Pathway to Independence – an interview with Polina Kameneva

Let's start at the beginning, when did you first become interested in science?

It began in high school when I started to have more in-depth biology classes. My teacher saw my interest in biology and ecology, and she advised me to prepare for the Ecology Olympiad. In Russia, this is a very typical thing to do: you go through the school competition, then on to the city level, regional level and, finally, national level. I went through all of the steps, and I really enjoyed it. I knew then that wanted to enter some scientific field, whether it was ecology, biology or biochemistry. When it was time to choose, I chose to major in Biochemistry because of Professor E. Kostetskiy in the School of Natural Sciences of the Far Eastern Federal University. He is extremely enthusiastic and charismatic, and he has his own theory of life's origin on Earth. That was very intriguing and exciting, and I thought to myself: ‘I need to study here.’

Where did you do your PhD, and what were you working on at that time?

I did my PhD in the Far Eastern Branch of the Russian Academy of Science, in Vladivostok, Russia. I knew that the Far Eastern Federal University had a very close connection to the Academy of Science. One of the greatest features of the programme was the practical courses organised by scientists at the Academy of Science Institutes, including the National Scientific Centre of Marine Biology. Through their enthusiasm, I got exposed to real research questions. For example, in our region, people would go and collect shellfish such as clams and mussels during summer to have them for picnics. However, they didn't know that there are toxic microalgae that live in the same waters, and the shellfish can be poisoned. That was a big health concern, and one of the labs in the Centre of Marine Biology had a microalgae monitoring programme. They needed someone with expertise in biochemistry to analyse toxin accumulation patterns. I thought that it could be a great chance for me to apply my expertise to this project. I was very motivated by the idea of doing something for human health and helping my region. I did my PhD in the field of marine biology studying microalgae and toxin accumulation. We actually showed, for the first time, that one of the microalgae species was toxic. I remember the feeling that I knew something that no one else knew and I was about to share it. That was a very special moment that just got me really hooked on science.

Did you enjoy the interdisciplinary nature of that project, at the interface between biochemistry and ecology?

To be honest, it was not easy; it was a constant search for compromises and a common language. I will give you one example of choosing the committee for a PhD defence. In Russia, you have set, specialised committees; for example, one committee will only cover developmental biology, and another committee will only do ecology. I presented my thesis to different committees, but they were not sure that all parts of the thesis could be equally discussed. In the end, I defended in the ecology committee with invited biochemists. It was very exciting to discuss the results with people from different fields and perspectives. I remember this experience as very enriching and motivating.

How did you decide what to work on for your postdoctoral studies?

I wanted to join my husband in Stockholm, Sweden, where he was doing his postdoc, and I was looking for some projects in marine biology. Luckily, we crossed paths with Igor Adameyko. He is famous for discovering the role of nerves and associated Schwann cell precursors for peripheral nervous system and neural crest lineage development, among other things. On top of this, he is a marine biology enthusiast. I was hoping that he would help me to orient myself in marine biology research in Sweden. We were discussing different projects and he had an idea about studying the development of myelin – a lipid-based sheath of the nerves. From my PhD project, due to the lipophilic nature of marine toxins, I had experience in characterising lipids by mass spectrometry. Igor thought we could maybe apply these skills to a project on myelin in the lamprey and other basal organisms and he suggested joining his lab and trying it out. Unfortunately, the lamprey project didn't really take off, but I joined the lab and started to learn about the fascinating process of development. At first, I was helping the other postdoc, and now my great friend, Maria Eleni Kastriti, with her project on the development of chromaffin cell organs, and through this I became intrigued by adrenal glands. I didn't really plan to transition to a different field, but I am happy I kept my eyes open to new opportunities. I did something new, challenged myself and I think it became very fruitful.

Did you find this transition to working with quite a different model organism challenging?

Yes, it was absolutely challenging, and I was transitioning to a completely new field. I was basically going back to the bachelor level and reading a lot of literature to figure out how things like transcriptional factors work. I think it requires a lot of courage, especially in the moments when you feel like you don't understand many things. So, one needs to know how to cope with imposter syndrome when changing fields so radically.

And conversely, do you feel it's benefited you, having that challenge in your career where you've had to adapt?

Yes, definitely. Once you have these challenges, and you just have to push yourself, then you realise that you are so capable and that you can learn so many things. This gives a big boost of confidence. I'm so inspired by the students that we have in the lab now, who are curious and ask questions. I believe that the best way to learn something new is to talk to experts and ask as many questions as possible.

How did you hear about Development's Pathway to Independence Programme and why did you decide to apply?

I think it was through Twitter. I immediately thought that the programme would really help me because I actually felt quite lost. I am really enjoying my postdoc position as Igor encourages his team members to be independent thinkers and we have intellectual freedom. But I knew that I needed to transition to being a PI to advance my career. Then I realised that I did not get trained to be a PI at all, and there was a whole new set of skills that one needs to master. As a postdoc, you get to design experiments, read papers effectively, gather information and analyse your results, but you don't learn how to manage and motivate a group of people, and how to handle the administrative side of things. You might not even know how to approach collaborators. So, it's really tough to transition from a postdoc to an independent position. That's why I instantly decided to apply to the Pathway to Independence Programme.

What do you hope to get out of the programme?

I'm already getting a lot. It was really nice talking to my mentor, Liz Robertson, and getting her support with the interview that I had at one of the research centres here in Vienna. She helped with my application and gave me a lot of encouragement before the interview. I am looking forward to the mentoring sessions when we will talk a little bit about what to expect and how to deal with the challenges of being a PI. I also think that the exposure we will get is a really nice feature of this programme; I often think that maybe I should do more outreach and talk about my projects and my plans, but sometimes it's hard to find time and an opportunity for this.

Where are you in the process of securing an independent position and what has your experience been so far?

I am considering several opportunities. One is securing my first funding, which can be through the European Research Council Starting Grant, or through the FWF Foundation (Austrian Science Fund). At the same time, I plan to apply for positions here in Vienna, to those places that give some starting funds to young PIs, such as the St. Anna Children's Cancer Research Institute. My husband is also a researcher here in Vienna, so we decided that we would try our chances in Austria first. Vienna is an amazing place for research; there are many research institutes with innovative, advanced, state-of-the-art facilities and great traditions. A lot of Nobel laureates conducted their research in Austria. The pharmacological industry also supports the research here. This all contributes to a really nice research environment. If this plan does not work, we will try to find positions elsewhere, but we would prefer to stay here.

What excites you most about becoming an independent researcher?

I was thinking the most about this question because, in Igor's group, we are already quite independent. All of us are running our individual projects, and I have some students who work with me. Transitioning to independence would mean less research at the bench for me, and more administrative work. I hope I can manage it, without sacrificing so much research time. I imagine when I build my team of motivated people to work on my own idea, it will become something special and transformative. It is quite unique to see the evolution of ideas and progress that you work towards together with like-minded people. I am looking forward to synergies of ideas, fun discussions and cracking some challenges.

What do you think will be the most challenging aspect of being a PI and how will you prepare for it?

I think the most challenging part is securing funds. From what I see, more than 50% of a PI's time is spent designing ideas, applying for grants, securing collaborations and participating in different consortia so you can get further funding. I am not used to applying for grants yet. When I drafted my first application, it took me a long time and it was really hard. But it gets easier – I think it's like a muscle that you train: the more you apply, the better it becomes. I try to prepare myself for accepting that many of these applications may not be successful. I wish there were more widespread schemes of non-competitive universal funding to reduce the risk of job loss for academics. I think it is very stressful to realise that, if you are not successful at securing further funds, the positions may no longer exist.

What research questions would you like to address with your own group?

Some types of cancers get primed during embryonic development. For humans, these stages of development are not easily accessible. Now the situation is changing – we live in a time when researchers can create organoids and synthetic embryos, which pretty closely mimic the development of some tissues in a dish. Together with this, new technologies are allowing us to discover new features of normal development and of disease on a single-cell level. For example, by matching single-cell transcriptome profiles of tumours and healthy tissues it was possible to pinpoint the exact cell lineages involved in tumour emergence. Unfortunately, what we still don't know is how the onco-transformation process is initiated. But we know that some cells can resist genetic perturbations associated with cancer, meaning that these changes do not result in tumours. What are the mechanisms behind initiation and resistance? Does plasticity of the differentiation process play a role? Can we control it? I want to try to generate models where we can induce these genetic perturbations and then follow the development of the human cells in organoids. We can compare lineages with or without these mutations and try to find those initial events which turn a cell to the dark side.

How did you decide on this research niche for your future lab?

This is the combination of two of my postdoctoral projects. During the first part of my postdoc, we were building an atlas of human adrenal gland development, and I was studying different aspects of how the cell populations control the size of the adrenal gland medulla during development. I learned about different tumours which can appear in adrenal glands, including paediatric neuroblastoma and the adult-onset tumour pheochromocytoma. I met the Gustavsson family, who founded the Paradifference Foundation to support research of paraganglioma and pheochromocytoma. Not only do they support projects, but they also regularly bring scientists together for a conference to discuss their progress and exchange ideas. My integration into this network of people who are deeply interested in adrenal gland development and pathology led me to some open questions, but I was lacking the tools to address them. When I moved to Vienna, I started to work with human stem cells to develop stem cell models for neural crest differentiation. I submerged myself in learning about the new technological approaches and possibilities they provide, and the direction for my own work got clearer as I learned to use the necessary tools. I discussed these opportunities with Igor, because it was also important to check which projects could be started in his lab to generate the preliminary data that I would need to apply to funding programmes. It was a very honest conversation; he's very supportive in this direction.

What are the key questions that you think your field will be looking to address in the future?

We now have the atlases of gene expression and epigenetic profiles, and even more modalities (such as proteomes, phospho-proteomes and metabolomes) will be included in future. We need to find how all this information integrates at the cellular level. Cells are able to live in a noisy environment but still take good decisions about what they need to become and what they need to do. We don't fully understand how cells are so good at this, and what breaks in the case of disease. I think researchers will try to unpick this. I think that using machine learning algorithms that can analyse a lot of factors at the same time will help reveal some connections. Hopefully, those connections can be validated in the relevant biological system. The other direction is to improve the synthetic models, which replicate different tissue types in a dish, and then use them to probe for predicted mechanisms and carry out drug screenings. It takes a lot of time to move findings to the clinic, and then into actual use. I think organoids could help to speed up this process.

How valuable do you think mentorship is in navigating an academic career?

I think this is the most important factor. I think that choosing a research group based on the people who work there is the way to go. Many things excite me in science, but I think having a community in the lab, where people support each other, is of utmost importance. I think mentorship has been the key to 80 or 90 percent of my success. My supervisors and mentors, Igor Adameyko, Peter Kharchenko, Gennady Kamenev, Tatiana Orlova, Andrew Imbs, helped me to grow as a scientist and as a person in academia. Sharing their views and values, they inspired me along the way, and I hope that I can be as inspiring for the next generation.

Has collaboration been an important aspect of your career so far?

Incredibly important. If we look at the author lists of recent papers, we can see that they are often the collaborative efforts of many groups. For our project on the role of serotonin in adrenal gland development, I think we collaborated with 28 scientists from 17 research institutes. Everyone contributed with experiments across several research models, fruitful discussions, analysis of data and shaping of the manuscript. At first, I could not believe we would integrate all the results; we had data from different animal models, pharmacological and behavioural experiments and neuroblastoma cell lines, but also some field samples of wild animals collected in the forests of Siberia! In the end, it worked, and I am so proud of that project, because everything supports the main claims. Now, when I am applying for new funding for my own research, I am reaching out to some of the collaborators, and they are so kind to share the material and to provide support. It is really encouraging to realise that you are not alone, that there is this whole network! It feels great and gives a sense of community and security.

Finally, what do you like doing outside the lab?

My other passion apart from science is cooking, especially anything that involves working with dough: baking waffles, making bread, pasta, dumplings, anything. It makes me really happy when I can invite my friends and we cook and enjoy something good together.

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