Interview with Associate Editor Pedro Carvalho

Pedro Carvalho

What inspired you to become a scientist?

There wasn't a single moment where everything just clicked. I've always been interested in biology and in understanding how things work. From a young age, it was clear that I would pursue something related to biology. However, my passion for research developed gradually, shaped by several key influences. One major influence was a book I read by June Goodfield about the story of the renowned Portuguese scientist Maria de Sousa. The book, ‘An imagined world: a story of scientific discovery’, fascinated me. I read it just before starting university, and it deeply resonated with me. It didn't just describe her scientific work but also captured her emotions and experiences during the research process. The constant search for answers, the setbacks and the triumphs were portrayed like a detective story. That narrative truly sparked my imagination and made me believe I could become a scientist. Interestingly, Maria de Sousa would later play an important role as a mentor in my academic journey during my PhD.

Can you tell us about your career path so far? What has been the most interesting stage of your scientific career?

I studied biochemistry in Coimbra (Portugal), but after graduating I moved to Porto (Portugal) to work in the laboratory of Claudio Sunkel (Institute of Molecular and Cellular Biology, Porto, Portugal). Later, I was accepted into the Graduate Program in Areas of Basic and Applied Biology (GABBA), a prestigious Portuguese PhD programme, that offered students the opportunity to do their research in labs around the world. Through this programme, I joined David Pellman's laboratory at the Dana-Farber Cancer Institute (DFCI, Boston, USA). My research focused on the role of proteins that localise to the plus ends of microtubules in controlling dynamic instability during cell division. During my time at DFCI, we held joint journal clubs with research groups from Harvard Medical School, where I met Tom Rapoport. He persuaded me to join his lab for a postdoc, and I shifted my research focus to protein quality control and organelle biogenesis. I embraced this challenge and thoroughly enjoyed the work. After five and a half years, my wife and I had started a family – one child and twins on the way – so we decided it was time to move back to Europe to be closer to home. I secured a position at the Centre de Regulació Genòmica (CRG) in Barcelona (Spain), where I worked from 2010 to 2016. CRG was an incredible place to transition into running my own lab, offering excellent funding and resources that allowed me to focus entirely on research. I was fortunate to recruit a talented team early on, which was instrumental in driving our work forward. However, the position was not tenure track, which prompted me to move to the University of Oxford in 2016. This transition opened up new directions for my lab. Although our previous research focused exclusively on budding yeast, at the University of Oxford, we expanded into mammalian cells, high-throughput screening and, through collaborations, to other areas such as structural biology. This diversification has been incredibly exciting and intellectually enriching. Every stage of my career has been unique and transformative, shaping me as a scientist. If I had to highlight one pivotal moment, it would be the transition to running my own lab. It required me to develop new skills, adapt quickly and embrace the challenges of leadership.

What ultimately drew you toward studying organelle biogenesis?

The shift to studying organelle biogenesis happened during my postdoc with Tom Rapoport. His lab was an exceptional environment for developing my interest in membrane biology, thanks to Tom's expertise in protein biogenesis and quality control, and his biochemistry-driven approach to science. I was fortunate to join his lab at a pivotal moment when they had just discovered that misfolded proteins in the endoplasmic reticulum (ER) are transported back into the cytosol for degradation by the proteasome. At the time, although genetic studies had identified some components of this pathway, the field lacked a clear understanding of how the process was organised and the specific roles of its key players. I wanted to understand not just the molecular mechanisms underlying these processes but also how they integrate into broader cellular organisation. My work focused on how ubiquitin-dependent protein degradation regulates organelle function, particularly ER function. Our research revealed that ER-associated degradation (ERAD) is organised into distinct ubiquitin ligase complexes, each specialised in recognising different classes of misfolded proteins. These findings provided a solid conceptual framework for understanding the ERAD pathway, unifying scattered observations into a cohesive model. This work was pivotal in shaping my scientific interests. It solidified my fascination with the complexity and functionality of the ER, an area I wanted to explore further.

What is the main theme of your lab's research and what questions are you trying to answer just now?

My lab currently focuses on two main research areas. First, we aim to understand how ubiquitin-mediated degradation regulates ER function. Specifically, we study how ERAD targets membrane substrates, the mechanisms of membrane protein quality control, membrane substrate preferences, the molecular basis for recognition and how proteins are translocated to the cytosol for proteolysis. Our second focus is on lipid droplet biogenesis. We investigate the molecular mechanisms that govern the lipid droplet formation and their interactions with the ER membrane. Lipid droplets are unique because, unlike other organelles with bilayer membranes, they are surrounded by a monolayer of phospholipids. Moreover, they originate at the ER – a bilayer organelle gives rise to a monolayer structure. Both projects are incredibly exciting as they address fundamental questions about how organelles form, function and maintain cellular health.

What do you think are the biggest open questions in your field?

We already have substantial knowledge about many aspects of ER biology, such as protein targeting, translocation and folding. However, our understanding of quality control mechanisms remains far more limited. For instance, although we know many of the components involved in clearing proteins once they've been selected for degradation, the mechanism of selection itself remains elusive. How do cells determine that a protein is defective or surplus? And how are defective or unnecessary proteins identified in the first place? Similarly, another major gap lies in our understanding of membrane protein extraction. Although we have substantial knowledge about how proteins are inserted into membranes, we know much less about how they are extracted. Compared to the well-established domain of protein biogenesis, the field of quality control is still in its infancy. These are major challenges for our field, and we hope to make significant progress in addressing them in the coming years.

What elements, inside or outside the lab, have been key to your success in science so far?

The most important element of my success has undoubtedly been the people who have worked with me. They are the ones who believed in our ideas and put them into practice. Since I started my lab, their dedication and hard work have been essential.

Early on, I realised that I couldn't spend much time at the bench, so my role shifted to training lab members on key aspects of research while they took charge of driving the projects forward. Their ability to execute and innovate has been critical to the lab's success. Another vital element has been funding. Access to adequate funding has enabled us to pursue bold experiments, which has made a big difference. It's difficult to take risks and aim for significant discoveries when resources are limited. Finally, resilience has been a key personal trait that I believe has contributed to my success. Science is full of challenges, and the majority of what we attempt doesn't work – sometimes as much as 80% or more of our experiments fail. Resilience allows you to persevere, explore alternative approaches and remain motivated. Without it, it's easy to feel stuck or defeated. Outside the lab, my wife has been an incredible source of support. We started this journey together, and she transitioned to industry, becoming a project manager in a biotech company. Spending time with her and our kids has been essential for maintaining perspective and staying energised. Being able to step away from science, even briefly, has been vital for my mental well-being.

What advice would you give to young scientists developing their careers?

There isn't a single recipe for success in science. There are many paths to achieve it, and what works for one person might not work for another. That said, I believe there are key elements that are essential, one of which is resilience. Science is full of challenges, and setbacks are inevitable. Experiments often don't go as planned, and progress can sometimes feel slow. Resilience helps you to push through those moments, adapt to obstacles, and keep moving forward. Also, to have passion for what you do is essential. You must enjoy doing science. If you're not having fun or feeling excited about your work, you might need to reconsider whether you are in the right field. Science can be fantastic and deeply rewarding, but it also comes with its share of frustrations. Passion keeps you motivated during tough times and allows you to fully appreciate the highs. So, my advice boils down to this: be resilient and have fun. Find joy in the process of discovery and problem solving. If you're passionate and persistent, the challenges become part of the journey rather than obstacles in your way.

If you could change one thing in academia, what would it be?

There's been a lot of discussion about the challenges facing academia, such as lack of diversity and inclusivity, limited funding and low salaries. However, I believe these issues are not exclusive to academia; they are broader societal problems. Addressing them solely as ‘academic problems’ might not be the most effective approach. Instead, we should tackle them as part of a larger effort to improve societal structures overall. That said, I recognise that these are deep, systemic challenges that are not easy to resolve. However, focusing solely on academia risks missing the bigger picture. As for academia itself, I don't have major criticisms. One area that could improve, though, is the pace of change. Universities, for example, often evolve at a glacial pace, deeply entrenched in tradition and resistant to change. Although stability has its advantages (too much rapid change can be disruptive), the bureaucracy involved in making even small improvements can be exhausting, and the energy required to initiate change can feel overwhelming.

What made you interested in taking on the role of Associate Editor with Journal of Cell Science, and what impact would you like to make in this role?

The reason I decided to accept this role is threefold. First, I want to increase the visibility of research in membrane organelles and cell organisation. Journal of Cell Science is an excellent platform for this, and I'm enthusiastic about promoting this area of research through such a reputable journal. Second, I have previously taken on editorial responsibilities with other journals on a sporadic basis and genuinely enjoyed the experience. Such editorial roles allow me to engage with science I might not otherwise encounter, which is both stimulating and enriching. Although this might seem like a somewhat self-serving reason, I believe it ultimately benefits both me and the journal by broadening the perspectives brought to the editorial process.

Finally, I see this role as an opportunity to give back to the scientific community. JCS is a non-profit organisation with a mission to support young scientists and advance the field in meaningful ways. I greatly admire its ethos and look forward to contributing to its goals. Joining this project feels like a meaningful opportunity to make a positive impact.

It's increasingly difficult to keep up with the huge volume of scientific literature. How much do you read, and how do you choose what you read?

I don't read as much as I would like – there just aren't enough hours in the day! I try to focus on papers that are directly relevant to our work, but I also make an effort to explore broader topics when possible. Every other week, we hold a journal club in the lab, which is a great way to discuss papers related to our research and stay updated as a group. It's not just about my own reading; I also encourage everyone in the lab to read widely and share important findings with me. This collaborative approach helps filter the overwhelming amount of new literature and ensures we collectively stay informed.

As a scientist in the field of membrane biology, I am also familiar with authors who consistently produce impactful work, and I make a point to follow their publications. Tools like Google alerts are helpful for highlight papers of interest. Despite these efforts, I often feel like I'm not reading enough. With the sheer volume of new research, it's impossible to keep up with everything. Attending conferences is another way I stay updated. I attend about five conferences a year, which allows me to see the latest developments, connect with others in the field, and gain insights that I might not get from reading alone.

What sort of papers would you like to see more of at JCS?

Many high-impact journals tend to favour papers that are overloaded with data – figures packed with numerous panels, extensive supplementary datasets and author lists stretching into the dozens. Although such comprehensive efforts have their place, I think there is immense value in publishing concise, focused studies. At JCS, we have the opportunity to highlight research that makes a single, compelling point in a rigorous and straightforward manner, without requiring an overwhelming volume of data or unnecessarily complex supplementary materials. I want to see high-quality science papers in JCS with clear, elegant and well-executed experiments that deliver solid, impactful contributions to the field. Ultimately, I want high-quality science to be published efficiently. This involves providing authors with a fair and constructive peer-review process, where a single round of revisions is sufficient to address the main concerns raised by reviewers. By streamlining the process, we can ensure a positive publishing experience for authors while advancing the field in areas such as organelle biology and cell organisation.

How would you like to see scientific publishing change in the future?

First, I think it's essential to uphold the credibility of science throughout the publishing process. Unfortunately, many journals publish poor-quality papers, sometimes with little to no peer review or with very lenient standards. When journals fail to conduct rigorous peer review, they compromise the integrity of the research field. I've encountered instances where papers, even in reputable journals, contained fundamental flaws that should have been identified during the review process. This issue needs to be addressed. One potential solution is the use of AI in peer review, but I remain cautious. While AI could streamline the process, it might also introduce new biases or unintended consequences. Technology can be a helpful tool, but it shouldn't replace the critical thinking and expertise of human reviewers. Ultimately, my hope is to see a system that raises the standard of published research while ensuring a fair and constructive experience for researchers striving to share high-quality science. While I'm not overly optimistic about rapid change, I believe it's important to keep working toward improving the system.

Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

One thing I discovered after moving to the UK is my love for cooking. It has become my main contribution to the family – I have taken on the role of the designated cook at home, and I absolutely enjoy it. Cooking allows me to disconnect from lab work for at least a couple of hours each day.

Initially, I stuck mostly to Portuguese dishes, but over time, I've become more adventurous. I've started experimenting with Asian recipes, and so far, my wife and kids have given their approval. My oldest daughter is a talented baker, which has inspired me to take on a new challenge – learning how to bake. I've heard that baking requires more precision than savoury cooking. With baking, you need to stick to a core structure, but I'm excited to give it a try. Cooking has become my way to unwind and explore creativity outside the lab.

Pedro Carvalho was interviewed by Sara Morais da Silva, Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.