An interview with Marysia Placzek

Congratulations on being awarded the Waddington Medal. What does this award mean to you?

Thank you, it is a real honour and means a lot to follow in the footsteps of previous awardees. I care passionately about developmental biology, especially developmental neurobiology, so it's an opportunity to talk about this amazing field. At the same time, the award lecture allowed me to introduce the talented researchers who have worked with me over the years to bring us to the understanding that we have today.

We're here at the Oxford hub of the EDBC meeting, where it was also announced that you're going to be the next president of the BSDB. Why did you decide to take that role on?

I'm less busy than I have been for the last 30 years, because all my children are now grown up. The BSDB is a wonderful society, with many valuable traditions, including its support of junior researchers. It has the ability to promote developmental biology more widely, and I think that there are real opportunities to pick up and run with that. Paul [Martin, current BSDB President] and his colleagues have started to do so through a series of videos and films and building on their work will be really important.

We heard your award lecture last night, where you took us through your career. Going back to the start, is there a moment that you can pinpoint when you first became interested in science?

There were two key moments. My Dad used to get the New Scientist and the Scientific American and, at the age of 16, I read an article that discussed cloning, plasmids and genes. These were alien words and concepts; this wasn't the biology we were taught at school. But I tried to understand and read around the subject, and that's when I decided to study molecular biology in Edinburgh, where Ken and Noreen Murray had developed one of the country's first undergraduate courses in this field. I then completed my PhD in London, and found that, sadly, molecular biology didn't appeal to me at the bench. And not only did it not appeal to me, but I was poor at it. Conceptually I thought it was exciting, but on a practical level I just didn't achieve very much. That's when I switched fields and went to Jane Dodd's lab at Columbia University, USA, working in collaboration with Tom Jessell. In the first week, I was invited to dissect a rat embryo. That was the moment that was absolutely transformative for me – I couldn't believe how amazing it was to see the progression of embryonic development. And that feeling has never gone. I've dissected so many embryos but, every time I see one, I'm overawed at this incredible transformation. It's extraordinary.

Do you still get into the lab?

I try to get into the lab about half a day a week, because I love looking at embryos, performing micro-dissections, the calmness needed to set up experiments and the excitement of what each new experiment might reveal. It certainly beats sitting in front of a computer.

Why did you decide to make the move to New York for your postdoctoral work?

Towards the end of my PhD, a postdoc in the lab introduced me to the ‘Spemann organiser’ experiment and so, in a lucky twist of fate, development and neurobiology were on my radar. My husband [Andy Furley] was especially keen to perform postdoctoral studies in the USA and experience a wider network of people, and Martin Raff helped me to identify up-and-coming developmental neurobiology labs in the USA. We interviewed in numerous labs, but were both offered positions in New York, so moved there.

During that postdoctoral period, you made some discoveries that significantly contribute to our current understanding of neural development. Could you talk us through those?

The significant finding is that embryonic midline groups act as local organisers. In the developing spinal cord, midline notochord and floor plate cells pattern the dorsal-ventral axis of the neural tube, and subsequently midline floor plate cells direct the growth of axons. These basic findings provided an explanation for how the spinal cord develops in such a coherent manner over time.

You mentioned in your award lecture that you were working with Marc Tessier-Lavigne at the time, and that it was a very collaborative project. Is that emphasis on collaboration something that you've carried forward in your career?

Yes, working with Marc was fantastic and, since then, I have maintained and encouraged the collaborative aspect of science. Marc was an extraordinary colleague. He and I used to sit down, side by side, dissect, and set up experiments together. And we chatted away all day long, talking about our work and about science more broadly, and we learned so much from each other. I also learned a lot about myself. When the time came to publish our first paper, I realised that I didn't particularly care about [first versus second] authorship position. I'd had such a ball. The work had been so much fun. It had been such a fantastic experience. Going forward, that's just how I've always worked. I enjoy working with other people and collaborating on the science, and I think two heads are better than one. You can talk to people and bounce ideas off each other as you're going along. You can challenge each other. And I think that leads to better science.

Following that work, you came back to the UK and took up your first independent position at the National Institute for Medical Research (NIMR) in London. What were you working on at that time, and how did you go about establishing your own research niche?

One of the last observations that I had made in Jane's lab was that a ventral midline group may extend into the developing forebrain, and pilot experiments suggested that it shared some (but not all) characteristics with posterior floor plate. So I decided to ask how forebrain floor plate-like cells form. Nobody was asking that question at the time. It was a very logical and simple step to take, following the embryo in a very natural way. I found that forebrain floor plate-like cells are induced by the underlying prechordal mesoderm. So establishing my own research niche didn't demand much, other than careful observation of the embryo. The embryo will point to the questions that are unanswered and that need to be addressed.

You then moved to the University of Sheffield. What influenced that decision?

There were three factors. First, I was brought up in the Lake District and love to walk in hills and swim in cold rivers, which is difficult around London. Second, I enjoy teaching. There were some possibilities to teach at the NIMR, but teaching was not integrated into daily life. Third, living in a London commuter town was challenging. We had two young children by now, and we were always the first to drop the children at the nursery, but the last to get to work, and the first to leave work, but the last to get to the nursery. As much as I loved work, I loved the children even more, and wanted to have more time with them. At the time, Phil [Ingham] was recruiting developmental biologists to Sheffield. Sheffield is only 2 h from London, and is a super place to live. It has hills and rivers. We found a house 10 minutes from work in one direction and 10 minutes from the Peak District in the other direction. And with the group of people who Phil was attracting, and his vision to put Developmental Biology on the map at the University of Sheffield, it was an exciting opportunity. So it was a very simple decision to make the move.

You're now co-editor with Cheryll Tickle of the Principles of Development textbook. Was the decision to get involved in that project influenced by your interest in teaching?

It certainly was, because I think students still value a book, and they value being able to follow lectures if they're based on the logic of a book, so I was honoured to get involved. Initially I was asked to rewrite the chapter on neural development, which hadn't been touched for a little while, and then asked to step in a little more broadly. So yes, it was influenced by the fact that I like to help students to understand this quite difficult subject.

Can you summarise the main research themes of your group at the moment?

The main research focus of the lab is to understand the development of the hypothalamus in the ventral forebrain. The hypothalamus mediates homeostasis. It is crucial for the survival of the individual and the survival of the species, yet very few labs in the world focus on hypothalamic development. Arguably, amongst the different regions of the brain, we understand its development the least. The reason for this is that the developing hypothalamus is relatively tiny, morphologically complex and develops deep down in the brain in a region that is difficult to access and visualise. For these reasons, we use the chick as a model organism, where the developing hypothalamus is relatively large in comparison to mouse and zebrafish. A main finding from our research is that the hypothalamus develops through a mechanism in which growth and patterning are intrinsically linked, that the ventral forebrain in sculpted in a very different manner to the dorsal forebrain and that hypothalamus development is closely linked to eye development. This work will have wide implications for our understanding of how particular cell types in the hypothalamus develop, where they originate and who their neighbours are at any particular point in time in development.

How have new technologies such as single-cell sequencing influenced your approach over the years?

I was lucky enough to be introduced to single-cell sequencing by Seth Blackshaw (PI at Johns Hopkins), and we initiated a collaboration that has massively accelerated my own understanding of hypothalamic development. It is as if I have been working on a jigsaw puzzle for 30 years and suddenly can fill in so many pieces. The amount of data and resources that come through single-cell RNA-sequencing analysis is absolutely astonishing, especially when combined with pseudotime analyses. To give one very simple example, many people over the years have been interested in the differentiation of particular types of hypothalamic neuronal classes. Beautiful studies in zebrafish and mouse revealed that progenitor cells expressing Islet 1 give rise to POMC neurons that regulate feeding behaviours. That work took years; it was painstaking, it was laborious. Now (through our collaboration with Seth and his colleague, Thomas Kim) at the click of a button, we can see a trajectory from an early progenitor state, through an intermediary second and then third state, to a point that progenitors express Islet 1 and then mature to POMC neurons. We can identify novel genes that are likely to play a role in POMC neuronal development. When coupled with new techniques that enable multiplex analyses, such as RNAscope and hybridization chain reaction in situ, we can look at how the patterns of genes change over time, relative to one another, in a way that was not possible before.

What do you think are the most exciting questions in your field at the moment?

In the field of hypothalamic development, I think it will be important to explore how the hypothalamus is integrated with other local tissues. The hypothalamus mediates homeostasis because it is situated in such close proximity to, and forms an interface with, other regions of the body including the pituitary gland and the foregut. I think that the most exciting question is how those tissues are collectively assembled in time and space in the developing embryo so that they function appropriately.

In Sheffield, you were the director of the Medical Research Council (MRC) Centre for Developmental and Biomedical Genetics, which became the Bateson Centre during your tenure. How did you find the experience of leading an institute?

I fell into the directorship fortuitously. Phil [Ingham] established the MRC Centre, and one of its key roles was to attract clinician scientists and make them aware of powerful disease models, especially the zebrafish. Phil then left to take a sabbatical in Singapore for a year, but that year was then extended, so I took over – first as co-director, and then director. That meant truly finding out what my colleagues were interested in, and then promoting them and their science. So, to some extent, I set aside my own ambitions to promote my junior colleagues, mentoring them to reach their potential. That was both a challenge and a pleasure. One of the things that brought us together as a group was the ability to showcase the research in the Centre through EMBO Workshops, Royal Society summer exhibitions and centenary events. The zebrafish is a very powerful tool that captures the public's imagination.

Inevitably, MRC centres have a finite amount of time, and so I then led its transition into the Bateson Centre. In order to do that, and to drive the research forwards, I led the development of a screening facility to analyse zebrafish behaviour. That was quite separate to anything that I was doing in my own lab, which largely focused on the chick, so I found myself writing grants to promote a resource that was essential for colleagues. But it was good to do, because it brought the community together. Science is quite hard, so having some sense of community, and having a sense that somebody cares about you, and about your science, is important.

Picking up on that, it sounds like the hypothalamus community is quite small. Is that sometimes a bit difficult?

I've always chosen to work on questions and topics that interest me, and that I am curious about. I'm delighted if other people are equally fascinated, but it doesn't make me depressed if a piece of work has a smaller-than-anticipated impact. But it's harder for PhD students and postdocs, who benefit from being able to discuss their work with others and may want other people to engage in what they're doing. This is why I think working as teams is so important, and why our collaboration with Seth Blackshaw and Thomas Kim was – and continues to be – so tremendous. We initiated the collaboration just before lockdown, and it helped to keep momentum even when the labs were shut. We still hold regular online meetings, and these help my lab to appreciate that their work is of wide interest. With Seth and a number of other colleagues, we're constantly trying to promote our small community. I hope that, in the near future, many more labs will be attracted to study the hypothalamus as it becomes easier to understand its development.

It sounds like you take mentoring seriously. I was wondering if you yourself have had any significant mentors who have influenced your own approach to mentorship?

I certainly have, I've had lots of people look out for me. Marc Tessier-Lavigne helped me to prepare my first ever conference talk, and Tom Jessell and Jane Dodd coached me on preparing my first job interview. Phil was also very supportive over the years, and I know that at various points in time Cheryll Tickle and Liz Robertson stepped in to support me behind the scenes. But even 20 years ago we didn't really have mentorship in the same way as occurs now, and to some extent I muddled through. My own approach to mentorship has been to make time for individuals and let them know that I care. In my case, I was heading my own lab and directing the MRC Centre at the same time as raising four young children. I used the same approaches – listening, sharing, caring – whether dealing with my children, my lab or my wider colleagues. It just seemed the natural thing to do.

Finally, what do you consider to be your greatest contribution to your field?

That's a really hard question! I think the biggest contribution will be a new understanding of how the forebrain is built.

Marysia Placzek was interviewed by Laura Hankins, Reviews Editor of Development. This piece has been edited and condensed with approval from the interviewee.