ABSTRACT
Caroline Mauvezin is a group leader at the Faculty of Medicine and Health Sciences, University of Barcelona, Spain. She completed her doctoral work with Antonio Zorzano at the Institute for Research in Biomedicine (IRB) in Barcelona, studying the role of the transcriptional cofactor TP53INP2/DOR in autophagy. She subsequently moved to Thomas Neufeld's lab at the University of Minnesota, where she investigated the role of proton pump V-ATPase in autophagosome–lysosome fusion events. After moving back to Spain to the Bellvitge Biomedical Research Institute (IDIBELL) for a postdoc under the supervision of Albert Tauler, Caroline established her independent research group in 2021 at the Department of Biomedical Sciences in the Faculty of Medicine and Health Sciences, University of Barcelona. Her lab studies the role of autophagy and lysosomes in cell cycle progression and in the prevention of chromosomal instability. We spoke with Caroline over Zoom to learn more about her career path, her approach to mentoring and how cooking inspired her passion for experimenting.
Caroline Mauvezin. Photo credit: Marta García-Cajide
What inspired you to become a scientist?
I was always a very curious child, and I loved to experiment. My passion for experimenting began in the kitchen, where my mom, who is a great cook, encouraged us to play and create. This exposure sparked my interest in the link between food and health. I have always believed in the power of nutrition and its impact on wellbeing, which laid the foundation for my later studies. When I discovered cell biology, I became fascinated by the complexity and functionality of cells. The idea that a cell, the smallest unit of an organism, is capable of such intricate processes still amazes me.
How did you choose what to do and where to go for your PhD?
It took me quite a while to find what I wanted to do. From the beginning of my university studies, I knew I wanted to pursue something related to biomedical research. I initially began studying medicine, but I soon became more interested in research and realised I didn't want to be a medical doctor. I began to explore biotechnology because it combined elements of food quality and health, and eventually I realised I wanted to focus on cell biology when I had the chance to work in a lab doing cell culture and studying cell metabolism.
I started my PhD in 2006 in the laboratory of Antonio Zorzano at the Institute for Research in Biomedicine (IRB) in Barcelona. The IRB was then in its early stages, making it a vibrant and exciting place to work. Antonio's lab focuses on metabolic diseases, specifically type 2 diabetes. My PhD project started by following up on an observation made by a former PhD student that a transcriptional cofactor named TP53INP2/DOR was present in the cytosol, which was unexpected because transcriptional cofactors are typically found in the nucleus. TP53INP2/DOR had initially been studied in the lab because its expression had been shown to be markedly repressed in muscle from patients with type 2 diabetes, therefore linking it to metabolic diseases. We discovered that this cofactor interacts with the autophagic machinery, which led me to study autophagy and opened up an exciting new line of research in the lab. At that time, the lab lacked expertise in autophagy, so I attended many international conferences to learn about this field. It was challenging but also very interesting. I grew to love the process of autophagy, which plays a crucial role in maintaining cellular homeostasis. This aspect of autophagy fascinated me and it became a central focus of my research.
Following your PhD at the IRB in Barcelona, you moved to the Department of Genetics, Cell Biology and Development at the University of Minnesota to join Thomas Neufeld's lab as a postdoc. What prompted this move?
Some people might not consider Minnesota the most appealing place to move to, but we had a wonderful time living there, and the University of Minnesota is one of the most highly ranked universities in the USA. I knew I wanted to continue working on autophagy, but I was eager to explore different model systems, such as Drosophila. I had the opportunity to meet Tom at a conference, and I was captivated by his approach to science. Drosophila offers a neat way to investigate cellular processes, and I loved that I could study genetically modified cells alongside wild-type cells in vivo in intact ‘mosaic’ tissue. Additionally, Drosophila research involves a strong component of microscopy, which has become critical in my professional career, as I really enjoy being able to directly observe cellular processes with my own eyes.
You returned to Barcelona to do a postdoc with Albert Tauler at the Bellvitge Biomedical Research Institute (IDIBELL), where you were awarded two prestigious fellowships: the Juan de la Cierva Fellowship and the Marie Skłodowska-Curie Individual Fellowship. What was the significance of these fellowships for you?
My return to Spain was motivated by a desire to apply my knowledge more directly to understanding pathology. I joined the Metabolism and Cancer group at IDIBELL, a cancer research institute in Barcelona. At this stage of my career, I knew that in order to successfully continue working in academia I needed to secure fellowships to strengthen my curriculum vitae. The fellowship applications required a lot of work and studying, but it was worth it. I received the Juan de la Cierva Fellowship from the Spanish government shortly after I joined the laboratory of Albert Tauler. My research focused on the role of lysosomes in cell invasion and migration. I was particularly interested in how the positioning of lysosomes could influence these processes in cancer cells. This work was fascinating, and through it, I indirectly observed an atypical ‘toroid’ nuclear phenotype characterised by a donut-shaped nucleus. I was intrigued by this phenomenon and wanted to learn more. This discovery formed the basis for the project I proposed for the Marie Skłodowska-Curie Fellowship, which I was subsequently awarded.
What are the main research questions that your lab addresses?
We have two main research lines. The first line focuses on the function of autophagy in cancer cell division. Autophagy is a catabolic process typically occurring in the cytoplasm. Surprisingly, little is known about the role of autophagy during mitosis, during which the cytosolic components can be in direct contact with the nuclear components upon the breakdown of the nuclear envelope. We are specifically interested in understanding how autophagy is regulated during mitosis, as we have previously shown that autophagy and lysosomes protect against chromosome mis-segregation and chromosomal instability. This is highly relevant in the context of cancer, where cells are known to become chromosomally unstable and highly proliferative. Our second line of research centres on a nuclear phenotype we refer to as the toroidal nucleus, which is a donut- or ring-shaped nucleus. We are dedicating significant energy and effort to bringing this phenotype to the attention of the scientific community. The toroidal nucleus is associated with chromosomal instability, a hallmark of cancer. Therefore, understanding this phenotype is crucial in cancer research for fully grasping the characteristics of chromosomal instability in cancer cells.
Toroidal nucleus, a marker of chromosomal instability. The image shows a confocal z-stack maximum-intensity projection of osteosarcoma U2OS cells stained with DAPI (magenta) to detect the presence of toroidal nuclei. Lysosomes were detected by using a LAMP2 antibody (yellow), and actin fibres were stained with phalloidin (cyan).
Toroidal nucleus, a marker of chromosomal instability. The image shows a confocal z-stack maximum-intensity projection of osteosarcoma U2OS cells stained with DAPI (magenta) to detect the presence of toroidal nuclei. Lysosomes were detected by using a LAMP2 antibody (yellow), and actin fibres were stained with phalloidin (cyan).
Looking back at the beginning of your independent career, what challenges did you face when starting your lab?
My transition into the role of principal investigator (PI) has been a little unconventional. I was honored to be awarded a highly competitive grant from the Spanish Ministry of Science. Receiving this grant essentially marked the beginning of my role as a PI. However, I needed to be hosted by another lab. Luckily, I found a great fit in the Department of Biomedical Sciences at the University of Barcelona with Neus Agell. The first few years were challenging, as I had to secure additional funding to establish myself. One piece of advice I received that I found very helpful was not to rush the process of setting up a lab. It is a long and complex journey. Something that greatly supported me during this time was the confidence Tom Neufeld expressed in me when I left his lab. His belief in my ability to take on this role was incredibly important and reassuring. Additionally, finding support both within and outside my institution has been crucial. I am part of several associations, including the Spanish Association for Cancer Research (ASEICA) and Women in Autophagy (WIA). Being involved in these groups has been an amazing experience. I am currently serving as the co-chair of the WIA mentoring committee. This role has been incredibly enriching, providing valuable opportunities for organising focused mentoring workshops to support communication and networking alongside other scientists facing similar challenges.
Everyone makes mistakes – it's part of the process and how you learn. I encourage openness and respect because I know that transparency leads to solid science.
What advice do you give to your lab members?
Research is really a team effort, and I don't believe in strict hierarchy. I have thought a lot about my lab's philosophy and have found that the human factor has always been very important in all the moves I have made in my professional career, so this is something I pay close attention to. Trust is the foundation of my lab. I need to trust the people I work with, and I ask my lab members to be transparent. Everyone makes mistakes – it's part of the process and how you learn. I encourage openness and respect because I know that transparency leads to solid science. We focus on basic research because I believe that understanding fundamental cell biology is essential to building a strong foundation for successful clinical applications.
How do you get the most out of the meetings you attend, particularly in the early stages of your career?
What I enjoy most about meetings is talking to people. It's not just about networking or establishing collaborations; it's about engaging with others about their projects. I enjoy participating in discussions, linking different areas of expertise and building something collectively. I actively encourage my students to do the same, even if it can sometimes be challenging. To help my students overcome their hesitations, I strongly encourage them to attend both national and international conferences. This has been incredibly helpful for me in my career, and I want them to have the same opportunities.
I believe the key aspect is visibility – more visibility helps show people who are underrepresented in science that leadership roles are possible for them
What do you think is needed to help more women and underrepresented researchers take up leadership positions in science?
This is a very challenging question and I'm actively trying to contribute to addressing it. I believe the key aspect is visibility – more visibility helps show people who are underrepresented in science that leadership roles are possible for them. That's what we aim to do at the WIA network as well as at the ASEICA and other cancer research associations. Every year, I participate in science communication programmes and visit primary schools to talk about science in order to help ‘break the glass ceiling’. Whilst not every child might be interested in science, if even one or two are inspired, it makes it worthwhile. It's all about demonstrating that pursuing a career in science is possible if you are enthusiastic about your work.
If you could change one thing in academia, what would it be?
Currently, the most frustrating aspect of academia for me is the pressure to publish within the short timelines of grant-funded projects. Additionally, the publication process can be very frustrating, although things are gradually changing. The Company of Biologists and other publishers are doing an excellent job in addressing these issues, but overall there is still a long way to go. The pressure of ‘publish or perish’ can be overwhelming and can cause a risk of rushing and compromising the quality of the data and overall science, which is something I would never accept.
Could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?
I still enjoy cooking and continue to experiment in the kitchen at home. I'm also the happy and proud mother of three outstanding kids. I had my first child early on in my PhD. This was very challenging, but it also taught me how to balance my responsibilities very quickly. Somehow, every move I made in my career coincided with welcoming another child, but academic work has given me a lot of flexibility, which has been crucial for balancing my professional and family life. I enjoy working, and at the end of the day when I come home, my kids help me disconnect from science and focus on other important aspects of life.
Caroline Mauvezin's contact details: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
E-mail: [email protected]
Caroline Mauvezin was interviewed by Sara Morais da Silva, Reviews Editor for Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.