For the first instalment of the In Conversation With… series, I sat down with Reinhard Stöger, who runs a laboratory at the University of Nottingham, UK and is a member of the Epigenetics Society Board.

Really good to speak with you! Firstly, can you tell me a little bit about your background?

Yeah, of course. I studied biology in Vienna, and at that time, there wasn’t any molecular biology on offer at the university; that’s how long ago it was. I then pursued a master’s, which turned out to be quite a chaotic episode.

But then I got really lucky, because the IMP in Vienna opened. This is the Institute for Molecular Pathology, founded by Max Birnstiel, a big shot who was the first person to purify a gene using ultracentrifugation. I went to Denise Barlow’s lab; she was a young investigator and didn’t have anyone working with her yet, and I asked if I could do a PhD under her supervision.

Denise really knew her mouse genetics. She was isolating genes using what was then a state-of-the-art approach: “chromosome walking”; this is something that is obsolete now that whole-genome sequence information is so readily available. When I started, Denise gave me a big list of papers, and she put me in the library at the IMP and said, “Yeah, you’re gonna read.” I think she made me read just papers for almost a month — no lab work — and then said, “What do you want to do?”. And I chose to work on something called genomic imprinting.

What was your work building on?

It was actually work by Mary Lyon that interested me; she was a brilliant geneticist, and in 1964, had narrowed down a genomic region on mouse chromosome 17 that seemed pretty funky: Johnson then reported 10 years later that if you had chunk of that chromosome deleted (Hairpin-tail deletion) and it was inherited from the father, there was no effect, so you had normal offspring. However, if the same deletion came from the mother, the embryos would die in development: an epigenetic phenomenon!

My PhD was basically finding that gene in this region of mouse chromosome 17 at a time before any genome had been sequenced. After a lot of blood, sweat, and tears, I found a CpG island that mapped within that deletion. It turned out to be the promoter of the insulin-like growth factor 2 receptor (Igf2r).

There was another group working on identifying the first genomically imprinted gene, and in terms of publication, we beat them by about 2 or 3 months That was, I think, in January 1991. It was a big race at that time to find it. Their group then showed that the insulin-like growth factor 2 is also imprinted, but in the opposite way. I was a bit spoiled by the experience. It was hard work, but my first ever publication was a Nature paper and the second a Cell paper. I thought, well, maybe this is how science works. It was a crazy start to a scientific career.

I was also very interested in memory and brain function, and how this works at the molecular level. A talk by Charles Laird really sparked my interest in working on Fragile X syndrome, a common genetic disorder that causes developmental, behavioural and learning challenges. I got an Austrian Erwin Schrödinger fellowship, and this allowed me to move to Seattle to work with Charles at the Fred Hutchinson’s Cancer Research Centre. And of course, this was Seattle at the height of the grunge scene — Nirvana and all that, so an exciting time to be there…

And you’re now working in Nottingham, UK, so you’ve had quite an international career. And what are you working on now?

I have a small lab. Amongst other things, we started working with honeybees some time ago, because they are a classic example of environmental epigenetic programming: nutrition in early life influences adult phenotype. There is one protein in royal jelly that has been claimed to confer the “queen” phenotype in bees, called royalactin or Mrjp1. It’s not set in stone, but we have some evidence that this protein helps to maintain pluripotency, at least in mouse embryonic stem cells. This plays into something I call “alien epigenetics” — how foreign components influence the host epigenome.

Along these lines, we also found that honeybees are sometimes infected by bacteria, which have a lot of a specific type of DNA methylation called 6mA. When we sequence the infected honeybees’ genomes, we find there are certain genomic regions with surprisingly high levels of 6mA, a modification that is normally considered to be present only at very low levels in animal DNA. What does it all mean? We’re working on it!

I imagine honeybees must be quite a hard organism to study. What do you think the biggest challenges are?

There are ethical and biosafety issues if you want to experimentally infect honeybees. In theory, you can keep them contained, but in practice it’s quite difficult. Bumblebees, which are more distantly related, are much easier to maintain and can also be infected with this type of bacterium. You can essentially buy them off the shelf, and they’re much easier to manipulate and study experimentally in the lab.

Where do you think the most exciting developments are being made in the field right now?

I think an exciting area is understanding how different organisms interact with and potentially manipulate each other at the epigenetic level. This is largely missing from the field because we tend to study the epigenome of an organism in isolation, unless there’s an obvious pathogen involved. Understanding how organisms manipulate each other’s epigenomes might also give us new tools for manipulating the epigenome ourselves. We already know that epigenetic manipulation can influence ageing in cells. You can turn back the clock a little bit, and I think if we can learn to do that in a controlled manner, that’s exciting.

What advice do you have for younger people thinking of starting a science-related career?

Try to communicate science, because by doing so, you educate yourself. It’s a good training for writing grants or collecting your thoughts and communicating them to others.

The other thing is to work on what you’re really interested in and find a supervisor that you feel comfortable with. Some people just aim for a big-name lab but in terms of satisfaction it’s good to get along with the supervisor and be happy with the topic.

What do you do outside of work to enjoy yourself and relax?

I draw! My cousin is a painter, and I was quite attracted to that more Bohemian, artistic lifestyle, so I wondered whether that might be more fun. So I gave painting a go for about half a year, and then I figured out, actually, I do like science a lot. I now go once or twice a week to life drawing sessions. It’s very nice to activate some other parts in the brain in addition to just reading about science. Otherwise, I go to the gym and cycle back and forth to work, and the usual stuff: music and reading.

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