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Meet Peter Rugg-Gunn, researcher, policy contributor and engagement lead

Peter Rugg-Gunn is a Group Leader and Head of Public Engagement at the Institute, with a research interest in the epigenome during early human development. Peter is scientific lead of the Human Developmental Biology Initiative (HDBI), a member of the Scientific and Clinical Advances Advisory Committee of the Human Fertilisation and Embryology Authority (HFEA), and is active in UK and international efforts to establish guidance in stem cell-based embryo models. He is also an Editor for the journal , in which a version of this interview was first published.

When did you first become interested in science?

I liked lots of different things at school; science was one of them, but it wasn't a clear, standout favourite. In the UK, we have to narrow down our subject choices quite quickly and, faced with this decision, I moved towards science because it was the subject I enjoyed the most. After high school, I opted to take a very broad degree in Biology at the University of York to keep my options open. It wasn't until my final year that I started to take courses in developmental biology and genetics – at that point, I knew this was a core interest for me.

Was it at that point that you decided to pursue a PhD?

I wish it were that straightforward! After my undergraduate course, I didn't know what I wanted to do. Instead, I took a series of part-time jobs to fund my enjoyment of travelling. At some point, my supervisor from York, the embryologist Henry Leese, contacted me and said – in a very supportive, gentle way – that I had to decide what to do, and he was right; it was exactly what I needed to hear. Around this time, I attended a public lecture in Newcastle, where I was living, by Peter Andrews – a stem cell biologist. Peter was telling the audience about human embryonic stem cells, what they are, and what they might be able to do one day, and I remember being captivated by that topic. I mentioned this interest to Henry and he said that an American scientist, Roger Pederson, was relocating from California to Cambridge and that I should speak to him. This was around 2001, when President Bush put in place a ban on the use of federal funding for research using newly derived human embryonic stem cells and created quite a challenging climate to work on stem cells. I got on very well with Roger. I was excited about his vision to apply developmental and embryological principles to better understand human embryonic stem cells and how to coax them into the right specialised cell types. I thought that was tremendously exciting. I joined Roger's group initially as a research assistant and then switched to a PhD. So, it was a reasonably circuitous route, but one that involved a series of fortunate events and a lot of support that ultimately led me to my PhD.

What did you work on for your doctoral thesis?

My question was how epigenetically stable are human embryonic stem cells? There was a lot of excitement and hope that, one day, human embryonic stem cells could be used in cell replacement therapies – in addition to modelling development. But, as human embryonic stem cells are derived from embryos at a developmental period when they undergo epigenetic change, there were concerns that this plasticity could destabilise the epigenome. Reports at the time showed that some mouse embryonic stem cells could show epigenetic instability in certain conditions. One of the best readouts for epigenetic stability is that of imprinted genes (genes that have parental-specific expression patterns) because they're sensitive to epigenetic marks. I wanted to use allele-specific expression of imprinted genes as a proxy to understand whether human embryonic stem cells are epigenetically stable. Cambridge had many excellent groups working on genomic imprinting at the time and I benefited a lot, particularly from Anne Ferguson-Smith and her team. Human embryonic stem cells were new, and very few groups were working with them, so the first challenge was finding suitable conditions to grow different human embryonic stem cell lines. But the rest fell into place quite nicely once we'd realised how to do that. We found out that human embryonic stem cells possess a reasonable level of epigenetic stability, perhaps more than we were expecting, but there were some differences, including upon prolonged passage of the cells, when some instability started to appear (, ; ).

And after that?

As I came to the end of my PhD, I knew that I wanted to continue in research as a postdoc. I'd had the chance to meet Janet Rossant on a few occasions and, of course, was incredibly impressed with her and her science. I was absolutely delighted when she agreed to let me visit and speak to her and the team, and then invited me to join her lab in Toronto at the Hospital for Sick Children. The change was relatively smooth; Toronto is a very welcoming city. A few cultural adjustments were needed; I stopped drinking tea and switched to coffee – a habit I still have. Scientifically, the group was working at a very high standard and it was a supportive group; there were many opportunities to collaborate and develop ideas. It was very enjoyable, and those years were extremely informative. My wife and I enjoyed going to music concerts, and Toronto was a wonderful place for that too. It was a fantastic period in my life.

What projects did you work on while you were in Janet's lab?

One of the most exciting discoveries was the finding that, in embryonic stem cells, most regulatory sequences of developmental genes had a bivalent chromatin mark, meaning the coexistence of histone modifications that are typically associated with both active and repressive functions. These dual epigenetic markings were thought to hold developmental genes in a repressed state, while maintaining responsiveness to coordinated activation at the appropriate time. The key question for us was how generalisable this principle was: were bivalent chromatin modifications in pluripotent cells of the embryo? Did other types of embryo-derived stem cells also share these bivalent epigenetic features? The question with the embryo was the trickier of the two and required a period of very fine, painstaking microdissections to manually separate the lineages of very early-stage mouse embryos. It was quite tough to learn these fine skills at first, but then, once I got into the rhythm, it was quite relaxing and calm, spending hours sitting at the microscope. Coupled with obtaining these samples were newly developed methods that were capable of mapping histone modification profiles in small sample sizes. We were able to bring this technology to embryonic cells and found that, indeed, we could detect bivalent marking of chromatin for developmental genes in early epiblast cells of mouse embryos, which showed that this bivalent configuration was not only in embryonic stem cells, but also was a feature of undifferentiated cells in the early mouse embryo (). This finding has subsequently been extended by other groups using more modern methods. Furthermore, this finding holds true in other embryo-derived stem cell lines, which was technically an easier part of the project. We found that the strongest signatures by far were in embryonic stem cells, and the extra-embryonic stem cells had much weaker signatures of these bivalent modifications. It appears that those cells use alternative epigenetic markings to help regulate their developmental gene expression.

How was the process of becoming a group leader?

I interviewed at several institutes that I felt would be good environments to support my science, but the Babraham Institute near Cambridge had the strongest attraction. I was excited about the research being performed and the wonderful people and facilities that support the science. It's a friendly, collegiate institute and I was delighted when they offered to sponsor my fellowship applications. To cut a long story short, I secured a fellowship and returned to the UK to begin my lab at the end of 2011. The institute was a very supportive and welcoming place, and everyone was very patient with me as I found my way. Coming from Toronto to Babraham was much more of a culture shock! Babraham is a rather small village – it's very pretty, but it has only a few houses and one pub. At first, I enjoyed the short commute to work, but it wasn't long before we moved out of our short-term housing there and moved further towards the city.

Becoming a group leader was mostly thrilling and a little bit terrifying. We're well-trained in doing scientific research and you learn some aspects as you go, such as writing grants or interviewing. But, of course, there are other parts of the role that are just as – if not more – important. At the time, there was very little formal training for some of those other aspects; you might go from being a problem solver to a motivator to an arbitrator, and that's all in just one morning! You learn as you go, hoping that you usually get it right. Obviously, you sometimes get it wrong and learn from that experience. As a group leader, you set the tone. Your behaviour, language and decisions are very important and, ultimately, it's about how we want to do science. Here, we aim to be an outward and open-looking team and to enjoy our research.

What are your lab's current research interests?

Our current themes involve studying how the epigenome is first established in human development and how this impacts embryo development (reviewed by ). Although many of the key principles for epigenetic regulation are shared between species, there are differences in humans related to developmental timing, the factors that are expressed in the specification of lineages and the prolonged period of cellular plasticity before commitment. In my group, we use a combination of human stem cells, embryo models and embryos, to understand the molecular pathways that control the initiation of epigenetic processes. The primary system that we study is histone modifications, particularly Polycomb-group Repressive Complexes that are involved in both the memory of cell fate decisions made and in shaping future decisions. One interesting feature is that the histone modifications catalysed by Polycomb proteins undergo widespread erasure following fertilisation, which removes the gamete-inherited marks. Embryonic genome activation leads to the establishment of a new epigenetic programme to support embryonic development, which forms the foundation for the epigenetic information held for the rest of our lives. We're interested in understanding in molecular detail how Polycomb proteins gain their first foothold in the genome at these early stages. What are the strategies used by the cells to build on these initial events? Do these events endow lineage plasticity over this period? What are the consequences of errors in these processes?

Since your postdoc in Canada, you’ve maintained an involvement in informing policy. Why do you think it is important for researchers to do this and what have you learnt from it?

I believe scientists have a good opportunity to provide expertise to inform and hopefully improve decision making. And if we don’t provide the information then there’s the risk of a narrower view, potentially jeopardising a fair and balanced outcome. Science policy covers a very broad range of topics, from how research should be funded, organised and conducted, to how specific areas of research are regulated. So I think it’s about finding an area that you are interested in and then exploring how you can get involved. My experience is that helping to inform policy is rewarding, but the process in government of creating policies is extremely difficult and complex with many factors involved (scientific evidence being one of them). You may not always agree with the outcome, but if the process has been fair and everyone has had the chance to be heard, then that feels acceptable.

What is the HDBI and how did you become involved?

The is a Wellcome-funded consortium involving about 24 different research groups in the UK and Europe, all coming together to bring their expertise to support research on human development. The aims are to enable and support wider research on human developmental biology, to help build this community and to make it easier for researchers with different expertise to enter this field. My role as the scientific lead is to support the consortium, connect the teams, try to remove any barriers to their progress and look for ways to facilitate their work. As part of this, we've helped to develop imaging and transcriptomic technology hubs that researchers can access. These hubs are partnered with the (HDBR), which is a human embryonic and fetal tissue biobank. In parallel, there are collaborative scientific programmes to study how cell lineages are formed during human embryo development. For this, the consortium looks at various systems including heart and lung development, neural development, blood and immune development, and early embryogenesis. There's a lot of sharing of expertise and technologies and, importantly, close integration of public engagement and ethics built into the science programmes.

I was approached to take the scientific lead for the HDBI when the previous lead relocated overseas shortly after the HDBI launched. I was initially quite daunted by this responsibility, but I was impressed by the enthusiasm and engagement of the people involved. I liked their community-building focus and I happily agreed to take on this role about four or five years ago – I've been enjoying it hugely ever since.

You're also heavily involved in public engagement and dialogue. How did that come about and why do you think it's important?

Science is exciting, and it's essential to communicate that to different audiences and involve society in scientific decisions. It's important that the public understand what scientists are working on and why are they doing it, and we must remember that most of our research is supported by public money. There was a great deal of interest from the public on human embryonic stem cells (and more recently on human embryos and embryo models), but there is misinformation too – so it's important for scientists to be clear and open about their research. Being involved with these public engagement projects takes us out of our comfort zone, but I've always found them worthwhile and valuable. If we provide the right training, support and opportunities, then we create the right environment for more scientists to become involved.

In 2020, I was invited to become the Head of Public Engagement at the Babraham Institute. I've certainly enjoyed this position; developing and taking part in public engagement projects, thinking about the audiences we want to reach and the strategies we want to use. For example, when I started working with the public engagement manager at the time, we decided to engage much more with audiences and communities that were typically underserved by science and scientific opportunities. In the four years since we've begun to change this focus, we've seen about a five- or sixfold increase in the proportion of individuals we as an institute engage with from these underserved communities and we have put in place several new initiatives. We keep these connections with people we've engaged with to learn if and how these experiences have changed their views or decisions. It's very rewarding.

One question all this activity raises is: how do you manage it all? And how do you manage to achieve a work-life balance that works for you?

The main thing is that I work with fantastic people who are all excellent at what they do! I wouldn’t be able to explore my interests in the same way without them. I tend to plan my time quite carefully and try to be organised. The flip side of this is that I find it difficult to cope with last minute or unexpected requests, and this is something that I need to improve at. In terms of work-life balance, I enjoy my work, which is essential. I am also fortunate to have a supportive partner. I used to find it difficult to switch off and particularly any setbacks at work would bother me, but now I move on more quickly and switch off more easily. Outside of work, I enjoy taking part in different sports, particularly squash.

And to finish on a surprising fact, tell us something more about your life outside science:

Over the years, I've been fortunate to go on many fun adventures, from high-altitude trekking in the Himalayas to camping on the banks of the Zambezi River. You need a good team and an adventurous spirit – not unlike science.

Acknowledgement:

This profile has been adapted from , first published in Development on 12 July 2024 and developed from an interview between Peter Rugg-Gunn and Alex Eve, Senior Editor at Development.