Transitions in development – an interview with Berna Sozen

Can you take me back to that first moment you became interested in science?

Figuring out exactly when I got into science is tricky – it was more like trying to make sense of things and connecting with the science world. No one in my family was a scientist; my brother and I are first-generation college graduates. My understanding of what science was and why diving into it was a good idea was kind of hazy. It meant putting in some extra effort and self-directed exploration. I think the turning point came when my older brother decided to go to medical school, and I remember I was very inspired by the idea of digging deep into how the human body works. This made me interested in biology, and that interest led me to obtain my undergraduate degree in biology. During my time as an undergraduate, it was the embryology course that truly captivated me; I thought how a single cell becomes an entire organism was an exciting process and I decided to learn more about this topic. At that time, very little was known about the early stages of human development, but I wanted to know about humans and that's why I explored an initial career in in vitro fertilisation (IVF) and ultimately decided to pursue postgraduate research in developmental biology.

You received your Master's degree in Reproductive Biology from Akdeniz University School of Medicine, Turkey. Can you tell me about your research project during that time?

I enrolled in a Master's programme in Reproductive Biology to primarily study embryonic development. But, once I got in, things took a turn – I ended up getting involved in a bunch of research projects covering everything from gamete biology to the physiology of reproductive organs. The approach was all about translating research into practical solutions, with a big focus on infertility studies. Because IVF is a major part of treating infertility, our studies were heavily influenced by what we learned from IVF clinics. I was also very motivated by the idea that my studies might help individuals and families dealing with fertility challenges. I was also an intern in the IVF clinic for short time, and later obtained clinical embryology training.

However, since the first moment I saw a human early embryo developing in the IVF clinic, I have been captivated by the question of how this tiny ball of cells could eventually become a human being. I think it was the privilege and the excitement of ‘seeing the unseen’. I became more and more interested in basic developmental biology and I wanted to start using mouse embryos for experiments. However, this topic wasn't a strength back in my home institute in Turkey; my late supervisor, Dr Necdet Demir, was a neuroscientist and there was no infrastructure in the entire department about how to culture and manipulate mouse embryos. So, I had to establish embryology tools through reading literature (I've learned a lot through protocols published by experts such as Janet Rossant). In resource-scarce environments such as Turkey, we had to get creative. For example, I was collecting leftover culture media from IVF clinics to use for my research projects. Despite all the limitations, I am grateful for becoming engaged with the reproductive biology community at the start of my scientific journey. It taught me a ton and showed me how to ‘connect the dots’ in these interrelated areas.

You also spent some time during your Master's at the University of Southampton, UK. How did that come about and what did you work on while you were there?

Although I had an intense passion for developmental biology, performing cutting-edge research in this field was challenging at my home institute. I started looking for opportunities to learn from established experts and world leaders in the field. I knew the work of Tom Fleming, who was a pioneer in understanding the cell biological mechanisms of early mouse embryo development. He was like a legend to me. I applied for a short-term scholarship, which enabled me to gain research experience in Tom's lab at the University of Southampton. I soaked up a ton of knowledge about experimental embryology during my time there – it was one of the turning points in my training.

In Tom's lab, I worked on understanding how the maternal environment can impact embryonic development. I was using maternal diet models to investigate how alterations to the immediate metabolic surroundings influence the molecular pathways directing embryonic development during the peri-conception window. Early embryos demonstrate remarkable adaptive plasticity, but these adaptations incur long-term costs on adult health. Learning this concept of plasticity and the concept of ‘developmental programming’ was exciting for me and it has become a major interest of my research in my lab.

What was it like for you to move from Turkey to live and work in the UK?

It was very stimulating, both on the personal and academic level. Cambridge, especially, was an exceptional place to do research. There's such a strong developmental biology community, with everything you could ever need right at your fingertips. In a place like that, it's all about what you can imagine.

Life-wise, I didn't feel any major culture shock. I adapted to the UK pretty quickly, even though English as a secondary language was a challenge for me at the beginning. I guess for most science immigrants coming from a poor socio-economic background, there's this drive to hustle extra hard to catch up. I was spending pretty much all my time in the lab, but it didn't bother me – it was a joy.

You stayed enrolled at Akdeniz University School of Medicine for your PhD alongside working with Magdalena Zernicka-Goetz at the University of Cambridge, UK. What attracted you to that lab?

Having spent time in Tom's lab in Southampton during my Master's, I quickly recognised the disparities between my Turkish institute and the global scientific landscape. I really wanted to apply to PhD programmes in the UK but, at the time, this did not seem possible, mostly because of financial constraints to covering a PhD programme in the UK. So, I decided to pursue a PhD in Turkey. My thesis proposal was within what I could propose in Turkey: to investigate key signalling pathways, such as BMP (bone morphogenetic protein) signalling, during pre-to-post-implantation development using cultured mouse embryos. Meanwhile, I also explored options to obtain a research fellowship as a visiting student in the UK, which led me to join Magda's lab in Cambridge during the second year of my PhD. Magda's lab has a long history of studying early mammalian embryos, which I thought was a great match for my interests. With the studies progressing productively, my stay was extended in Cambridge, where I conducted the longer term research for my PhD studies. It's been a journey of pushing boundaries and turning possibilities into realities.

What did you work on during your PhD?

During my time in Cambridge, I teamed up with an amazing PhD student, Sarah Harrison, to produce embryo-like structures from embryonic and trophoblast stem cells (Harrison et al., 2017), which marked another big shift in my scientific journey. After spending years digging into embryos, I began translating all that in vivo knowledge into developing in vitro models of embryos using stem cells. Cambridge was a very stimulating environment – I truly loved every minute I spent in there.

You stayed in the Zernicka-Goetz lab for your postdoc, first in Cambridge and then moving to Caltech, USA. What did you discover during this period?

Science-wise, I had a very rewarding time in the Zernicka-Goetz lab and worked with some great colleagues there developing several different stem cell-based embryo model platforms where each study built upon one another, and each project refined the next. Specifically, our focus was to reconstruct all the cell types, including extra-embryonic cell types, in the developing embryo. Our first mouse model, where I worked with Sarah, was a discovery in the sense that not only embryonic stem cells but also their extra-embryonic companions (trophoblast stem cells) were able to self-organise and they do so jointly to form structures that resemble post-implantation mouse embryos (Harrison et al., 2017). Later, we showed that extra-embryonic endoderm stem cells could also join this self-organisation feast and this led to the generation of ‘ETX-embryos’ (Sozen et al., 2018). Each model system deepened our understanding of embryonic/extra-embryonic lineage crosstalk.

How was the transition of moving from the UK to California, USA?

Rough! I moved to Los Angeles in summer of 2019, having never been to the west coast of the USA, which I regret a lot. The move came with a culture shock, which was unexpected and something I never really felt when I moved to the UK. It took me some time to adapt to California: using different words, the time difference, and the distance from my family and friends. From the first day, I knew that I would not stay in California for the long term. Caltech, on the other hand, was a great opportunity to interact and work with brilliant scientists from very diverse backgrounds. Caltech is more technology driven, which was different from my experience of the developmental biology community in Cambridge.

When did you start to look for independent positions?

When I relocated to the USA, I was in my tenth year of postgraduate training, which included a Master's, a PhD and a postdoc. At that point, I was very sure that I was ready to apply for independent positions. I had multiple first-author papers from my training. Also, being involved in a lab move provided me with a lot of valuable insights about setting up a new research space. I began exploring available positions and entered the job market with the mindset that, even if things didn't work out, I could always reapply the following year.

What did you prioritise during your job search?

So many factors become important when you are in the job market. For me, the primary focus was finding a place where I could genuinely be independent and well supported. Institutional support was the number one priority to me. I was also more interested in searching for positions in large universities where I could see myself becoming involved in interdisciplinary studies and collaborating with diverse expertise from my immediate environment. I believe interdisciplinary research fosters innovative thinking, creativity and the consideration of multiple angles when addressing complex problems. This is exactly what you need when approaching a scientific question. Hence, collegiality came as another priority when searching for a position. Yale has a very supportive environment and interdisciplinary science. Being an early career researcher is challenging; funding is very competitive, employment is insecure, and gaining experience in the skills needed to form a successful lab can be difficult. Leadership in the Yale Genetics Department understands this and provides exceptional support and vision for early career researchers.

How did it feel to start your own lab?

Starting your own lab is an exciting but also very challenging endeavour. I felt a huge responsibility to nurture and support the scientific careers of those under my mentorship. Transitioning from a postdoc, where the primary focus centres on personal achievements, to a group leader meant that it cannot be just about ‘you’. There are several different ongoing projects that you always need to keep up with and guide each trainee to ensure optimal outcomes for everyone. The nature of this role is relentless and brings countless challenges. Nevertheless, I feel lucky to say that there have been many good moments in a relatively short amount of time! For example, the first day I taught my trainees how to dissect mouse embryos, the first successful experiment and preprinting this work recently (Cao et al., 2023 preprint) was very moving. Receiving the acceptance for our first publication in the summer of 2023 (Pedroza et al., 2023) was another precious moment. Celebrating the recent fellowships awarded to two of my PhD students added further joy and fulfilment to this rewarding journey. I think to ensure maximum productivity, fostering a positive lab culture and mutual respect, and cultivating collaborations are key in a lab.

Do you think mentorship is important in navigating an academic career?

Mentorship is key in academia. I acknowledge that mentorship comes in different styles, but there's nothing worse than an abusive group leader who does not offer mentorship and support in your academic growth and career. During my scientific journey, I've constantly learned new and different things from each of my mentors, which prepared me to be independent and I am grateful for this. My current department fosters a faculty mentorship programme, which offers guidance in early career stages. I became a group leader after not spending much time in the USA, and certainly did not know a lot of things about USA-based funding, academic structure, etc. My faculty mentors, Valentina Greco and Andrew Xiao, have been very helpful and supportive to me since the beginning of my independence.

What has been your approach to hiring?

This was very important to me. Thankfully, I had a lot of interest in my lab from various cohorts, and several of them contacted me through Twitter/X. Once meeting with the candidate, the decision is determined by what they want to study and whether I am the most suitable mentor to guide them on their journey. It is really important to make sure it will be a good fit mutually.

How has your background and experience shaped your scientific philosophy?

Everybody has their own history, and I am very passionate about helping people from low socio-economic backgrounds have access to research and academia. For example, I think about how I can make sure I can give some salary support or help with the visa situation, which can be hugely expensive. Now, I'm very glad people are discussing diversity and inclusion, but I feel that socio-economic status is still not being discussed enough and there are barriers, especially in the USA, to what support you can provide. I'm trying to actively seek support for such people. Supporting individuals in these circumstances is crucial; when provided with assistance, these students have the potential to achieve remarkable accomplishments.

You've received several accolades since starting your group, including the NIH Director's New Innovator Award. What do these prizes represent to you?

They hold profound significance and motivation for me. Getting recognised with these prestigious honours is like getting a boost of support and resources that help my team keep pushing the limits of what we can discover in science. Moreover, they serve as a testament to the collective efforts and contributions of everyone in the lab, emphasising the importance of collaborative and forward-thinking research. It's not just about me; it's about all of us.

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

The main research theme in my lab is to define regulatory mechanisms that underlie developmental progression during mammalian embryogenesis. We ask how mammalian embryo develops, how it interacts with maternal neighbours, and how intrinsic metabolic mechanisms influence embryonic decisions. To tackle these questions, we use mouse and human embryos, along with stem cell-based models derived from them. These diverse stem cell-based embryo model systems have been serving as valuable tools to interrogate questions that were highly challenging before, especially in human development (Pedroza et al., 2023). Although these model systems provide valuable insights, there is still much ground to cover as they bring forth their unique set of questions.

Additionally, developmental metabolism is a central interest for me. For a long time, metabolism has been seen as permissive to development, but we now know that it directly instructs development through interactions with key genetic and signalling factors. We try to understand how this guides cell identity and behaviour in embryonic development (Cao et al., 2023 preprint). In addition to identifying how essential metabolites are utilised to coordinate embryonic differentiation, we are also exploring the connection between maternal environmental triggers and embryonic dysfunction, such as the impact of excesses of specific metabolites within the intrauterine metabolic environment on the early embryo.

Your research is at the forefront of young and emerging fields, including human stem cell-based models and developmental metabolism. Are there any associated challenges?

Since the very first day I started working on developing these stem cell-based embryo platforms in 2015, when the field was just emerging, I was sure they would be game changers. It was so exciting to be a part of these developments in Cambridge and it's been amazing to see how the field has progressed so rapidly in a relatively short space of time. However, this area of research remains drastically underfunded in the USA, with federal sources still not funding work on native human embryos or complex embryo-like structures. Funding is much needed to propel creative research programmes and overcome these significant barriers in the field.

In your opinion, what are the exciting areas in your field right now?

I think there are a lot of exciting areas happening with new emerging technologies – I am not sure where to start! Understanding many enigmas surrounding human embryo development is becoming more and more feasible everyday with new tools being developed, and this area of research is fascinating. Another example is modelling the maternal environment through the use of bioengineering platforms that combine sophisticated organoids and stem cell-based embryo models will allow researchers to interrogate dynamic cellular processes.

Finally, what do you like to do outside of the lab?

I've been very interested in photography – mostly landscapes and architectural design – for many years. These days I struggle to find time outside of the lab for photography (or for anything really!) because I have a baby and I like spending my time with my family.

Berna Sozen was interviewed by Alex Eve, Senior Editor at Development. This piece has been edited and condensed with approval from the interviewee.