MiniBio: Carolina Catta-Preta is currently a postdoc at Dr. David Sacks’ lab at the NIH (Bethesda, USA), where she is investigating Leishmania interactions with its insect vector, the sandfly. She started her career in Rio de Janeiro in 2007 at Carlos Chagas Filho Institute (UFRJ), in the Hertha Meyer lab under the supervision of Dr. Cristina Motta. Here she specialized in the study of symbiosis in the context of trypanosomatids and began her career as a microscopist. In 2015 she joined the lab of Prof. Jeremy Mottram at the Wellcome Centre of Integrative Parasitology (née Wellcome Trust Centre for Molecular Parasitology) in Glasgow, with whose lab she later moved to the University of York. Here she focused on understanding the Leishmania kinome, using molecular biology and optical microscopy tools as the basis of her research. In 2019 she briefly returned to Brazil to work at the Medicinal Chemistry Center (CQMED), and finally in 2021 she moved to Bethesda where she is continuing her parasitology and microscopy work.
Brazil has a long-standing history of contributions to science both, in Latin America and world-wide. It is the land of scientists as renowned as Carlos Chagas and Oswaldo Cruz. It is also a country of fascinating biodiversity, attractive the whole world around. Before becoming a scientist, were you aware of this heritage? What inspired you to become a scientist?
I wasn’t completely aware of everything they had done. I was also not fully aware that our universities did such good research/science. I knew they were excellent institutions for education, but not necessarily for science. I didn’t understand how the system worked until I was already studying Biology at the University. But as a kid and as a teenager, because I am from Rio, I was aware of the Oswaldo Cruz castle, which one can see from Rio’s main avenues, Av. Brasil. My dad would tell me who was Oswaldo Cruz, and about the vaccines and medicines being produced there. I knew he was a physician, and about his role on vaccination programs and sanitary campaigns in Brazil. I also knew about Chagas disease since I was a child, because we are taught about it at school, but at that stage, I didn’t know who Carlos Chagas was, or how important he was for parasitology and public health. I just realized much later that we have very prominent Brazilian scientists.
You have a career-long involvement in microscopy and infectious diseases. What inspired you to choose this career path?
It was serendipity really. I wanted to be a physician, but I couldn’t really afford medical school. In Brazil even when education is public, it’s an expensive degree to do: it’s very long, you cannot work while you study, and the books and other material are very expensive. For my family this wasn’t a reality, so I started thinking of other related fields. In fact, I tried odontology for a while, but quickly realized this was not for me. I realized I preferred the disciplines where I learned about the functioning of the human body. So the obvious option for me was Biological Sciences – I had excellent teachers in school that inspired me to follow this path. I’ve always been very curious. I was also very interested in teaching, which I am glad I get to do often as a scientist too.
About my choice towards infectious diseases: it wasn’t an active choice – I sought Prof. Wanderley de Souza’s lab because I was actually looking for a place where I could study symbiosis. During University I had a cell biology class where we studied the theory of Lynn Margulis (on symbiosis) – I was so excited I read two of her books in a week. I really wanted to work on something in this direction – I wasn’t even sure on what exactly – neither what type of project nor what type of models one could use, but I knew I wanted to work on this topic. So I looked for an advisor, who ended up being Dr. Cristina Motta. She worked on trypanosomatids that contain a symbiotic bacteria in their cytoplasm. This was in the context of studying cell evolution and the origin of organelles. For me, I thought “what are the chances that I love this subject and someone at UFRJ works on this very topic I’m so interested in?”. I talked to her and did an internship and then my MSc and PhD on this topic in her lab. I still love this subject, and there’s where I learned all I know about microscopy. Prof. Wanderley de Souza was the leader of the overall lab and various different PIs work within this lab on different topics of cell biology, parasitology and microscopy. It was where I learned about Trypanosoma cruzi, Leishmania sp., Giardia sp., and many other parasites. I think being in this lab was a very good school to learn not just about my project but also about all the different parasites and microscopy tools.
Altogether, it was really a shock to me what I learned about neglected diseases there, since when I was younger, I wanted to go to areas in other continents where I knew many diseases were a big health burden and didn’t realize in my own country this was such a huge problem. People still suffer with many infectious diseases, some of which don’t have treatment.
Throughout your career you have belonged to various world-renowned centres of microscopy? Can you tell us a bit about how this shaped you as a microscopist?
About my microscopy career, Prof. Wanderley de Souza’s lab at the Herta Meyer Institute in Rio de Janeiro was a fantastic school. I started working on TEM: I remember working for hours in a very cold room looking at all levels of details within cells. It was a great time. I also learned here a lot about how best to prepare all sorts of samples, how to identify artefacts, how to use the microscopes and the physical principles behind each technique. I think in that lab one can get one of the best types of training as a microscopist I have seen. All the professors there, especially Kildare Miranda and Marcia Attias, want you to know perfectly well how the microscopes work and how best to treat samples. They taught us a lot. They really know what they are doing, and they are very good at it. I learned here how to coordinate my experiments, how to ask research questions, how best to answer those questions, how to write scientific papers (because writing starts very early on), producing protocols, and how to be very diligent with your data. You weren’t expected to have a Science paper from your ‘Iniciação Cientifica’ (at undergraduate level), but they do train you very well to eventually publish one. In terms of microscopy, during this time I did TEM, SEM, FIB-SEM, high pressure freezing and freeze-substitution, and most electron microscopy tools. But I felt that although I loved microscopy, it didn’t allow me to answer all the questions I had. So still during my PhD, I started focusing on molecular biology, which I learned in Dr. Sergio Schenkman’s group. My goal was, and still is, to combine both tools (molecular and microscopy-based) to answer my scientific questions.
After my PhD I contacted Prof. Jeremy Mottram who was at the time in Glasgow (UK), and wrote a project for Science without Borders – a Brazilian initiative that promotes international research for Brazilian scientists. I had one of the last fellowships from this program. During my postdoc Jeremy’s lab moved to York, and I was there in this transition. While in York I worked on a big project that focused on the Leishmania kinome. During my time in Jeremy’s lab I did a lot of confocal microscopy. I had done some before, but in this postdoc I lived at the confocal microscopy, because we were imaging all tagged mutants related to the kinome project (about 400 mutants!). York has a fantastic bioimaging facility led by Peter O’Toole – it’s very well equipped and the team there is fantastic, so it was a great experience.
Eventually I wanted to pursue a different type of research question using some of the kinases we had identified, to validate them as drug targets, so I decided to go back to Brazil, to a group with which Jeremy had collaborations with, with Ana Paula. Here I worked on T. cruzi and helped establish CRISPR-Cas9 and some cell lines for in vivo imaging- overall I worked on tool establishment for T. cruzi based on experiences I previously had on Leishmania. I then went to CQMED-UNICAMP in São Paulo to work on medicinal chemistry. At this time I didn’t do so much microscopy, because it wasn’t the focus of the project at the time.
In my current position at the NIH in the Sacks’ lab, I again am using microscopy – mainly confocal but hopefully I will be able to go back to do some electron microscopy soon!
I feel I have a range of experiences and during my career I managed to ‘build’ a toolkit that includes molecular biology and microscopy. I think in the future as an independent researcher I can connect these dots to do what I really like, which is drug target validation. I look forward to use everything I have stablished and answer interesting and important questions as for example to characterize Leishmania molecular signatures duringdevelopment in the sandfly and how we can stop transmission – that’s what I am doing now. [Jokingly] It has some advantages to work in an insectary during winter!
Anyway, I truly believe that everything that one has learned throughout one’s career, can be applied to any scientific project. This is what science is about: making your own questions and using what you have in your hands to answer that.
Did you have many opportunities to interact with other Latin American groups, outside of Brazil?
My experience is that sometimes Brazil feels a bit isolated from the rest of Latin America – perhaps it’s the language as we are the only Portuguese speakers. I personally never collaborated with other Latin Americans while I was there. But I know there are excellent groups across the continent. My supervisor did collaborate with other groups in Argentina and other neighboring countries in the context of drug tests for T. cruzi for example. Prof. Wanderley de Souza also has plenty of collaborations – since it’s such a huge centre, the lab did have lots of collaborators from around the world, including Latin America. Once I went abroad I did have more contact with Latin Americans.
Have you ever faced any specific challenges as a Brazilian researcher, working abroad?
It’s never easy to be an outsider, and it never gets easier. In Scotland I was very well received. I loved the city, the people, the lab, everything. It was also my first experience abroad, and I was very excited about everything. But I did find the accent hard to understand. But in a short time I was able to understand better. In York it was alright, until Brexit happened. I didn’t personally suffered any discrimination, but it does affect how welcome you feel. Although in academia we live in an International environment, one does have to go to the outside world and this is where I didn’t feel welcome anymore. In the USA where I am at present it’s perhaps a similar feeling – I haven’t felt any direct discrimination, but I also don’t feel welcome. Altogether, I don’t really like to be a foreigner! I must say though that one of the best things of academia is that there is a chance to work with people from all backgrounds, cultures, languages, food, holidays, everything. And you learn a lot about other cultures and about yourself.
Who are your scientific role models (both Brazilian and foreign)?
It’s a combination of people. In terms of teaching:, and really give their time to students, I’m very grateful to all the PIs at the Herta Meyer, especially Narcisa Leal da Cunha-e-Silva, Rosianne Vommaro, Marcia Attias, Thaïs Souto-Padron and my own supervisor, Cristina Motta, for making us think on how to best answer our questions. Cristina also has a postgraduate education in philosophy so she would bring up very intellectually challenging concepts and it’s something I really appreciated in my education. It wasn’t just a focus on the techniques, but also focusing on the big picture, which I really appreciated. In terms of leadership, Jeremy Mottram is a great leader. He always has his door open and he was very present. He gave me very good opportunities to collaborate with other people and in his lab is where I decided what I wanted to do. Altogether I think they all have key contributions that I admire, and for which I therefore consider them role models.
What is your favourite type of microscopy and why?
I truly love confocal microscopy because it’s so pretty and colourful J. The only thing I miss in electron microscopy is the colours. But seriously, no, as a microscopist you know how it is: every time you try a new technique, this becomes the favourite for a while. They are all great! But confocal has so many options: so many different things one can do. The sky is the limit.
What is the most extraordinary thing you have seen by microscopy? An ‘eureka’ moment for you?
Two things: one from the beginning of my career, and one from now. The first is in my PhD project: I was studying interactions between organelles and metabolic exchanges, and using TEM I could see the organelles really close to each other, and membranes fusing: it’s so perfect how the cells can regulate these types of mechanisms where membranes go very close to each other to exchange material. I was able to see with my own eyes, things I have once read in text books, especially using new techniques at the time that allowed improved resolution. It was great to know I was ‘surfing’ on the unknown.
The second moment, on which I almost cried, was seeing a Leishmania parasite infecting a sandfly midgut. This was beautiful biology to see. These are the things only microscopy can give you. Actually seeing something happening with the cells makes all the difference.
What is an important piece of advice you would give to future Brazilian scientists? and especially those specializing as microscopists?
Start early, because it’s not an easy path. But if that’s what you want (and you can change your mind if not), really apply yourself and try to master what you are proposing yourself to do. Get a good grip of the technique and the project. Study a lot and listen to people who have worked on things before you: don’t try to re-invent the wheel. It’s not that more experienced people are always right, but experience is very important. Also, collaborate as much as you can. You don’t have to know everything. You have to know a bit of everything and have a strength/expertise that you can provide and contribute to science.
Where do you see the future of microscopy heading over the next decade in Brazil, and how do you hope to be part of this future?
I see a bright future coming. Investment from recent years have resulted in good equipment, good centres, good infrastructure. There were more opportunities for the students at the time, which has led to building an excellent workforce now of excellent professionals. These professionally are now not only contributing as scientists but also as teachers, training the next generation. There’s no reason why we cannot make vanguard science, as long as there is enough money to support science in the country. Moreover, because of financial and logistic difficulties, Brazilians can be very creative: we can do a lot with very little. I am always impressed with the quality of science done in the country despite not having many resources.
Beyond that, in the last couple of years with the current administration in Brazil there were cuts of up to 90% for science and research budget. I think the world should be aware of this. And as a scientific community we should support each other better. Many countries (including Brazil) have great potential to do great science and it is a shame this is hindered by political challenges. But I am very positive we will overcome this and re-establish everything we lost in the last few years.
Finally, Brazil is the largest Latin American country, and one of the largest in the world. Beyond the science, what do you think makes Brazil a special place to visit and go to as a scientist?
As a scientist, I think a valuable part is the mentality of resilience and perseverance: we don’t take ‘no’ as an answer, ever. We find our way around the problems. I think everyone in science should learn how to do it if they don’t know it already. Also, learning how to plan your experiments: due to the logistics in the country, getting reagents takes a lot of time, so you need to plan properly. Equally, as a scientist you’d learn too how to perform high quality science at low cost. We don’t spend more than we need to spend. Personally, I think Brazil is an excellent place to visit: we are very welcoming, and we will be very keen to show you our country or at least our own region. We will want to take you everywhere sightseeing. We are really proud of our culture, cities, food and people in general, so we will want to show you this.