Transitions in development – an interview with Margarete Diaz Cuadros

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

I have been interested in science, specifically biology, since I was a child. My mother also had an interest in biology, which she instilled in me. When I was young, instead of reading me bedtime stories, my mom would read from the encyclopaedia or books about animals or plants. My mother was not a scientist, but she probably would have made the best scientist if she had had those opportunities.

At what point did you move from Peru to the States?

When I finished high school at 17, I moved to New York for college at Columbia University. I was young and bold, but I feel like today I would not be that brave! I still struggled a bit with the transition and connecting with my peers. Probably what shocked me the most was a level of wealth and privilege that I had never encountered before. In my sophomore year, I joined Martin Chalfie's lab, where I found my home away from home. The lab was, and continues to be, really diverse with people from all over the world. I felt there was more room to be different in the lab than there was with my undergraduate group – it was where I started to get that feeling of belonging in the USA. It was in Marty's lab that I understood what an academic research career entailed – and I loved it! I love the notion of dedicating your life to studying research questions that you find interesting. I was very inspired by Marty, who is such a huge advocate for fundamental research, and he instilled this in me 100%.

Why did you decide to join Olivier Pourquié's lab for your PhD and what did you work on?

I did three rotations as part of the Harvard Biological and Biomedical Sciences PhD program, and my third was in Olivier's lab. I can actually recall the specific moment when I knew this was the lab for me: when I saw a movie of a mouse embryo with a fluorescent reporter for the segmentation clock. It was beautiful. I already felt at home and supported in Olivier's lab, and then there was this ‘click’ with the science – it was what I wanted to study. I wanted to understand why the segmentation clock has a different period in different species. For example, the period is 90 min in chicken, but 2.5 h in mouse. We knew about this specificity, but we didn't understand the molecular basis for it – and we still don't! We decided to develop stem cell-based models of the segmentation clock where one could have stem cells of different species because we thought this was the best system for the question. It was honestly a huge change for me; I had expected to work on embryos. After we generated and described mouse and human stem cell-based models of the segmentation clock, we used them to try to assess the role of metabolism in those species differences (Diaz Cuadros et al., 2020, 2023).

You were successful in obtaining several grants and fellowships during your PhD. What advice would you give to graduate students looking for similar opportunities?

It is good to have your own funding; it can give you a certain degree of independence and autonomy in the lab, and it greatly enhances your CV, although it doesn't give you a bigger salary. It can also open networking and community-building opportunities through the fellows in the cohort; I had a Ford Foundation fellowship (part of the National Academies of Sciences, Engineering, and Medicine), for scientists from under-represented communities, which fostered the network of Ford Fellows through an active distribution list. It has been really rewarding, even if I don't post often, to hear what the other fellows are up to.

Quantity is important: go for anything that you are eligible for to maximise your chances and get advice, input and examples from people who have received those fellowships in the past. I was privileged in that Harvard has many resources in place to help their students apply for fellowships, such as dedicated staff, seminars and workshops. I was also very lucky because I am a US citizen, and eligible for many opportunities. International students have a severely limited selection of fellowships that they can apply for. We should be advocating for more opportunities for these scientists who come to our countries and gift us their talent.

You went straight from a PhD into an independent position. Is that common and how did you achieve this?

I am part of an independent fellows program, of which there are a few in the USA. I think the most commonly known are the Whitehead Institute Fellows and the Sandler Fellows at the University of California, San Francisco. Essentially, an independent fellow program is an alternative to the traditional postdoc period where you start your own small group. Usually, these positions are temporary and last for a period of five to six years to begin developing your research program, after which you still have to apply for assistant professor positions. Independent fellowships are a huge opportunity, but also a huge risk. One could end up failing completely because one needed that additional training and mentorship from the postdoc. My personal motivation for pursuing an independent fellowship, even though I could use more training, was that I had completely fallen in love with the research question I was studying and I wanted to work on it for the rest of my life. The field of developmental timing was also coalescing, and I didn't want to miss out on those foundational years. I was fortunate that Cliff Tabin, who was on my thesis committee and is the Chair of Genetics at Harvard Med, had himself been a fellow when his career started. I ended up taking the same position that he had, an independent fellow at MGH. I was lucky to have that connection to someone who had gone through the same experience and who was able to connect me with a position.

Was it a daunting task to start a lab so early in your career?

Yeah, it was hard. Every person I spoke with who had been a fellow before warned me not to do it and said it was the hardest time of their life. I didn't believe them – I thought it was going to be different for me. In fact, it has been as challenging as they said it would be, but it's also been just as rewarding – a crazy roller coaster. My motivation going in was the science. I wanted to work on this specific research question, but when I started working in the lab and when I started having trainees, I realised that science and scientific questions are only half the picture. I found that it was as, if not more, rewarding to build a mentorship relationship with the people in my lab and to see them grow and help them advance in their careers. I'm in a position where I have the scientific motivation that I originally had but have found a second motivation, which is mentorship. Mentorship is at the heart of academic science; our most important purpose is not the discoveries we're going to make but the fact that we're training the next generation of scientists to be the next academics, as well as professionals in biotech, industry and regulatory roles in government.

Who have been your own mentors?

I would never have been able to get to where I am today without my mentors. Marty showed me what it means to be a scientist and that it's okay to be passionate about basic science even when there's such a strong push for translational research. What I gained the most from Olivier is optimism. He always had a positive outlook and this calmness that is the opposite of me – I'm the first person to panic, to catastrophize whatever is happening. Olivier was also very generous as a mentor, and at every opportunity was advocating for me. In my new department at MGH, the junior faculty have been extremely supportive in terms of mentorship. It's key to have not only mentors who are more advanced in their careers but also mentors who are at your same level and have been where you were a month ago and have solutions. My more senior mentors in the department, Gary Ruvkun, Margie Oettinger and Vamsi Mootha, have also been huge role models and basically reinvigorated my enthusiasm for science and showed me different kinds of lab leadership styles. I learn from them every day.

Can you summarise the research themes of your group at the moment and how you found that niche?

In the last few years, there's been a renaissance in studying developmental timing. There are many great groups working on this now. In terms of carving out our own niche in this emergent field of developmental timing, part of it is that we took the angle of looking at what can be the potential role of metabolism in setting up developmental speed. We have several projects looking at metabolism and mitochondrial biology in the context of developmental timing, but I also felt that something limiting the field was that all the work was hypothesis based and there was no room for high-throughput, unbiased approaches. One of my goals was to introduce unbiased approaches to the field of developmental timing, which we are doing in a few ways. One approach is genome-wide screens in human cells, which is still in the early stages. Another approach is to introduce a new model in the lab, Caenorhabditis elegans, for which there are many resources for doing unbiased genetics. We can look at an entire organism across its lifespan and, crucially, we can do screens. We are doing old-school EMS mutagenesis screens to try to isolate worms that develop faster than normal. We're also doing some quantitative genetics where we look at different wild isolates of C. elegans, some of which just naturally have slight differences in developmental timing; they either grow faster or slower than the standard laboratory strain. We can use those differences to find real genetic variation in the wild that drives differences in developmental rate through either QTL or GWAS mapping.

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

Many cellular processes have now been described to regulate developmental timing, from the work we did on metabolism, to biochemical reaction speeds, protein stability, and epigenetics. What is still missing, however, is being able to pinpoint genetic causes. How can we find genetic variants that drive the difference in developmental speed between species, as opposed to general descriptions of the molecular biology that gives rise to differences in timing? There has been some work towards that, for example, from Alexander Aulehla's lab with Ali Seleit using QTL mapping with different species of medaka fish (Seleit et al., 2024). I am really thrilled to see that as the start of finding the genetic variation that underlies different developmental timing. It will be really exciting in the next few years to see the field engage with and discover these genetic variants.

What has been your approach to hiring new team members?

As scientists, we're not trained for this part of the PI job. I took part in the EMBO Lab Leadership course, which was helpful. Some of the concepts that we implement in the lab come from that course. I also took a course from the NIH called Raising Resilient Scientists aimed at faculty mentors. There were a lot of concepts in there from psychology or behavioural science that were completely new to me and that I'm trying to engage with and discuss in the lab. There are two things that are important to me when hiring. First, hire people who have skills that complement your own. You're not just looking for little copies of yourself, but for someone who can bring something new to the lab. For example, I was going to become a new PI, and I knew I am very messy and disorganised, which is not a good trait to start a lab! The first person that I hired, Katie, is someone who has such amazing skills for organisation and she has set us up with systems that are going to be sustainable long term. Our second hire, Jack, has a level of attention to detail that I simply cannot achieve. It also can be scientific skills. The first postdoc that I hired, Gabriel, is very good at biochemistry, and I cannot do biochemistry at all! The other thing, which is just as important, is that I want to hire people who share my vision and values. My first job ad didn't say, ‘seeking highly motivated applicants’, it said, ‘I'm looking for a kind, curious soul,’ because those were the values that I was looking for in a person; someone who is kind and empathetic and can help us build a positive lab culture, and who is curious about the science and willing to engage with it at all levels. I was very deliberate about building the lab culture. We have all heard horror stories about toxic labs, and it was important to me that I not allow that to happen under any circumstance in my lab. To build that culture, in addition to making sure we have the right people in the team, we worked on defining our lab values and the ways in which we want to embody them. Our lab values are humility, connectedness and curiosity. There are other ways to bond, not necessarily values, and build that lab culture. One needs to diversify the strategies to make sure that there is something that works for everyone, but it won't be one size fits all.

Could you tell me about your involvement in science activities in Peru?

When I was a PhD student, I was a co-director (one of three) for the Research Experience for Peruvian Undergraduates (REPU) program (www.repuprogram.org), which aims to provide internship opportunities to undergraduate students who have shown great promise and talent, but do not have access to lab training opportunities and experiences that will give them the boost they need to reach the next stage in their careers. We conduct an open search and then match up a cohort of about 20 selected applicants with labs in the USA or Europe. What is unique about this program is that we take an approach that is highly based on the importance of representation. We don't send the students just anywhere, only to institutions where we have a volunteer mentor who is themselves Peruvian. Importantly, they do not go to this mentor's lab, but another (highly supportive) lab in the same institution. REPU is entirely volunteer based without institutional funding. It's run by people who want to contribute, which is highly inspiring and allowed me to find a community of other Peruvian scientists.

I have also been involved with the Committee for the Advancement of Women in Science in Peru, which was directly linked with the government via CONCYTEC, the National Council for Science, Technology and Innovation. Each year, they appoint a committee to make recommendations to the council on how to promote the advancement of women in science. I was appointed to this committee for only one year because they rotate pretty frequently, but I try to continue contributing in any way that I can. It was rewarding to engage directly with my home country, but, at the same time, it was a little frustrating because some of the concepts or strategies that I would implement in the USA cannot be applied in Peru because of a lack of resources, such as the students you're trying to reach might not have internet access – things as simple as that.

What other equity, diversity and inclusion initiatives do you participate in?

I am highly invested in building the community in the Department of Molecular Biology here at MGH. I want to make sure that the department is as welcoming as possible to everyone and that everyone in the community has a sense of belonging. My desire to do this kind of work comes from personal experience and from the work with REPU. As a Latina from a developing country, there have been many instances where people have disregarded me because of who I am, and I saw students from REPU face similar challenges. When I became a PI, I wanted to help turn my department into a place where people like me wouldn't struggle by building on the work done by the Diversity, Equity and Inclusion Committee. We have many initiatives, such as affinity spaces that bring together different groups of people with minoritised identities. We also work to improve mentorship, such as to make sure that postbac students have all the resources needed to persist in science, and to support postdocs.

You've said you always wanted to be a biologist, but was there any point you considered a non-academic career?

I've never seriously considered another career path – they're going to have to kick me out of here; I'm not going to go willingly! But that doesn't mean I don't have days when I find my job frustrating and that I don't fantasise about being a baker. I think we all fantasize about the road not taken, but, truthfully speaking, there's nothing else I would rather do.

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

I love to be at home with my husband, Jose, and our dog, Moshi, either watching a movie or playing fetch in the yard. I also really enjoy cooking; specifically, I try to continue cooking Peruvian food. Whenever I go back home, I return with a suitcase full of ingredients to cook. It drives my husband crazy, but then he enjoys the food, so he can't complain! During the summer months, I spend a lot of time out on my vegetable garden, and we recently got chickens, so I also spend time with my hens.

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