An interview with Sebastian Lourido

Posted by , on 21 November 2023

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MiniBio: Prof. Sebastian Lourido is a tenured professor at the Whitehead Institute and the Faculty of Biology at MIT in Boston, USA. He began his studies in Colombia, and from an early age developed an interest for the natural world. Seeking versatility in his undergraduate degree, he went to Tulane, in the USA, where he studied two simultaneous degrees, in Biology and in Fine Arts. During this time, he worked as a young researcher on micro-crustaceans and tropical diseases for the first time. Following completion of his degree, we worked for two years at the Max Planck Institute for Infectious Diseases in Berlin. After this time, he returned to the USA, and joined the lab of David Sibley for this PhD, where he first investigated Toxoplasma gondii. He was awarded a prestigious fellowship to start his lab at the Whitehead Institute immediately after completion of his PhD. Since then, he leads a team focusing on the study of the Apicomplexan parasite Toxoplasma gondii, which also constantly develops methodologies for microscopy to enable the observation of different processes in these organisms and their hosts. Sebastian has received multiple accolades, including recognitions for his interdisciplinary research, and his mentorship skills. 

What inspired you to become a scientist? 

I feel I was always inspired by the natural world. Among the nicest memories I have from my childhood, I is walking on the mountains. My family had an estate (a ‘finca’) to which we would go on weekends. We had all sorts of animals, crops, and a mountain that was completely untouched, somewhat arid and with cactuses and different animals that you’d never find in a city. It felt like discovering a new world. At the same time, my mom had a lab of cytogenetics at Universidad del Valle in Cali and I would join her to go to the lab every now and then. Since I was very young, I learned how to use a microscope, and see chromosomes and cell nuclei, and she would explain to me how this microscopic world worked. All these ideas were already in my head since a young age. This led to my own imagination and conception of the world.   

You have a career-long involvement in cell biology, parasitology and microscopy. Can you tell us a bit about what inspired you to choose this path?  

I wasn’t able to decide right after high school, what to study. So I thought that studying in the USA was somewhat unique in that I wouldn’t have to decide what my degree would be from the very beginning. I went to Tulane right after high school to do my undergraduate degree. In Colombia, like many other places in Latin America and Europe,  University is really to give you the tools to find a job right away. So from the beginning you have to choose the degree (and the specialization). In the USA it’s a lot more open – you choose whatever you want, and you choose your Major in the 2nd or 3rd year. The classes are also much more versatile. So for example, I liked the arts too – graphic design, plastic arts, etc. And I really wanted to have the capacity to do both things: to work in a lab and work on Biology, and use my creativity for the Arts. So I studied two degrees simultaneously: a Bachelors in Fine Arts, and a Bachelor of Sciences in Cell and Molecular Biology. I spent lots of time both, in the studio, and in the lab. I had a great opportunity to work with Scott Michael and Sharon Isern in the School of Tropical Medicine in Tulane, and they taught me a lot of the bases of Molecular Biology, and how to work in a lab. They created a wonderful environment, where I acquired my first experiences on how to do vanguard science. 

My second project as an undergraduate focused on transgenesis and using viruses to modify the genetic material of other organisms including micro-crustaceans called Daphnia. At this point I became really interested in understanding interactions between microbes and animals, and this inspired me to seek possibilities of doing further research focusing on infectious diseases. I think that the discipline of ‘host-pathogen interactions’ is a point in science where many species converge and interact in ways that are really interesting. So when I finished my undergraduate degree, I wanted to work in a microbiology lab. I had the chance to join the lab of Arturo Zychlinsky at the Max Planck Institute for Infectious Diseases in Berlin, where I worked as a technician for two years. There I focused on bacteriology, and particularly on some Gram negative bacteria (Shigella and Salmonella) that have the capacity to enter different mammalian cells, and replicate within those cells. So I was already thinking about these types of pathological interactions. I then moved to the USA to start my postgraduate degree, at Washington University in St. Louis. In the USA you have the chance to do rotations through various labs before you have to pick one where you will do your PhD. Just like when I was younger, I still wanted to try new things, and learn many things, and explore many fields of research. So, I did one rotation in virology in the lab of Herbert ‘Skip’ Virgin, one in bacteriology in the lab of Jeff Gordon who was working on the microbiome, and finally, some people had suggested that I work with David Sibley, as he was working on cell biology and parasitology. I found David’s work in Toxoplasmafascinating and captivating, because I saw an integration of all sorts of concepts in evolution, in cell and developmental biology, in molecular biology, in pathogenesis – all accessible through this system of Toxoplasma. I realized just how little we knew and how little we understood about the cell biology of these parasites. With the help of microscopes one could clearly see the incredible things that these parasites do when they invade mammalian cells. I found this absolutely fascinating, and decided to do my PhD in that lab. That’s how it all started! 

It’s great though, you are well known for your artistic representations and graphic design as applied to science. Was this something you envisaged already as an undergraduate student?

I think it has certainly been a valuable tool in the toolkit I use for my work as a Biologist. I feel Biology benefits from the disciplines of logics and mathematics, but there is also an aesthetic part. This aesthetic part exists in the experiments themselves involving the natural world we observe, with the symmetry of concepts, and the images we acquire with microscopes. And in the way we present science which should convey the complexity of scientific research in a way that is easy to understand. I think my training in the arts has helped me in this visualization of the natural world, and it has certainly impacted the way we do research in the lab, and my own development as a scientist. 

You became a PI straight after your PhD. Can you tell us a bit about this experience?

I developed a new project in David Sibley’s lab, working on kinases that phosphorylate proteins after being activated by calcium, and which manage some of the fast processes occurring in the Toxoplasma parasite’s life cycles. When I was finishing my PhD I had many questions still open, and many things I still wanted to do. While discussing with David Sibley, he suggested that I should apply to a position whereby you can start your lab straight after your PhD. The Whitehead institute, since its foundation, it has had these key positions (1 or 2 per year), where they create a space for young scientists, straight after the PhD can create their own lab. The idea is that the Institute supports the development of these selected scientists for 5 years, and prepares them to lead their labs as faculty of a university. There are similar programs in UCSF, Princeton, Harvard, the Carnegie Institute, and others, which provide these opportunities for young scientists. In other institutes in the USA, there are no such established programs, but they also support young PhD graduates wanting to follow this route. You basically skip the postdoc, when as a PhD student you are ready to use what you have developed, to create an independent program of science. I don’t think this is for everyone though. There are people who want to learn new tools, or explore other areas of research. And in this case, perhaps it’s best to enter an environment which is well established and fully developed, to give access to these tools. The position I chose is a high risk position because you have to quickly develop your own scientific identity and obtain the results you need to apply for a faculty position. You also have to develop your leadership skills very quickly. You need to be able to do the scientific work, via leading a group. This is not easy. This teamwork requires a lot of guidance and mentoring and abilities that you don’t always develop during the PhD. So you have to develop these very quickly too. I think we all have areas of opportunity where we can grow, and I try to pay attention and be self-conscious as the where my deficiencies as a leader are, and where I could and should improve my capacity to lead my team. Each person who joins your lab is an individual, with different needs and different abilities, and each therefore, requires individualized leadership. There’s also the different levels of their career – some are undergraduate students, some are PhD students, some are postdocs, some are technicians, and again, each of these positions requires different leadership skills. Each of the members of my team has taught me something new. My philosophy of leadership is not that one size fits all, and everyone adapts to me. On the contrary. I don’t believe in uncompromising leadership. But it does take a journey to get to the point where I try to figure our what is the best way of leadership for each person I guide.  

Can you tell us a bit about your day-to-day work as group leader at the Whitehead Institute?

My first position at the Whitehead Institute was as a fellow (straight after the PhD)- the position was for 5 years, and at the end of these 5 years, I started applying to tenure track positions, and I applied to different places including the Faculty of Biology of MIT. After being accepted, I was given the chance to stay as a member of the Whitehead Institute, where my lab is based. All tenure track members of the Whitehead Institute are also members of the Faculty of Biology of MIT – it’s a requirement in order to be able to stay at the Whitehead Institute. Regarding what I do on any given day… I think the life of a PI is a bit schizophrenic  there’s always many different requirements. Sometimes I spend the day writing grants, other days reviewing papers, usually every other week I meet each of the members of my team to discuss their projects and give them my opinions about new ideas. We have lab meeting once a week, where we can discuss the projects and ideas of the different team members presenting their work. I also teach throughout the semester. I teach subjects like Infectious Diseases and Cell Biology to undergraduate students. So I need time to prepare the talks, and to meet the students to do other related activities. Every day is different. At the end of most days I walk aimlessly around the lab, to see what new things and discoveries I come by. I no longer have time to sit down at the microscope or at the bench. My lab is considerably big, so it’s a bit prohibitive to do this. Once a year, for the last 3 years, I have had the chance to teach in Woods Whole, in the Physiology Course at MBL. This is an Advanced Cell Biology course under the leadership of Nicole King and Dan Fletcher. This course focuses on discovering new aspects of cell biology in different organisms, particularly using techniques such as microscopy. This time does give me a change to work hand in hand with students and optimize new methods in microscopy. This is my one chance per year to return to the lab. But during the rest of the year, I’m mostly working ‘behind the scenes’. Every now and then, when the microscope or the mass spectrometer fail, I’m called and I might be able to help. 

Many of your students are now group leaders themselves. How do you feel about this?

I think seeing the development of this legacy is one of the most wonderful things about working as an academic scientist. You get to work very closely with the PhD students and postdocs for many years, so when they go out ‘to the world’ and establish themselves as leaders of their fields, this is very rewarding. They continue to evolve and grow, and to see what new directions they take as scientists, is really nice. They take some aspects of the ‘spirit’ of the lab, and continue innovating under this ‘spirit’ – it gives me the sensation that I’m participating in a much wider network of intellectual development and scientific connection and scientific discoveries. One of the main lessons I take from my career so far, is that sometimes one starts thinking about one’s own ideas, and concepts that one wants to develop as an individual within one’s own head. But the reality is that science is collaborative, and there’s a joy in sharing this process. The original idea ‘in one’s own head’ is rarely the same as the one that ends up being developed through collaboration and sharing, and the intellectual input of a team. This continues to expand once your students and postdocs create their own labs, and lead their own people. It’s beautiful to be part of something that is not static and rigid, but expands and bends flexibly. It makes me feel small and big at the same time! 

You have strong teaching responsibilities. Was this something that was part of your main goals as a scientist – to be involved in teaching and outreach? 

I’ve always loved to teach/train. Education as a whole I feel is the idea of helping new generations of scientists to learn. You promote, in some way, concepts that are important for yourself as a teacher. I think there are many ways of doing this. The work I do as a group leader, mentoring PhD students and postdocs is one way of achieving this. But teaching more formally as a lecturer within the undergraduate education system is a different opportunity, and one that has given me a greater perspective of what the different research fields are. I have had to learn different aspects of cell biology, which I wasn’t so familiar with within my own research. The process of learning to teach, leads you to interact with new ideas, and discover new aspects that you previously ignored. I think teaching is a great way of learning. It challenges you, and your own students challenge you with their questions. This helps you think in a different way about all sorts of concepts. I feel I’m a much more well-rounded scientist because of this. 

Can you tell us a bit about what you have found uniquely positive about becoming a researcher in Colombia, from your education years?

I attended a bilingual school in Colombia, Colegio Bolivar. I am not sure if I can generalize my experience to the general Colombian education system, but rather something specific to the school I attended. This school tried to foster the practice of creativity, which I still carry with me. I think the practice of creativity implies being willing to be lost, and being willing to challenge yourself to enter a new field. It teaches you patience to learn a new discipline. I think in many places, in different ways, the teachers of this school taught us this philosophy, and this discipline to follow our curiosity to see where it would lead. They gave us the necessary guidelines to follow this. It taught us to lose fear, but also to not be arrogant: to realize that when you enter a new field and you do something you’ve never done before, you are not going to do it as easily or successfully as someone who has been doing this for a long time. And this is ok. This allows also you to interact with the new field in a new way, from your own perspective and your own experience. And if you strive to succeed, this leads you to develop your own strategies and your own capacities in this new field. 

Did you have many opportunities to interact with other Latin American groups, outside of Colombia?      

Not many. Within the area of parasitology, there are many labs in Latin America. From an intellectual point of view, we interact a lot in different congresses and conferences. Toxoplasmosis is a big problem in Colombia, and through our work, I have managed to meet many fantastic scientists in Colombia. Our work in Cell and Molecular Biology is different, it hasn’t allowed us to work as closely with field researchers, but I’m always excited to seek new opportunities to interact. I have lots of scientific questions, and it would be wonderful to explore these opportunities for more collaborations and interactions. 

Who are your scientific role models (both Colombian and foreign)?

When I’ve been asked this question before, I feel that my professional life has developed and has grown, taking into account many concepts and notions from so many different people. When I look at great leaders from our field I see different aspects that I would like to emulate. There are different people among my direct mentors who have had a huge influence on the work we do. David Sibley had a huge creative capacity for science, and he was capable of integrating different scientific fields in a way that I find inspiring to, and aspire to. When I worked with Arturo Zychlinsky, he too had a huge creative capacity, and he questioned concepts with new perspectives, also in a way I find inspiring. When I started working at the Whitehead Institute, Hidde Ploegh was one of my mentors, and who was never afraid of anything. He worked with toxins and radiation and any technique that was necessary to develop new methods and achieve new, previously unexplored, things in biology. Another mentor was Susan Lindquist, who is a person with a huge heart. She was capable of connecting people from different fields, and she was able to visualize the structure of scientific problems in a very unique way. And just like them, I could give you details about many different people whose abilities and qualities and skills I admire. I sometimes think to myself that I wish I could so some things in the way that such and such person does it. 

What is your favourite type of microscopy and why?

Lately, spinning disc microscopy. It’s not very difficult to work with but at the same time you can see in vivo processes in a way that is very detailed, and for very long periods of time. It’s a good combination of how accessible the technique is, and the type of scientific questions it allows you to explore. We used some spinning disc microscopes that were lent to us for the Woods Hole Physiology course in MBL which acquire simultaneous images in two channels, and give you a great temporal resolution, and a good volumetric resolution too. We have investigated our parasites with them, and it’s wonderful. 

But there are many microscopy techniques that are constantly being developed, and even when we don’t have them in the lab, or we don’t have access to them, it’s clear they will be important to explore new paradigms. I think EM continues to be one of those methods of studying biology which always leads to surprises. Sometimes you don’t imagine cells and structures and interactions looking in a specific way, and so it surprises you when you see the details that EM can provide.  

What is the most extraordinary thing you have seen by microscopy? 

Perhaps what inspired me to be a parasitologist: the observation of the quick interactions between Toxoplasma and the cells it infects. In some way, these interactions are so visible: when the parasite invades the cell, this occurs within seconds or few minutes: you don’t need to analyse a huge timelapse to see all the interactions happening between both cells. Equally, when the parasites are replicating within the host cells, and you activate them with ionophores or different perturbations and they explode out of the cell and they start moving and invading other cells, this is a truly fascinating and spectacular process to behold. It immediately leads you to ask yourself what exactly is going on at a cellular and molecular level.   

What is an important piece of advice you would give to future Colombian scientists? and especially those specializing as microscopists?

See what opportunities are available in the world, because science is a global effort. For me it has been really important to be able to move between different institutions and different countries to forge connections with different scientific groups and to learn how science is done in different places. I’ve also been able to meet extraordinary Colombian scientists, and different institutes in Colombia have a lot to contribute, especially with the unique perspective of an endemic country, where these pathogens and diseases play an important role in public health. From an ecological, epidemiological point of view, there are unique capacities and opportunities in Colombia, and finding this novel perspective is really important for scientific development. In a way, I always wondering what new notion or perspective we can contribute to the ideas we can create as a team, and to the global efforts done towards understanding the disease and the pathogen. I think that’s the most important thing for a young student: be open minded and think where these new and unique perspectives and notions exist in relation to a field of study. Foster your creative capacity from early on in your career. 

Where do you see the future of science and microscopy heading over the next decade in Colombia, and how do you hope to be part of this future? 

We work a lot in genomics and genetic manipulation. In some way, there’s been a democratization of these techniques. New methods that are now much more accessible to more scientific groups have been developed, and the cost of many genetic and genomic methods has reduced. Sequencing today, for example, is less costly than sequencing 10 years ago. The creation of, say, Oxford Nanopore, generate sequencing methods that are much cheaper than their predecessor, and they have a capacity of direct sequencing that did not exist previously. So when I think about the possibilities, when one has more limited resources, there is a lot of potential to do these types of experiments in the field, with new samples, and use biodiversity as one of the fundamental elements in research. Microscopy continues to be led by instruments that are extremely costly. When we think about cryo-EM or super-resolution microscopy, or lattice light sheet, these instruments are really expensive, and they are used in very specific fields, and they are often located in places with a purchasing power well above average. I’d love to see these instruments undergo developments that reduce the costs and increase accessibility. This is a technological problem, and I think it’s something possible to achieve, if there is a wish to create low-cost instruments. When we think about the effort that has been put into developing cell phones and cameras to make them accessible, I think we need to envisage something similar for microscopy. We need to think where we want these instruments to be used (including in field research), and who we want to give access to these technologies. I think so far, the priority of the microscopy field has been to push the frontiers of what is possible to visualize (i.e. better resolution, faster imaging, deeper imaging), and this should of course continue, but accessibility should become a priority. I’m not an engineer, so I cannot speak about the restrictions, but I think it’s possible, and important, to make state-of-the-art and vanguard microscopy accessible. Currently, by the time most institutes manage to raise the money to buy a 1 million dollar microscope, it’s outdated. It’s a lengthy process, and one that is really not even available to everyone. 

Beyond science, what do you think makes Colombia a special place? 

I think for any person, their native country has a special place in their heart. When I think about the elements that make up this magic recipe that make Colombia special, I usually think about its geography, which puts Colombia in a very special position within the American continent. It puts us right between a small link to Panama, and borders with many countries in South America. It includes coasts in the Caribbean and the Pacific. And being in such a unique geographical position results in an incredible biodiversity. We have a huge diversity of ecosystems which result in very diverse populations. There’s huge diversity in geography, biology, and sociology – among humans too, the interaction of so many different people with different customs and culture and gastronomy, all linked in one country, results in a huge potential for creativity in different disciplines. 

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