We always begin at the start of the academic journey. Did your scientific interests emerge organically? Was there a moment, or someone, who inspired and ignited your passion for these fields of knowledge?
I come from a non-academic family. I was the first in my extended family to earn a university degree, so it certainly wasn’t through family influence that things happened. That said, family influence was important in sparking my curiosity, and for that I owe a great deal to the close relationship I had with my paternal grandfather. He only completed primary school, as was common in those days, but he was a deeply inventive person who had a kind of workshop at home and was always creating things. That was probably the most influential factor in my pre-academic environment. Things unfolded quite naturally after that, as I progressed through school. I was always curious. I didn’t spend much time studying, but I absorbed things with great eagerness. Everything felt new, like opening an encyclopedia and being able to step inside. Back in my day, the ninth year of school was experimental, you could choose a vocational area and then either stick with it or switch. My aptitude tests pointed equally to science and the arts, so I first decided to try arts. It was interesting because I had a bit of talent for drawing, also inherited from my grandfather, but the course was in art and design, and it turned out to be far more design than art! My design teacher was a fashion designer, so I ended up spending a year sketching clothes, which I hated. But I’m grateful to that teacher, because she showed me a path, and that it wasn’t the one for me. At the time, I had a close-knit group of friends, and we shared many years of intense experiences together. Most of them were going into science and technology, and that appealed to me too. Since I’d already tried arts and disliked it, I decided to give science a go. In truth, I really enjoyed chemistry and biology, and I was lucky to have an extraordinary biology teacher, one of those people who leave no one indifferent. Professor Elisa Bacelo, whom I hold in great esteem, truly made biology feel like an adventure, a fascinating world. That’s when things started to become clearer. I liked both biology and chemistry, but couldn’t choose between them. Biochemistry seemed like the obvious path. From there, I entered a captivating world. I’ve always been drawn to the invisible, the microscopic world, microbiology in a broad sense. As time passed, I began to narrow down my interests. From the start, cell biology held great appeal, that microscopic universe. It’s a world hidden from view, and that fascinates me, because there’s so much we don’t know, that we can’t see, but which helps us understand the macro. My interests eventually focused on cell division, a process that requires an extraordinary transformation at the cellular level. It’s a unique moment in a cell’s life that completely transforms it. Visually, it’s an incredibly appealing and attractive process because of microscopy. Images of dividing cells under the microscope are stunning. That aesthetic beauty drew me in, I’m very much someone who notices small details, and then feels driven by curiosity to find out more. So I realised it was an interesting problem and one I wanted to study because it was highly visual. The microscope was always my gateway into that world. And here I am doing Cell Biology and studying cell division for over 20 years.

You've been awarded the three main individual grants from the European Research Council (ERC), an absolutely remarkable achievement. Beyond the scientific merit and disruptive nature of your work, could you share with the U.Porto research community what philosophy you adopt when preparing a proposal for such a prestigious grant, and what challenges you've faced? Has the process become easier over time?
Contrary to what people might think, it has actually become more difficult. The three ERC grant levels are very different, and the demands increase with each one. When you’re starting out, a lot is forgiven, if you show potential, things can happen. But it's a clear pyramid: broad at the base, narrowing sharply as you climb. But I love challenges. The best thing someone can say to me is, “It’s not possible. You won’t manage.” When I returned from the U.S. and started my research group in Portugal, many colleagues told me, “It’s too hard here, there’s no funding…”, and that was the greatest motivation I could have received. We got the group going. The Foundation for Science and Technology (FCT) played a key role, enabling us to build on the initial investment. For me, it’s vital to see the question — and it has to be interesting. Not just to me, but to you, too. If it isn’t, it comes across as obscure, a detail only of interest to specialists. And that’s not what fundamental questions are about, they should resonate more broadly. Like: “Why is the sky blue?”, a question we’ve all asked at some point, without necessarily getting a clear answer. There’s no secret formula. Our research group is celebrating 20 years, and the latest ERC project we submitted, and won, was the hardest I’ve ever written. It pushed me far outside my comfort zone. After 20 years of work, I asked myself: “Now what? What do I really want to do?” I’ve always set the bar high, and made that clear to my team. Once we won the first ERC Starting Grant, we committed to working towards the next one. And we did.
When that happened, I told my group that I didn’t want to feel pressured to win a third, because that pressure could distort the process. It can become addictive, a kind of vicious cycle, and that shouldn’t be the motivation, even if in our scientific adolescence we feel we want everything. Ambition is important, but experience brings a kind of maturity, and we start to realise: it doesn’t have to be like that. We wrapped up the Consolidator Grant six or seven years ago, and for two years I didn’t apply for anything else from the ERC. Because I didn’t have the right question. One of the few strengths I think I have as a group leader is strong intuition, knowing what might work and being able to see the path clearly. Last year’s Advanced Grant happened largely thanks to the privilege I have of working with people who are smarter than I am, which is incredible. It’s enriching and you learn so much. I’ve had the good fortune to be surrounded by these people, who collectively helped me see what the next step should be. Often it starts with an idea that someone new to the group brings in, and I try to help it take shape and grow. That was key for this latest project: ten years of working with a rather unconventional model, which turned out to be our trump card. It’s a powerful model that, I believe, no one in the world understands better than we do. That gives us real potential to address fundamental questions. It’s important to remember that what the ERC values is the question, the advancement of knowledge. That pure, foundational kind of knowledge, which is becoming increasingly undervalued these days. When I say “fundamental questions,” I mean ones that build the pillars of knowledge. If we establish this pillar, what can we learn? From a practical standpoint, when I write projects I vanish from the world for two or three months, fully immersed in ideas, concepts, and literature, until I feel I’ve reached that point where the project might win. That’s all we can do: submit a project that might win, and then fight for it. But it’s exhausting. It really takes a toll. I’m still recovering from the mental fatigue of putting together a proposal of that calibre, it has to be perfect, or close to it, because the competition is fierce.

Your scientific work is driven by the exploration of the mysteries and mechanisms of cell division, research with potentially crucial clinical applications in cancer treatment. Could you tell us more about your current Advanced Grant project, its origins, the big question it seeks to answer, and the path your team is following toward a conclusion?
The core theme, the biological problem, remains cell division. It’s been the focus of all three ERC grants, and it has been the centre of my work ever since I became a scientist. I believe our strength has always been our ability to look at the problem from unusual angles. In our previous grant, we began exploring the impact of microtubule diversity, a 40-year-old concept whose true significance was still unclear. After twenty years of global research into this problem, not just by us, but by dozens of labs, we’ve now reached a privileged position where we can start asking questions about biology’s biggest mystery: evolution. That’s the big one. There are theories, yes, but we still lack experimental demonstrations of how things actually progress. We’re studying two species of deer that are genetically very similar, so much so that they can interbreed and produce viable, though sterile, offspring. One species has 46 chromosomes, and the other has just 6 (in females). This raises the question: if both species function well, does the number of chromosomes even matter? Why does one have 46 and the other 6? Is there an advantage to having only 6? A disadvantage? Or is it totally irrelevant? Take Homo sapiens, for example, we have 46 chromosomes, a result of a fusion between two chromosomes in other hominids (like chimpanzees, orangutans, and gorillas), who have 48. For decades, it was assumed that humans also had 48 chromosomes, only later, with advances in cytogenetics, did we discover the true count. So: is there an evolutionary advantage linked to having 46 chromosomes? Could this change have contributed to our emergence as the dominant species? These questions go on and on. But we’ve chosen to focus on what we know well: cell division. We started looking at questions connecting chromosome number and cell division. We often discuss evolution in terms of genetic changes, DNA sequences that shape morphology and distinguish species. But what about the in-between, the cellular level, where those genetic changes need to be accommodated and translated? So while our work is still centred on the cell and cell division, we now want to understand whether specific genes must evolve to cope with having just 6 chromosomes, for example. That’s the heart of the question: how do dividing cells handle variations in chromosome number? This also connects to cancer, because changes in chromosome number are the single most common feature across all cancer types. At some point, nearly every cancer undergoes chromosomal changes. It might not be the cause, but it does happen. In speciation, these changes take millions of years to settle; in cancer, it all happens within a person’s lifetime. We believe both processes, evolution and cancer, share underlying mechanisms. The difference is that cancer doesn’t have time to adapt. If we can uncover genes or mechanisms that allow cells to cope with altered chromosome numbers, we might be able to use that knowledge in treating cancer, where such changes are widespread. There are already clinical trials targeting chromosomal instability in cancer, but we still don’t fully understand why those cancer cells are more vulnerable to these treatments than healthy ones. What we’re aiming for is more targeted treatment, something that acts specifically on harmful cells, while sparing healthy ones. And that’s the big issue with cell division: for better or worse, our cells have to divide.

Are we one step closer to understanding the genesis of our origin as a species, or are we still light-years away in our knowledge of our own evolution?
That’s an interesting question. I believe we are closer. I think we, as humans, tend to see ourselves as superior to everything, to all other species. Our dominance on the planet is a reflection of that. Curiously, one area that has progressed significantly in recent years is the sequencing of hominid genomes, other human species, not Homo sapiens, but close enough, that were part of the emergence of modern Homo sapiens, and which provide us with clues as to how that evolution happened. We now have the code, and for the first time, which would have been unthinkable just a few years ago, thanks largely to improved methods for extracting biological material from remains found across the world, we’ve been able to reconstruct a map of how it all began: interbreeding between two species that led to the appearance of others, the composition and part of our genome that may have evolved from a dominant or a less dominant species. Today, we are closer than we were just a few years ago to understanding our origin. I recommend a very interesting book by a Harvard professor named David Reich, who works in this field. It’s called "Who We Are and How We Got Here" and is aimed at a general audience. This is an emerging area that has helped transform recent scientific knowledge. In fact, Svante Pääbo, a Swedish scientist and pioneer in the ability to preserve and extract DNA from these human-related species, was awarded the Nobel Prize for this work. His research has allowed us to understand a little more about our origins and how we got to where we are today. It’s increasingly less about theory and hypotheses, and more about evidence. Previously, we relied on anthropological data, fossil records, even the capacity to make and use tools. Nowadays, we have genetic information that lets us imagine what things were like thousands of years ago. We have genetic data, we have the DNA of those individuals, and can understand how, from that point, we evolved to where we are now, and what contribution a certain subspecies made to today’s Homo sapiens. We are now closer, because we have this priceless, invaluable material: biological samples and remains that we’ve been able to preserve and extract information from. All of this speaks to our past and how we arrived at the present. Interestingly, the genes that evolved most rapidly between Neanderthals and Homo sapiens are those involved in cell division. It’s thought this may relate to the efficiency of precursor neural cells, meaning we may have been able to form more neurons because we have those mutations in genes that are important for dividing neural precursor cells. It’s fascinating.

We are closer to answering these questions thanks to scientists and researchers working in the field. In 2016, you were elected by your peers to join the European Molecular Biology Organization (EMBO). Considering that experience, in your view, does Europe invest enough in science? There seems to be a certain superficiality in what’s communicated to the public. Is there a political and societal awareness of the importance of science? What more can be done to draw society’s attention to it?
The answer is quite simple: better education, different education. But that takes time, and it doesn’t have immediate results. The logic of science and the logic of communication are very different. Science is profoundly deep, it seeks to understand foundations, mechanisms. Communication wants what’s visible, what reaches people. And what reaches people is a vaccine that solves a pandemic, a revolutionary medicine that cures cancer. But then we forget to consider how we got here. Human ingenuity allows us to create solutions, solutions we often don’t know the use for at the time, but that, in a very specific context, become transformative. Everything that was behind solving the last pandemic was fundamental science, from diagnostics, to rapid tests, to vaccines. I believe what has set the most developed countries apart is their understanding that the innovation cycle depends on a very broad base of fundamental science. Without that base, there’s nothing to fuel the fire that eventually gives us timely results, when challenges arise, and we need to respond. That’s when experimentation starts, when we transform knowledge into something useful. In Europe, the ERC initiative is unique in the world. Curiously, many projects funded by the ERC wouldn’t stand a chance of being funded today in the US. What the US represented 20 years ago, and I’ve been there too, was freedom to explore, to experiment without constraints. That’s gone. Not entirely, but it has been significantly reduced. Europe has made that effort, but it’s still limited. What’s done at a European confederate level doesn’t always translate into national policies. Portugal has stopped investing in fundamental science, this is very clear. And if we look at wealthier countries, Switzerland continues to fund top-level basic research. Germany, despite economic slowdowns, remains one of the countries that understands the importance of investing in fundamental science. Because when that cycle ends, we’ll stop feeding the pipeline that leads to visible innovation. At the European level, the hope is that scientific communities can still have a voice, but it’s getting harder to be heard in EU politics. We live in reactive times, with less strategic vision. I have no miracle solutions. What I would always do is give as much freedom as possible to people who have already shown great ability to ask the right questions and find the answers. Linking something to practical use is easy, what’s hard is having the original idea.

From a national perspective, Portugal has far more limited resources. Between 2012 and 2015, you were National Adviser for Science and Technology to the Prime Minister. From that structured perspective, and given what you know of the landscape, do you believe there is an opportunity for scientists and researchers to have a more active voice in politics and how society is managed?
If we go back 20 years or more, we can see how science was transformative in Portugal. There was a moment when we went from having no science to having the most qualified generation ever, if we may use that phrase. In fact, science is probably a case study; it was certainly the most transformative area in our society since it emerged. Why? Because we invested in education. When you say Portugal lacks resources, I both agree and disagree. We don’t have significant financial resources, but we have something of immeasurable value: people. People hungry for knowledge, people who were deprived of it for decades. People who are incredibly motivated to progress, if given the chance. We started our research group with €10,000, and today we’ve been able to attract €11 million, not including the individual salaries for the 40+ people who have worked in my group over the last 20 years. Science is a good investment if it’s done properly, based on merit, with transparency and peer review. The data is there, it’s not my opinion. Every euro invested in science has been worth hundreds or thousands of times more for our society: in terms of knowledge production, the training of highly qualified generations, and all the indirect benefits orbiting around science. I speak objectively: the numbers are there, studies exist. Science has been a serious success story, largely thanks to the vision of someone called Mariano Gago, who dreamed of a different country, didn’t give in to the "we’re too small" mindset, and believed we had equal or greater potential for scientific growth and transformation. That gave rise to my generation, which benefited from these policies, and they cannot be confined to short-term political cycles. They also stemmed from a long period of political stability: Gago was Minister for Science across four terms and had time to implement a coherent, long-term vision. Science needs time. Every time a politician tries to tinker with the system, I sometimes ask them not to, because they're more likely to ruin it in the name of short-term transformation. I’m a strong advocate for the independence of scientific bodies linked to governments. I believe they should be depoliticised and led by the scientific community itself, through the leaders it elects, with budgets that are negotiated but autonomous. That, to me, is very clear. I’m an optimist and I believe we’ll get there. We live in turbulent times, hard to understand or accept on many levels. And science may seem less important when people are dying in wars that have once again become part of our daily lives. That’s why science has disappeared from the headlines, but it’s still part of the solution, in many ways. We’re about to enter a new revolution with artificial intelligence, and we must be prepared. The more literacy we have in that field, the more prepared we are to coexist with it, the better positioned we’ll be in a globally competitive future. I believe social sciences can help us respond to these challenges, and they’re often science’s poor cousin. Perhaps they’re even more transformative, at least in the short to medium term, but they are deeply neglected. I’m not a social scientist, but I’m the first to say it: social sciences are a crucial pillar that has been ignored for far too long by policymakers. Often, the direction is already clear from existing studies, and we end up going in the opposite direction. Still, I want to believe that at some point, the light will shine through. Common sense will prevail. And eventually, we’ll have to act. It’s curious: when a country faces a financial crisis, they call in a technocrat to fix it, someone from the scientific world, to make evidence-based decisions. We must move away from experimentalism and from solving problems in poetic or ideological ways. It’s time to re-embed scientific culture in our society.

You are the founder of Yscience, a non-profit initiative aimed at instilling a passion for discovery in children by encouraging them to explore the wonderful world of science. What motivated you to create this project?
Today's school system still teaches based on post-Industrial Revolution principles, even though curiosity, creativity, and critical thinking are increasingly seen as the most distinctive traits for a near and rapidly approaching future. These aspects are not fostered in the current educational system, which doesn't teach students how to ask questions, nor does it encourage them to do so. In fact, most teachers feel quite uncomfortable when students ask questions about things they themselves don’t know. Because supposedly, a teacher isn’t meant to not know something. That mindset needs to be dismantled. A teacher doesn’t need to have all the answers, they should try to find them together with the students. Saying “I don’t know” is a great starting point for working with pupils. Yscience was born as an act of rebellion. I asked myself: what can I do, what is within my reach to help change the course of education? I often say that all children are born knowing how to ask questions, but school continues to teach them how to give answers, it doesn't teach them to question. And the name Yscience (“Y” homophone word of why) stems exactly from this: Why? The whys of children, who are always trying to find out, always asking questions, and they are the most interesting questions because they are innocent. Something has struck them, and they’ve become curious. Coming from a science background myself, and my wife being a psychologist who works with children, we looked at the schools, we looked at our own kids, and we saw a gap. That’s when we decided to start this project. I should stress, it is a non-profit initiative. It’s privately run, and I want it to stay that way. I want to remain in control and decide what direction it takes. I don’t want anyone telling me how to do this. I don’t want to depend on public funding or grants. We work with local councils, with schools, both public and private, and with anyone who wants to collaborate with us. That’s our philosophy. The idea is to explore the scientific method within a school setting. It’s really that simple. It's a method that has withstood 2,000 years of testing and remains crucial in the learning process. Formulating a question, developing a hypothesis, deciding how to test that hypothesis through an experimental approach, and being able to analyse the results. And very often, those results don’t answer the original question, they raise new ones. My impression nowadays is that school has slowly killed off this entire cycle, and we’re trying to keep it alive. Fortunately, there are many schools that agree with us, people with vision, who we’ve been working with, even integrating our approach with their academic curricula. We’re not talking about after-school clubs; we’re talking about teaching science by doing science, setting aside regular weekly time so this way of thinking and working becomes a habit, and so that students begin to approach problems differently. Thankfully, we’ve probably already worked with thousands of children who have soaked up this spirit. Our resources are very limited, and I’m aware that I can’t dedicate much time to the project anymore. In the beginning I did, but now I’m just behind the scenes, the project runs on its own. We have paid staff, no volunteers. I don’t like having volunteers working, I prefer to have people who are compensated for what they do. All of this comes at a cost, in the name of the project’s sustainability and independence. That’s an important point too: if we depend entirely on public funding, we’re at its mercy. When that’s no longer possible, the project will end, at least with me involved.

Science is born from insatiable curiosity. What questions are you still hoping to ask?
I don’t know what they are yet. But I’m sure they’ll come. Right now, the questions that keep me up at night are the ones we’ve talked about during this interview, they relate to the next 5 or 6 years, a horizon for which I already have secured funding, and which will allow me to dedicate most of my resources and efforts to these questions that are already defined. I’m also quite pragmatic. I don’t like getting distracted too early. I’m very focused, almost obsessively so, when there’s a question that’s been identified. What 20+ years of experience have taught me is that five or six years from now, I’ll have new questions. The big issue is whether I’ll still have the energy to pursue those answers. As for what the future holds, I don’t know. But at least up to this day, I’ve always been driven by the desire to solve these questions. And I think one of the things I’ve managed to do, sometimes at a cost in other areas, is to work out what really matters. To distinguish what’s truly important from what’s secondary, so I can give my time to it. In this respect, I’m a bit selfish, I’d even say quite selfish, because I always put the focus on the question that’s haunting me at that moment. Often that’s at the expense of helping solve more immediate, practical problems around me. Not that I don’t try, but as long as I can live with this kind of selfishness, in a good way, where I still have the chance to pursue my own questions, that will remain my focus.

You can find more information on the researcher and professor here.