Maria Almuedo-Castillo is a Junior Group Leader at the Andalusian Center for Development Biology (CABD). Maria's group studies how mechanical forces are translated into the gene regulatory signals that impact a cell. We spoke to Maria over Teams to learn more about her early-career research, her transition into being a group leader, and her insights into navigating the academic profession.
Let's start at the beginning, when did you first become interested in science?
When I was a kid, cancer research was a relatively new hot topic that was often televised in mainstream media. I was blown away after seeing photos and videos of a research lab for the first time. As an unrealistic child, I remember dreaming of curing cancer when I grew up. In the Sunday newspapers that my father bought, I was drawn to the sections featuring scientific discoveries. Eventually, when it came to choosing a career, I wanted to study biology, or more specifically, molecular biology, because molecules are the key to understanding how a living system works and what could have failed in a disease condition.
I gather that you pursued a PhD at the University of Barcelona, working on Wnt signalling in planarians. What attracted you to this topic and what were the main findings of your PhD work?
After completing my undergraduate degree in Biology at the University of Seville, I moved to Barcelona to pursue a Masters in Developmental Biology and Molecular Genetics. There, I became fascinated by both the city and my dissertation topic, which was focussed on planarian flatworms as models for regeneration. If you cut one planarian into, say, 20 random parts, each of these would regenerate into a whole new worm! One aspect of planarian regeneration that particularly interested me was how the pre-existing tissues re-adjust/re-scale to fit into the smaller size of the new animal, which is only a part of the original animal. I decided to continue working on this model for my PhD. A part of my project showed that a non-canonical Wingless/Integrated (Wnt) signalling pathway regulates neural connectivity during nervous system regeneration, while also playing a role in the apical positioning of the cilia in planarians (Almuedo-Castillo et al., 2011; reviewed by Almuedo-Castillo et al., 2012). The other part of my PhD work involved trying to understand the re-scaling event that occurs during planarian regeneration. I found that the stress-activated c-jun-NH2-kinase (JNK) pathway induces apoptosis in wounded cells, which is essential for coordinating tissue-renewal, remodelling and the maintenance of a correctly proportioned animal in planaria (Almuedo-Castillo et al., 2014). The topic of tissue remodelling and re-scaling remained one of my core interests during my postdoc as well.
You then moved both experimental system (from planaria to zebrafish) and country (from Spain to Germany) for your postdoc. What was the motivation for this move and how was your postdoc experience?
I changed my experimental model because, although the planarian system is amazing, it has its own limitations. During my PhD, I was interested in conducting some imaging analyses in vivo; however, planarian eggs are laid within cocoons, which makes it extremely difficult to obtain clear images of the animals during their initial life stages. Also, at the time, we did not have any established framework for carrying out mutagenesis or transgenesis experiments in the planaria field. So, I chose the zebrafish model because it is perfect for visualisation and quantitative imaging, and the field routinely uses excellent genetic tools. However, the move from PhD to postdoc was quite challenging, as expected. During my PhD, I was in a very collaborative environment, where the supervisors were always accessible, and I received a lot of support from my peers, whereas in my postdoc lab at Max Planck Institute of Tübingen (Germany) the dynamics were quite different. Everybody was involved in their independent project, and I needed to learn everything by myself. Also, there were other challenges associated with moving countries as well; I was not fluent in German, so there was a language barrier. Overall, it was a challenging but enriching experience. I got acquainted with several nice people, and I learnt a lot about the zebrafish model and in vivo quantitative imaging. We also managed to get some nice experimental results. So, at the end of the day, the good things will stay with me.
What was the main summary of your postdoctoral research?
During my postdoc, I investigated how the proportions of all the germ layers are re-scaled in a newly formed zebrafish embryo. Working alongside a colleague in the lab, who was a mathematician, we developed a model based on the Nodal-Lefty signalling pathway that regulates germ layer patterning. Our computational analysis predicted that the inhibitor, Lefty, which is highly diffusive, increases in concentration in smaller embryos, thereby inhibiting Nodal activity. Our in vivo studies confirmed that the ability of Lefty to diffuse throughout the embryo and its high concentration levels are essential for embryos to scale their tissue proportions. Together, our work revealed that the inhibitor, Lefty, regulates size-dependent inhibition of Nodal signalling, which allows normal patterning in zebrafish embryos (Almuedo-Castillo et al., 2018).
When looking for group leader positions, what was particularly important for your search, and why did you choose to start your lab at the Andalusian Center for Development Biology (CABD)?
I moved from Germany to CABD to do a second postdoc before settling into my current role, which gave me a preview into the institute beforehand. CABD is very focussed on fundamental developmental biology, which agrees with my personal philosophy. As an institute, we support basic and fundamental research, while also trying to highlight how our work can be applied for greater benefit. Also, CABD fosters a very collaborative environment within an intimate space, making this institute a nice place to work.
I also had to consider some personal limitations when choosing to start my own lab. At the time, I had already had one of my kids and I was pregnant with my second. Considering the obligations I had to my family, my hometown (Seville) seemed to be the most viable option. I was lucky that CABD is in Seville, which made it easy for me to start my research group here.
So far, what has been the best moment and what has been the most challenging moment in this transition to being a group leader?
I think every part of this process is challenging. The transition itself was a significant hurdle. I became a mother around the same time as I was trying to step into a group leader role. This step in the academic career demands a lot of energy, motivation and time. So, it was difficult to navigate all these needs with the demands of a newborn. Beyond this personal perspective, I think as a new group leader you have to deal with all sorts of administrative tasks along with running your own experiments, because initially you do not have the money to hire research students or a lab manager. On top of that, you need to continuously prove your worth as a PI in the institute in terms of space, leadership and independence because of your junior position.
The best moments are when I come out of my office now and see some of my newly appointed research students chatting with each other and sharing a laugh. It makes me feel like my lab has a healthy environment. Also, when you first devise the hypotheses and experimental plans as a group leader, you are not sure whether any of that will work. So, when the students and researchers in your lab get their first positive results, it is a moment of big relief.
The best moments are when I come out of my office now and see some of my newly appointed research students chatting with each other and sharing a laugh
Do you have any insights that you would like to share with early-career researchers who are looking to start their own lab?
Well, it is very important to be innovative while deciding on the research topic for your group. I would also suggest being realistic with your expectations and to ‘dream big, but not too big’. Although it is necessary to draw the big picture for grant applications, I think it is important to design realistic projects for your first cohort of students based on your preliminary results. Having backup plans also helps to tackle the frustration of failed hypotheses for your students and yourself. Being reasonable and transparent with your long-term plans will also help you achieve the key objectives within the first few years (depending on your institute), which might be required for a promotion to a full-time PI position. Furthermore, it is important to chat with your colleagues and fellow PIs to know more about individual experiences and how your institute functions.
Can you summarise the current research themes of your group?
We are interested in mechano-sensation: how the coordination of multiple inputs, such as tissue mechanics, cellular geometry and gene regulatory networks define the gene profile of a cell and impact the global cellular epigenome. We track early developmental stages under different biological contexts in zebrafish and in organoids. This also enables us to analyse whether an organoid resembles the native organ in terms of epigenetic and mechanical properties.
How did you navigate the field to find your niche?
I was always interested in quantitative imaging techniques, early developmental stages, biomechanics and biochemical signalling. When choosing your niche as a group leader, you have to find the right balance so that you can use knowledge from past experiences but also be innovative and independent. So, I tried to develop a project that was outside of the scope of my previous supervisors, while keeping in touch with my own strengths and interests. At the start, I did not plan on having such an ‘epigenetic and genomic’ lifestyle, but it is one the strengths in my current institute and it also helped in progressing the current projects in my lab.
In your group, what has been your approach for hiring new team members?
The first level of screening comes from reading their CVs to check whether their experience fits within the scope of the lab. During the subsequent interview processes, I usually try to have a genuine conversation with them. I look for candidates who demonstrate their enthusiasm and open-mindedness. Also, it is important that they are nice human beings and can fit well with the members of my current group. Of course, some of the selection criteria vary depending on whether you are hiring for a PhD student or a postdoc. When hiring for a postdoc position, I tend to look for someone who is driven and can independently manage projects, whereas for PhD positions I look for enthusiasm and eagerness to learn.
How important do you think mentorship is in navigating an academic career?
Mentorship is everything! The academic journey is difficult both professionally and personally. So, it is crucial and invaluable to have a mentor who you can trust and rely upon. It is quite a struggle when you do not have the right person to support and guide you through the failures.
In your opinion, what are the exciting areas in your field?
Currently, the field of mechanobiology itself is extremely interesting. Studies that investigate the impact of mechanical forces in cell morphology and migration, or how an organ/embryo is shaped in a specific way due to underlying mechanical properties, are simply fascinating. I am also in love with studies that utilise high-resolution imaging to capture how certain transcription factors enter the cell nucleus when the nuclear port opens as a response to mechanical pressure.
You were on the Scientific Organising Committee for the 18th Spanish Society for Developmental Biology Meeting that was held in October. How did you get involved in this, and how has the experience been?
I am not exactly sure how I was nominated for this role. During my postdoc, I got in touch with a group of female scientists who currently run the Spanish Society of Developmental Biology. So, I was probably already in their radar, but I am unsure of the exact reasons. It was a very nice and smooth experience. As a part of the Scientific Organising Committee this year, I had to read all the submitted abstracts and shortlist the most interesting ones. However, in 2026, I will be on the Event Organising Committee for the SEDB, which will be a totally different experience.
Did you ever consider an alternative/non-academic career path? What and why?
To be honest, I have thought about changing my career path several times in the last few years, especially after my postdoc. I even considered going to university to study medicine so that I could find a more stable job that is more recognised in the society. However, I did not do that. In my current role, I am happy most of the time because, as scientists, we love what we do every day. For instance, when a simple PCR or an imaging experiment is successful in the lab, or when I am talking to my students and teaching them something, I feel happy. As long as I can forget the endless administrative parts of the job, it is an exhausting but enjoyable profession.
In my current role, I am happy most of the time because, as scientists, we love what we do every day
Finally, is there anything Development readers would be surprised to learn about you and what do you like to do in your free time?
I do not usually have a lot of free time outside of work because I am raising my kids and also taking care of my dad. Occasionally, when I do get some time to myself, I love running. You would be surprised to know that before I started my PhD I was also in the Spanish rowing team!
Maria Almuedo-Castillo's contact details: Centro Andaluz de Biología del Desarrollo (CABD), 41013 Seville, Spain.
E-mail: [email protected]
Maria Almuedo-Castillo was interviewed by Saanjbati Adhikari, Features Editor at The Company of Biologists. This piece has been edited and condensed with approval from the interviewee.