈥, supporting the whole process of controlling the gene expression pattern that鈥檚 active in the cell,鈥 says Philipp. 鈥淭his supporting function is very important because like bookmarks, they make it much easier to find the page 鈥 or gene 鈥 you鈥檙e looking for in a long book or strand of DNA.鈥

Not surprisingly, there is much we don鈥檛 yet understand. A key area for Philipp鈥檚 new group is the epigenetic regulation controlling gene expression during development, where he鈥檚 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.

鈥淲e 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,鈥 he explains.

鈥淚f we can find some first principles that describe all these systems, then we have a fighting chance of emerging back into the light.鈥

The question of why a gene is bookmarked both 鈥榦n鈥 and 鈥榦ff鈥 has puzzled researchers for years and theories that this serves to keep genes primed or poised for action are still controversial. 鈥淲e know both these bookmarks are there, and that these genes are then activated or repressed during development. What we don鈥檛 know is whether the same things would still happen if those bookmarks weren鈥檛 there,鈥 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. 鈥淢y dad turned87 this year, and when he went to school, DNA wasn鈥檛 even a thing! The same with the asteroid impact that wiped out the dinosaurs 鈥 that was a mystery until the 1980s. Knowledge has developed so fast over the past 50 years 鈥 but we鈥檙e still discovering new things.鈥

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. 鈥淲e are reaching a point where you can鈥檛 know everything you need to know in order to do what you鈥檙e trying to do,鈥 he concludes. 鈥淚f we can find some first principles that describe all these systems, then we have a fighting chance of emerging back into the light.鈥