An interview with Nelson Barrera
Posted by Mariana De Niz, on 20 December 2022
MiniBio: Dr. Nelson Barrera is an Associate Professor at Pontificia Universidad Católica de Chile, where his group combines ‘omics’ technologies and microscopy to study various aspects of membrane protein biology, structural biology, biophysics, and biochemistry. He is also a committee member of the Advanced Microscopy Unit, as well as the Mass Spectroscopy Unit. Nelson studied for his undergraduate, MSc, and Ph.D. degrees at Pontificia Universidad Católica de Chile, where he specialized in membrane proteins. He did his Ph.D. in the lab of Dr. Manuel Villalón. During this time he undertook several internships at Universidad de Chile and Johns Hopkins, where he furthered his knowledge in electrophysiology. Later he did two postdocs at the University of Cambridge in the labs of Dr. John Michael Edwardson and Dr. Carol Robinson. He was a Visiting Professor at Oxford University and established his independent lab in Santiago de Chile, where he currently works.
What inspired you to become a scientist?
In Chile, like in many other countries, you apply to the careers you’re interested in, with a ranking or order of preference. I studied for a BSc in Biochemistry, but it was not clear in my mind at that point that this is what I wanted to study. In fact, my mother recently visited and brought some old documents. Among them was the document where I wrote down my preferences – Biochemistry was at the top, but I had other choices: 3 different fields of Engineering were my 2nd, 3rd, and 4th choices. Then I selected Physics as my 5th choice, then Biology, and then Biochemistry at another University. Clearly, I was interested in Biochemistry because it was my top choice in two different universities, but it was definitely not the only field that caught my interest. It was when I was studying for my BSc in Biochemistry that I decided I would continue in the Academic track. The University where I studied has a strong focus on research, so this was somewhat a decisive aspect for me. I discovered I truly enjoyed research. By the end of my BSc degree there was the option, at the same university, to do a MSc, and after that a Ph.D. Afterward, I continued developing an academic career by undertaking 2 postdoctoral positions.
You have a career-long involvement in membrane proteins and microscopy. Can you tell us a bit about what inspired you to choose these paths?
My love for membrane proteins began in the 3rd year of my degree. I really became fascinated by the structural biology and biochemistry of membrane proteins. In 3rd and 4th year, I studied Biochemistry and Physiology, including cellular systems. There I discovered the importance of membrane structure, ion channels, and some pathologies associated with them – through them I reached the topic of membrane proteins. By the time I started my MSc and Ph.D., it was clear to me that this was the topic I was most interested in and ultimately the topic I developed my thesis on. I’m still passionate about this 🙂 Regarding my academic path, as mentioned before, I studied for my BSc, MSc, and Ph.D. at Pontificia Universidad Católica de Chile, in Santiago. While I was doing my Ph.D. I did an internship at Universidad de Chile – also in Santiago, which is one of the top Universities when it comes to Physiology. I also did an internship at Johns Hopkins University to study electrophysiology in living systems- patch clamp, voltage clamp, and intracellular recordings, which I then incorporated into my research.
Membrane proteins are important because they are the link between two environments. These proteins can be ion channels, receptors, transporters, enzymes, etc. In the case of receptors, in particular, an agonist (or drug) is always specific to a receptor. Natural agonists tend to be specific too. In many cases though, there are direct structural interactions between receptors or between their transduction pathways, which is a phenomenon called cross-talk. Therefore, specificity is not given by a receptor and its agonist, but rather by a complex system that involves interactions between different proteins. The downstream response is therefore not specific to one receptor. This quantitative and a bit more detached area from Biology is something that attracted my attention during my Ph.D. Of course, during that time we didn’t have all the tools that we now have to study these phenomena. Structural and molecular tools were still catching up. This led me to study transduction pathways, rather than structural biology or something that required tools that we simply didn’t have. I then did two consecutive postdocs at the University of Cambridge, UK. One of them focused on Molecular Pharmacology, where I acquired my skills in atomic force microscopy. My second postdoc focused on Biological Chemistry. Here I basically learned all the mass spectrometry of ligand-protein complexes, ‘omics’ such as proteomics, lipidomics, and so on. After my postdocs, I came back to Chile as an Assistant Professor for about 1 year. Then I went to Oxford University as a Visiting Professor for around 3 months, and then I came back on a more permanent basis as a principal investigator at Pontificia Universidad Católica in Chile. Ultimately, I think I managed to join my interest in Engineering and Biochemistry via microscopy! It has allowed me to achieve more quantitative outputs than most biochemical tools allow for.
Can you tell us a bit about what you have found uniquely positive about becoming a researcher in Chile, from your education years?
By the time when I was studying, there was a very noticeable difference between the private and public schools in the elementary, junior high school, and high school systems. I studied in public schools, so I studied for free all along, funded by the state. While this poses some advantages, there’s a difference in the depth of knowledge achieved by both educational systems. I think in my generation, the proportion of people who got to study careers within the area of Science and Technology was much higher than expected. I don’t know if there’s something specific that was decisive for my career. But I do think more should be done in terms of outreach at pre-BSc levels, to reach students in public and private education systems. At the moment there’s a significant difference, leaving students in public schools at a disadvantage.
Can you tell us a bit about your day-to-day work as a group leader at the Pontificia Universidad Catolica de Chile, and as a member of the Advanced Microscopy Unit?
My lab follows various research lines. The unifying topic is membrane proteins, but we focus on areas including pharmacology, biomedicine, traditional biochemistry, and physicochemistry. This includes method development and establishment including mass spectrometry, electrophysiology, atomic force microscopy, and molecular biology. When I arrive at the lab, I discuss the results with my team, and together we plan future experiments. The idea is that we exchange ideas and give one another feedback. Since membrane proteins is, by nature, an interdisciplinary field, my team is composed of people with very different skill sets – Physics, Engineering, Statistics, Medicine, Chemistry, Biology, and Biochemistry. The supervision of a team with such diverse skills requires that we are all able to communicate in a common language that integrates all the various disciplines. It is not trivial for a group leader to direct such a diverse team, but I think I’ve managed successfully to do so.
My work at the Advanced Microscopy Unit is a different activity I carry out. We have a mixture of state-of-the-art microscopes, and some a bit more traditional. I’m a member of a committee that proposes ideas on how to expand the infrastructure and services – this includes all microscopy platforms. We are about seven people on this committee so it’s all a team effort. The Faculty of Biological Sciences, where I belong, has five service Units. One of them is Microscopy, but I’m also in the ‘Omics’ Unit. These units give service to everyone who requires it – it’s not restricted to the Pontificia Universidad Católica de Chile.
Did you have many opportunities to interact with other Latin American groups, outside of Chile?
I have worked with groups in Brazil (mostly under the umbrella of microscopy) and Argentina (mostly under the umbrella of omics). I think both collaborations have been very fruitful. In both cases, the connection arose from their side, rather than from my side. Even though this has been circumstantial, I completely support the idea of collaborating beyond the borders of one’s own country. By geography, both Argentina and Brazil are immediate neighbours to Chile and I like the idea of collaborating with countries nearby. In the USA and Europe, there are more researchers, better infrastructure, and more resources invested in science and technology, but I think collaborations should be guided by the research question. Of course, if it’s something very complex that requires equipment that’s not available in the entire region, then this justifies collaborating with other countries that do have access to these tools.
Who are your scientific role models (both Chilean and foreign)?
I think one’s previous supervisors are usually one’s role models because of the amount of time spent, the work done together, and the mentor-mentee relationship that is often established. I have been very lucky that all my supervisors were great mentors. Obviously, everyone has virtues and faults, but their qualities definitely made them my role models. I remember that I learned electrophysiology from a postdoc who was working in the same lab where I did my Ph.D. His name is Bernardo Morales – he taught me this, and I had the tools to specialize further in Johns Hopkins University and Universidad de Chile. Because of this, I didn’t start from scratch in either internship. On the other hand, when it comes to developing skills within the integrated topic of physiology, in a versatile and interdisciplinary manner, Dr. Manuel Villalón, my Ph.D. supervisor was my mentor. He taught me to see the big picture – to see the context of the research question rather than something tiny. Later, my first postdoc supervisor – Dr. John Michael Edwardson in Cambridge taught me the bases of atomic force microscopy and its application to Biology. When I learned how to do AFM, this technique was mostly used in Physics disciplines – mostly for material sciences. It was barely starting in the field of Biology, so I learned how to re-target this important tool to address biological questions. I developed this with time, and it became a huge focus of my research. In my second postdoc, my supervisor, Dr. Carol Robinson, taught me how to focus on mass spectrometry. I arrived at her lab to integrate AFM and Mass-Spec. She gave me all the freedom to do this, and the research I wanted. Because of this freedom, I was able to focus on membrane proteins, which was a newly developing topic and now is a major interest. She taught me not to be shy with my ideas, but to take risks.
What is your opinion on gender balance in Chile, given current initiatives in the country to address this important issue? How has this impacted your career?
I think we still have a disbalance in Chile. I don’t know the statistics at all levels, but at PI levels there are more men than women. Regarding my mentors, Carol, my second postdoc supervisor, she’s a Dame (one of the Royal ranks) because of her contributions to science. But she always made it clear that it wasn’t easy for her to achieve the rank of Professor (or Dame) as a woman. She was the first woman PI in the Department of Chemistry at Cambridge University and when she moved to Oxford University, she became the first woman PI in their Department of Chemistry. These are great Universities, yet she achieved this around the year 2000. That’s shocking. Despite that, she taught us that everything is possible. She took some years off to take care of her children, and “despite” this gap, she is an internationally renowned and recognized scientist in her field. Perhaps now it is becoming easier to deal with these gaps. Perhaps now there is also a better focus on work-life balance. I think that, as long as the tasks of family care are put solely on women, gender balance won’t be achieved, neither at a professional nor at a personal level. It will always be more difficult for women to reach the highest levels of power. How to promote this, I don’t know, but I think it’s something vital to address. Regarding my lab, in the first two years, my team was 100% men. After the 2nd year and possibly until now it’s almost a 50:50 ratio. I haven’t intentionally done this, but it’s something that has happened naturally, which is perhaps a good indication that at a system level, things are changing. I don’t think gender should be a limitation to studying any career you want.
Have you faced any challenges as a foreigner working abroad, outside of Chile?
I spent 6 years in the UK. My language skills weren’t the best when I arrived in Cambridge, so this was a challenge- but it improved with time. Of course, in any country, one has to adapt culturally, and in the UK I did notice a cultural difference. But I can’t say I ever felt any discrimination either. Moreover, I think Cambridge, Oxford, and London are cosmopolitan, so this helps too. Perhaps in countries or cities with a lower level of diversity or cultural mix, there might be other challenges.
What is your favourite type of microscopy and why?
Atomic Force Microscopy of course. I spent countless hours sitting at this microscope and so indeed, it’s my favourite. It’s not optical microscopy, and sometimes it’s difficult for students to understand that this is a type of microscope too. It uses physical concepts which are different from conventional optical microscopy. It has advantages and disadvantages compared to other forms of microscopy. For instance, AFM has many similarities with EM and fluorescence microscopy, including pros and cons. In papers where I’ve used this technology, AFM was used in combination with other technologies. So, I think it’s an interesting tool in the context of integrative research that joins several disciplines.
What is the most extraordinary thing you have seen by microscopy? An eureka moment for you?
I think beyond any scientific question, the eureka moment has come with the tool itself. You can use AFM to do force spectroscopy, to measure the interaction between the tip and the surface. The tip can be functionalized with drugs or ligands, proteins, polymers, etc. In AFM you use tips in a cantilever to do imaging. You need to find very precise parameters to get an image. In the air, it is relatively easy to find these parameters, but in liquid, this becomes much more complicated. There are many resonance frequencies, and you must choose one – which might or might not work. Once you find the right frequency, you can acquire the image. I find the process of achieving an image fascinating. In MassSpec, you see spectra, but the spectrum is a physical-chemical property of the molecule – either you see it or you don’t. It’s similar in AFM- either you see it or you don’t. It’s fascinating. Moreover, it’s not a trivial technique, it takes a lot of effort to reach these parameters.
What is an important piece of advice you would give to future Chilean scientists? and especially those specializing as microscopists?
First, I’d say it’s a great choice 🙂 there’s a lot to do in the field of microscopy. I would take the following approach: Microscopy is fascinating to children for example – they love what they see down the microscope. And once they see what this tool allows them to do, they can then learn the principles of how the tool works. I would suggest they should familiarize themselves with all types of microscopy and how they work. Perhaps you’ll then find one that you love more – and so try to specialize in this area. Then you have to define whether you like research and if you do, whether you like to address biological questions or methodological questions. If it’s a biological question, you should be prepared to tackle your questions with various tools. On the other hand, if you choose to become a method-developer, you should acquire a lot of expertise in the area that you like. There are scientists with very varied interests, and for instance, method-developers have also won a huge amount of Nobel Prizes – for instance for developing super-resolution microscopy. Microscopy is a huge field with lots of possibilities.
Where do you see the future of science and microscopy heading over the next decade in Chile, and how do you hope to be part of this future?
I think in Chile (as well as perhaps other Latin American countries), the task at present is to catch up with the rest of the world when it comes to developing microscopy tools. For example, we don’t have cryo-EM, but we need the resources and expertise. We need to convince the authorities that this investment is worth it and why. We have to emphasize the biomedical applications. This is what I mean by catching up, in terms of technology, knowledge, and tools.
I want to be part of this wave of scientists that will be able to specialize in new equipment and bring this know-how to Chile. I want to close this gap – because while you learn new things you also apply the knowledge you already have. Moreover, students have to take a bigger leap to close this gap and I feel many more experienced scientists represent an intermediate step in this goal, to facilitate knowledge that is already acquired, and the one that will be novel for the next generation. I hope that, in upcoming generations, young scientists can pose themselves questions that can be addressed with equipment that we have in-house in the country, not 20,000 km away. Collaborations will continue to exist, but true democratic science and true accessibility requires that you have access to specific equipment at home. It’s all a combination of students, professors, experts, investment, technology, and funding. In terms of trends, it’s been difficult to find human resources in Chile – namely, Ph.D. students and postdocs interested in pursuing the research track. In addition, I’m not sure how it is now, but there was a time when the “diaspora” (i.e. researchers from Chile working abroad) was much larger than the research force staying in the country to do research. Retention is another important thing to address. I don’t think it’s only in my area, but many labs are finding it difficult to recruit people. I think the gap in infrastructure and funding has to be closed for talent not to leave the country. If we don’t close this gap, of course, the diaspora will continue to increase. I think retention is not just something Chile has to address but rather, it’s an issue common to all Latin America.
Beyond science, what do you think makes Chile a special place to visit and go to as a scientist?
I’m from Arica, in the North of Chile which it’s a desert. In Santiago, the climate is more temperate. The South is beautiful too – perhaps I want to grow old over there. Chile has a versatile landscape, huge cultural diversity, and indigenous groups. It’s a very rich country, from the deserts in the North to the Antarctic in the South, and from the Andes mountains to the Pacific Ocean. All of that within the same country makes Chile an amazing place to visit.