An interview with Hernán Grecco

What inspired you to become a scientist? 

It’s always difficult to point out a specific moment – I believe it’s more of a process. I think all the way up to the moment I entered University, I was interested in studying several very different things: History, Languages, Astrophysics – and eventually I chose Physics. Several aspects led me to this decision: I was passionate to understand the laws and rules behind the natural phenomena that one experiences; and the capacity to learn, explain, and create models, that Physics offered was unique. Another thing that had a huge impact on me was the work of Carl Sagan and other scientists/science communicators, as well as documentaries on space and astronomy. Overall, to answer your question, what led me to become a scientist was my curiosity to understand how the world works, and I found in Physics a great science that combines observations, with quantitation, modelling, and Mathematics. But my passion for other topics continued! I started studying Physics in the second half of the 1990s. I took advantage of the chance that we had at University to study other courses in parallel. I took courses on History, Philosophy, Economics. But as one progresses in one’s career, it becomes increasingly difficult to focus on other things ‘in parallel’. Moreover, I think that the fact that we didn’t have a unified campus at the University of Buenos Aires made it more difficult. For instance, the area where I studied hosted the Faculties of exact and natural sciences, as well as Architecture. But Philosophy and Languages and Engineering are at the other end of the city, and Economics is yet at another end of the city. This didn’t play in my favour with my multi-disciplinary interests. However, this meant that I found other interests within the Faculty – for instance in Chemistry and Biology. I have even done some collaboration recently, with colleagues from Industrial Design. I have always found inspiration in learning and in multidisciplinary knowledge. I think a lot of advances in each area have arisen from ‘fresh’ views, many times coming from outsiders to specific disciplines. I think if you are passionate about knowledge and the love for learning, you find excitement in multiple disciplines and areas of knowledge, rather than become restricted to one or two. And I think this is becoming easier for newer generations. I see that my students have access to YouTube and other forms of social media where they can access knowledge more easily, on various disciplines, to understand the things we now know, and how we obtained knowledge that we might now take for granted. 

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

I started my degree in Physics, like many people, due to a great interest in Astrophysics and Astronomy, and a desire to learn about the Universe. Soon, I learned that Physics can contribute to other areas of knowledge, such as Biology. I still hold some affection for Astronomy and Astrophysics, and I still read about advances in these areas out of interest and curiosity – not due to my profession. But I developed fascination for other things during my degree. I was fascinated to learn how self-generated structures emerge. How structures emerge in a biological system without any form of external plan, or external organizer. This happens at different scales: a tree, a leaf, a cell. Or even in single-cell organisms, organs, etc. All these are organized on the basis of proximity laws. So how does 3D organization emerge in a living organism? I find this incredible. I did my PhD in experimental optics, and I wanted to understand biological systems. But I understood very little of Biology, and considering what Biologists know, perhaps I still know relatively little. My PhD supervisor, Dr. Oscar Martinez was very generous, and allowed me to go and learn in a Biology lab. I went twice to the Max Planck Institute in Göttingen, to work with Thomas Jovin, whose lab was fully dedicated to Cell Biology, but with a very quantitative approach and included a lot of hardware/instrument development. My time there taught me that in Biology we need to develop the instrumentation necessary to answer many of the questions we are interested in. I think this is common in the history of Biology, Optics, and Science in general. For instance, I see in the History of Astronomy and Microscopy, or even Physics and Biology, two research areas that are constantly challenging one another to make things possible. The evolution of knowledge is based on what is possible and what is needed, and always also addressing the quantitative aspect of Biology so that it is not just description. My aim, specific to my area of research, is to find the principles behind the 3D organization of living beings.  

I finished my BSc in December 2001, a particularly difficult time for Argentina – it was the beginning of a major economic crisis – when at some point there was even a succession of about 5 presidents within a matter of days. A very unstable situation. I decided to stay in Argentina nonetheless, to do my PhD in the lab of Dr. Oscar Martinez who was doing work at the interface of experimental physics, plasmonics (the study of signals at optical frequencies along metal-dielectric interfaces at nm scales), etc. My internships in Germany allowed me to see how science was done elsewhere, and learn new things. I finished in 2007. When I finished my PhD in Argentina I decided that for my postdoc I would join a Biology lab which needed a physicist, rather than a Physics lab where I would do Biology. I went to the Max Planck Institute of Molecular Physiology in Dortmund, Germany, to the lab of Philippe Bastiaens. 

One thing that I feel is in high demand in Biology is the need for quantitative tools, data science, and modeling. I think that when I did my postdoc in a Biology lab, I started to learn how to address Biological questions. One of the most valuable things about that postdoc is that I was sitting at an office somewhere, and on the other side of my desk there was a Spanish colleague – Pedro was his name – who was a Biologist. We usually had very exciting scientific discussions, coming from different angles, and often, even with very opposite points of view. We used to discuss a lot on how to address a problem, how to solve it and so on. I remember one day we were having a very heated discussion – like only Latin people can discuss – on the phosphorylation of a protein. Some time later, our German colleagues with whom we used to share the office told me they were glad me and Pedro could solve our differences. I explained that we were just discussing about protein phosphorylation! It wasn’t a personal argument 🙂 That’s the level of passion we had. It was good for me to learn from different perspectives, and it was good for us to communicate, coming from different fields of research. It’s good to do interdisciplinary science because it even helps you to find the essence of your field and communicate it accurately. I think many good ideas come from this: from removing all the formalities/accessories and understanding what is at the heart of a scientific principle or explanation. Another thing I realized by doing science in an interdisciplinary team, is that in Science and Data Science, sometimes we do things the way they were done years or decades before – for instance before powerful computing was available. And perhaps these methods are no longer the most efficient or the most accurate anymore. Sometimes it takes a while for one to question oneself ‘why do I do things this way?’ and you realize some methods have their origin in the 1970s, when computers and other instrumentation were limited by the electronics of that time. Sometimes, until you have someone who helps you evaluate ‘why are things done this way?’ you remain trapped in your bubble of knowledge without expanding that horizon further. 

 Anyway, career-wise, I was in Philippe Bastiaens’ lab one year as a postdoc, and then I started a position as project leader – which is like a senior postdoc position where you oversee various projects – not only your own. This time allowed me to follow a research line I had already been working on as a postdoc, and I was able to incubate some new ideas that I used to develop my own lab later on. Later I stepped into a Group Leader position and started my own group also in Dortmund. These were vey exciting times, but my fully independent group was formed when I came back to Argentina. I think my lab was formed from the fusion of everything I learned and everything I acquired in the various labs I was in, in Argentina, then Göttingen, and then Dortmund. I think for setting up your own lab, interdisciplinary experience is something very valuable. And for me Microscopy is a meeting point of various disciplines and a hotspot for science – you can have Physics, Mathematics, Chemistry, Computer Science, and of course Biology. In this meeting point, we can have challenges of all disciplines: for Mathematics – how to have the best quantifier for a certain observable phenomenon; for Computation: implementing an image analysis pipeline that is highly efficient and easy to distribute. To sum it all up, there can be a wide variety of questions and challenges, and I believe the best microscopy is done when all sciences contribute to answering the questions and improving the field of imaging. In a way I feel my career is a fusion of this junction of knowledge.     

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

In Argentina you do a BSc, which is the equivalent of a BSc + MSc in other countries. In general, it is possible for Argentinians to start a PhD immediately after our BSc’s in other countries (including European countries and the USA), without the need for an MSc degree. 

I think a characteristic of education in Argentina (and not just the formal teaching/learning, but the entire process of being in a research lab and doing science) is that we have to become very resourceful and thus become independent very quickly. We have a lot less infrastructure – and this has good and bad things: on the positive side, you have to do some things from scratch and this really allows you to learn key concepts and the basics of the equipment or protocol that you do. You understand very well why things work the way they do, and why they don’t work when they don’t. You understand how a piece of equipment is designed and what its limitations are. So, when I had the chance to work with equipment in labs abroad, I noticed I understood these items better. On the other hand, it’s a disadvantage in that you have to do things from scratch (paradoxically) – this makes the entire scientific output much more complex and much slower. In the end, this is not comparable, equitable, or competitive. I feel there must be a middle ground – a balance between the two types of science, in which we are able to understand our protocols and equipment at great depth, but where we are also able to be at the crest of the wave when it comes to research, equal to the possibilities in the Global North. I don’t know what the exact balance is. I know today, it is the economic and logistical difficulties in Argentina that determine the way we do science, rather than a decision. But I think if we could find a balance, it would be ideal.   

I feel this situation I describe is not only linked to a lack of resources, but also to a lack of flow of resources and to the ecosystem. By flow of resources, I mean that sometimes the money to buy a specific equipment is there, but it does not reach the relevant ‘hands’ in a timely manner – it takes forever to reach the right hands, or the bureaucracy is too complex to be able to spend that money in a way that would be most beneficial. Some people think that spending money in science can have the same pace as other expenses of the State, and it’s not the same. It’s not the same to buy light bulbs for a building, than buying a microscope.  And by ecosystem what I mean is – when I was in Germany, all the microscopy companies were around the research institutes – all the big names of Microscopy and Optics. So, if I needed a specific objective or lens, I picked up the phone, called the company, and I had my lens or my objective the next day. This means that I was working almost without a stock of hardware. The lens I was using for each experiment was the most adequate of all, because it was thought precisely for such experiment. Moreover, this was much more affordable because I didn’t have to have stocks of lenses for the same reason. These companies didn’t just sell things to ‘me’ but also to all the academic institutes, and other industries. The big companies provided both with material, allowing science to really prosper, and this became a positive feedback loop for everyone involved. This is something that I don’t see in Latin America. Most things are imported from the USA or Europe. So if a piece from a confocal is broken, it can take months until it can be fixed. Moreover, we also have a lack of technical expertise, and by this I do not only mean the actual technical skills, but also the capacity to contact the relevant people in Japan, Europe, or elsewhere in the world, with the know-how on how to best solve a specific problem. The same is true in terms of training: in Europe you can send your trainees to get training with the people who design the equipment. We lack this possibility to some extent in Latin America, so the risk is that major pieces of equipment with a lot of potential, can be underused. I think a goal should be that those pieces of equipment in Latin America (microscopes, etc.) are used in the best possible way. 

Can you tell us a bit about your day-to-day work as a group leader and unit member heavily involved in microscopy?

Currently my group has 3 well-defined areas that have a high degree of ‘cross-talk’. Our overall aim is to understand the 3D structural organization of living organisms. For studying this, we realized we were lacking optical and computational tools to be able to answer our questions. So we design instrumentation that allows us to quantify observable phenomena and then, computational tools that allow us to put this optical information into context, and create models with biological predictive value. This is the concept of my group. It’s really interesting from several points of view. In terms of Microscopy, one of the strongest aspects of our lab is addressing the question: how can we transform “photons into molecule”? On Biological terms, this is not the final output: I want to know what is the protein concentration? What is the distribution of phosphorylated proteins? What is the activity of an enzyme? I want a Biological readout – this is what can be modeled. And then to put this in context, the greatest challenge we face is what we call in Physics, reproducibility. Each sample is unique. You can have n = 1, 2, or 100. Each cell has a different history. The concept of ‘control’ is very important in Biology, and in Physics this has a lot less importance – in a Physics syllabus we speak a lot less about controls than people do in Biology. The question is how do we compile information coming from different ‘individuals’. Something important we learned is that inter-cellular variability, which many times is a source of ‘noise’ or ‘uncertainty’ is in fact a source of information. Each individual cell is sampling a different ‘state’. If you know how to sample this and model this, you can obtain more information than if you simply average all values. For example, if I measure 100 cells and I obtain a different value say, of the amount of phosphorylated proteins in each cell, maybe this is not because I measured inaccurately, or because the cells behaved differently due to a random variable, but perhaps this is correlated with something else, and this correlation tells me something about the internal workings of the cell. This is interesting because in order to do this, I need to know that I am measuring accurately. I need to know where my error bar is coming from, if from Physics or from Biology. I find this fascinating. For this, we have invested a lot in Statistical Modelling of Biological processes. And there’s a lot of open avenues for research in this field.  

As a professor I try to encourage interactions between the different disciplines. I am in the Faculty of Exact and Natural Sciences of the University of Buenos Aires, which has various centres of Microscopy and various groups. I want to generate more meeting points for users, technicians, experts, etc. On one hand I collaborate as a member of the council of centres of microscopy. On the other hand, we have created a postgraduate degree in Microscopy, which is 1 year long and is fully hands-on. We want to train professionals and technicians to be able to work with complex microscopes. We decided to do this because what we currently have is many scientists (physicists, biologists, chemists) who might have done a PhD and used only one type of microscopy and are experts in this. But Microscopy is much more than this – it involves a range of techniques and platforms. 

Could you tell us a bit more about the graduate program you have created? 

What we want is to have professionals who can understand as many microscopes as possible, and who are best able to use the available microscopes/platforms in the region, to their highest potential. Moreover, we want people who are also able to design novel microscopes. We find it is essential to invest in human resources. We were a bit unlucky in that we wanted to start this degree at the beginning of 2019, and we couldn’t due to the COVID-19 pandemic. We find it essential that this training is mostly hands-on. So we had to wait a bit and it will only launch this year. Also, we wanted to find funding so that we can do capacity building in the region – targeted to scientists not only in Argentina, but the neighbouring countries too. We want to have small cohorts so that everyone can make the most out of the course. Moreover, if the pandemic taught us anything is the value of hybrid modalities. So we think we can combine lectures that are ‘distance learning’ with hands-on sessions in the best way possible so that many people in the region can benefit from the training. 

We aim to make it a generalist training in microscopy. It will be divided into two sections: the first will start with an introduction to Microscopy – the aim of this is to get everyone coming from different fields of expertise (Mathematics, Computer Science, Biology, Chemistry, Physics, Engineering, etc) on the same level. We will have students from a wide variety of profiles, so we want everyone to be able to understand the basics. Here we will mostly speak about resolution and contrast. The first part will be focused on the microscope. We will cover 3 areas: Optical Microscopy, Electron Microscopy, and Scanning Probe Microscopy. We will study resolution and contrast, but especially we will explore what is the process of image formation with each of these three big areas of microscopy. There will be things in common: scanning for instance, or parallelization, etc. The aim is to understand what the main components are for each set of techniques, and the role in the process of image formation of each. This first part will also have a subject targeting Image Analysis. We understand and value more and more image analysis as an individual discipline which is growing every day. We want our students to be able to use open source software, but also to be able to generate their own simple algorithms targeted to specific image analysis needs.  Then we will have a subject called Seminars – this will include seminar series, colloquiums, etc, on topics that might not necessarily be on the hands-on topics we will be teaching, but which we find essential for the students to understand, or that they know it exists. For instance, CLEM or X-ray microscopy. We think this is important because part of what we see in the scientific community is that people don’t use the most appropriate technique or tool to answer the biological question, but the one they have available. I understand this, but it would be good to expand one’s horizons: we want personnel who can best use the microscopes we have, but also that can understand, use and create the ones we want in the future. The idea would be that in the future when Argentina decides to incorporate a new type of microscope, we can send the most suitable person to get training on this, and who can come back and be the one responsible for such new piece of equipment. 

The second half of the degree will focus on the sample. We have divided this subject into two sections: Biological samples and Material science. The question will be the other way around: – instead of ‘how does a certain technique generate contrast?’, the question will be ‘given a certain biological/material science question, what are the most suitable samples to have a specific answer?’. The idea is to characterize the sample in the best way possible, with whatever single or multiple techniques necessary. Within this half of the course, we will have a subject called ‘micro-spectroscopy’ in which we will teach other complementary techniques that we think will be relevant. For instance, a flow cytometer. While someone who studied Biology likely knows this piece of equipment, someone who studied Physics likely doesn’t. The opposite is true of a spectro-fluorimeter: if you work in Engineering you probably never saw one, but if you are a Physicist you likely know what this is and how it works. We think that if you work as a Microscopist, it’s important that you know what these other related platforms do and how they work. Finally, there will be a final project, which can be done wherever the person is working, and can be relevant to the institute where he/she is working. For example, the project can be on optimizing either an imaging method or a sample preparation technique that will be valuable for the institute/projects. 

We are excited about this and look very much forward to what the future will bring. We think this will be a valuable project not just for the knowledge that will be shared, but because we hope it will promote networking in the region. People who study together for one year will likely keep in touch in the future, and can help one another. 

When I was in Germany I participated of meetings of Euro-BioImaging and I realized it goes beyond microscopy- it includes medical imaging too. One thing they said at the time, which I remember well is that they had to invest in training and career development, and incorporate this into the programs of Imaging, otherwise they would end up buying microscopes worth 1 million euros or more, and use them as magnifying glasses only. I think this is equally relevant to us in Latin America. I think we all realize that it’s worthless to have the best microscope if no one knows how to use it, or use it well. So we want to ensure that the Microscopy experts we will be training are well-paid and have career prospects. This is not just in terms of the position and ‘going up the ladder’, but also the chance to continue learning – sending our professionals to congresses, workshops and trainings so that they keep up to date. I think this can even be done in conjunction with the Microscopy companies. We might not realize this but it’s convenient for them that the person that will be responsible for the equipment is well trained. Many providers in Latin America also have this idea, and we are very glad about this. For example Zeiss was very helpful for generating this postgraduate degree.  

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

During my career I didn’t have a lot of opportunities to travel in Latin America. I don’t know if this is a good reference point because in 2001 and after, Argentina was in a situation of crisis, so this didn’t help. Moreover, I think at the time Microscopy didn’t have the level of networking that it has today. As a community we hadn’t realized the value of core facilities. And we are now trying to develop facilities that perhaps in other areas of Physics are already conventional and better established. This is only recent for Microscopy. Because we realized this value, now it’s easier to get funding too for this purpose. I think for me, participating in meetings of Euro BioImaging gave me a clear view of the direction in which Europe is steering, and realizing important points I thought were worth incorporating into our plans in Latin America. Something I’d like to highlight is that in Argentina, around 2000, despite the difficult situation we were living, there were initiatives to create for instance, the Centre for Advanced Microscopy in the University of Buenos Aires. A group of researchers from different departments bet on a project that would have common benefits. Now funding agencies prioritize this: they want to know that if you buy a piece of equipment, it will be shared, and it will benefit many groups rather than only one or two. Anyway, I feel more recently I have had a better chance to network in the region: I recently attended the LABI meeting in Montevideo, and I was recently giving a course in Chile. But I feel we still have to grow more in this direction. I think we still have room for improvement, like funding projects that promote the use of advanced microscopy as joined projects among various Latin American countries. An example of this is funding that promoted the use of the super high resolution electron microscopes that Brazil has. I think we have to scale this up for all types of microscopy. 

Have you ever faced any specific challenges as an Argentinian researcher, working abroad?

No, I don’t think I did. People were always very kind when I was in Germany. It’s difficult to talk about an entire society based on one’s experience in a research institute. The institute had over 80% of international staff so…people didn’t really have their roots in the host country. However, my German colleagues were very caring. For example, I arrived there with my family, when my son was only 8 months old. I had nothing, except for our few pieces of luggage and that’s about it. So a colleague of mine realized this and lent me toys from one of his children who were by then, older than mine. I remember also -I didn’t have a car, and my son got ill at the kindergarten. Many of my colleagues offered to drive us to pick him up and to the doctor. These kind, generous and caring attitudes were common. At the professional level, I feel the expertise and experience and way of working I brought, were valued. 

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

I think if I have to choose, it is the people I worked most closely with. My mentors. Oscar Martinez, he is a physicist. His specialty are lasers and short pulses, in fact some of the most important developments on short pulse lasers, are his. Besides of being an extraordinary scientist, he has a huge capacity of thinking outside the box. Among the two most important things I learned from him during my PhD, one of them is including PhD students in the decisions that take place in a lab – I feel this helped me a lot as a scientist. When I later joined a lab as a postdoc, I knew how to set it up, and the management process. I think some PhDs are never included in the process by their PIs: they just receive the things and get to work, so participating in the decision-making process of building a lab was unique for me. And the second thing is his extreme generosity when it came to learning new things. For instance, in my case, I wanted to learn Biology and although this was not his expertise, he agreed that I learn this, and facilitated the whole process. At the time I didn’t realize how generous he was, until I later saw other examples. I saw some labs where the PhD students were mini-clones of the PI. And I don’t feel this is ok. One hopes as a mentor that one’s trainees surpass us- that they become better scientists than us. Or at least different, so they can contribute something important and unique to science. If my trainees are my photocopies this can’t be good. They’re not a PhD, they’re my clones. Oscar’s gesture of allowing me to go to Germany, despite the fact that everything I did there is not even in my PhD thesis, was very generous. And then in Germany I worked during my PhD with Thomas Jovin – he was born in Argentina, then he went to the USA, and then to Germany. When I first met him I spoke to him in English and he replied in Spanish with a very strong ‘porteño’ accent (accent from Buenos Aires). When I visited him in Göttingen, I was very surprised. He is an MD by training – when I arrived in Göttingen and I asked for him, his assistant told me he was at the confocal. When I got there, he was changing the photomultiplier. For me this was a shock because any MD I had met until then would never have been doing some hardware work at a microscope. When I started reading his papers, I realized he was heavily involved in the development of electronics. He taught me that the ability to combine good biological questions with the capacity of developing the necessary instrumentation/hardware to answer those questions was unique and extremely valuable for both areas. He was basically doing surgery on a confocal – I don’t know many people who can per se do that 🙂 And finally, Philippe Bastiaens, who was my postdoc adviser had been a postdoc of Thomas Jovin. I wasn’t aware of this when I contacted him! I saw that he had published with Lia Pietrasanta and I asked her if she could introduce me to him. She told me he would be coming to Argentina the week after, and that she had already assigned me as his assistant. At the time, when foreign scientists came to give practical courses, they were assigned a local TA. So I had the chance to work with him during that week –  I enjoyed it very much, and I asked him if I could join his lab. With Philippe I learned a lot of things, among the most important, the capacity to know where to look for and find biological information. His lab’s strength is the quantification of biological observables, and modeling based on the process of image formation. Altogether, these 3 scientists took me on a voyage from hard core physics, biomedical sciences and molecular biology. There are other people I admire, but the 3 of them are my top. 

What is your opinion on gender balance in Argentina, given current initiatives in the country to address this important issue. How has this impacted your career? 

I think this is area-dependent. As I’ve mentioned earlier, Microscopy brings many areas of knowledge together: Physics, Mathematics, Computer Science, Biology, Chemistry, etc – and each of these areas had a very different gender balance. In Argentina there is a big gap between genders, but perhaps Biology is the discipline in which this gap is most narrow, while in Computer Science it is perhaps the widest. To give you an idea, about 25% of students entering the degree of Physics are women. The same percentage remains among the teaching assistants and research associates. This then decreases in leading roles. I think there’s a lot to do in this sense. I feel the amount and type of work we have to do varies across disciplines. I get the feeling that in Computer Science and Mathematics, we have to work a lot more even at entry level and role models (i.e. not many women are choosing these degrees in the first place), while in Biology the main work would be towards retention and career development (i.e. women are choosing this career, but they are not reaching leadership positions in the same proportions as men). Of course we have to address everything as a whole but to me it seems each discipline faces specific challenges and the emphasis is different. To me, the fact that 10% (Mathematics), or 25% (Physics) or 50% (Biology) of students choosing a specific degree are women, are indicators of different things in each case. I see that there are interesting initiatives in Argentina directly targeting different minorities, but also for instance indirect initiatives have been equally valuable, like creating kindergartens. I think an inflection point is when the family starts growing and how we consider maternity and paternity leaves, and who is responsible for childcare in the family. The creation of kindergartens allows for a different distribution of duties when it comes to childcare, which would otherwise be different without this help. I think the concept of maternity/paternity leave has been reconsidered (for the better when it comes to gender equity). For instance, when my child was born I was doing my PhD and officially, I had no legally established days for paternity leave. I was able to organize the work with my PhD advisor and stay the mornings at home. If I had been in an industry job, I would have had, at the time, 2 days of paternity leave. This of course creates inequity. I think gender dis-balance is multi-causal and we have to address these causes: role models, promoting STEM disciplines, childcare, etc. 

What is your favourite type of microscopy and why?            

That’s a difficult question. I love all of them. Besides, whenever I give a talk I always say ‘use the technique most appropriate to your research question, not the one you like the most’. But two techniques that blew my mind are light sheet microscopy -I love this method: you have time, space, multidimensionality, colour, the possibility of visualizing the full specimen, etc.  In Physics we are used to reducing dimensions. But in Biology this is difficult to do – you cannot de-contextualize a specific item, so the possibility of observing something (eg. a cell) within its full ‘context’ is extremely valuable. Linked to this, I recently started working on a technique called Fourier Ptychography optical microscopy, which I call giga-pixel imaging microscopy :). This is a technique that allows you to obtain an image with 1 Giga-pixel of information. One can acquire a 20mm diameter image, with a resolution of 1 µm. One can see a huge field of view with huge resolution. Currently, the only way to do it is with mosaic imaging. The technique I’m talking about does not mosaic imaging in the real space, but in Fourier space. This type of microscope can do this without the need for mobile parts. This allows us to study very specific types of samples, which I am very excited about. Although the principles of light sheet microscopy and Fourier plane microscopy are very different, both allow you to see a sample within its context. 

What is the most extraordinary thing you have seen by microscopy? An eureka moment for you?

It’s hard to choose one. I will say something very nerdy. There is a paper in Nature Methods, in which we were trying to show a method to quantify protein phosphorylation: https://pubmed.ncbi.nlm.nih.gov/20453867/. One of the reviewers asked a question which in my view was unnecessary, which we needed to address. One of the authors of the paper, Jian Hou, is a person who can pipette with super-human precision. The experiment we decided to do was to use control titrated samples with different levels of phosphorylation and quantify this using a biochemical technique and in parallel, quantify them with the microscopy technique we had developed. So we would have 3 measurements: we knew how much of phosphorylated and un-phorphorylated protein we had in each tube (we had tubes with 10% of phosphorylated sample, 20%, 50%,… 100%), then we had what we had quantified with the chemical tool, and then what we quantified with the microscopy tool. So, we performed the measurements, and we acquired a one to one correlation of the measurements: a straight line! This was super exciting. It’s not even an image of something recognizable, but it’s an eureka moment because it meant that we knew that our methods of measurement had a high degree of precision. Later on we realized that our microscopy method was even more sensitive than the biochemical method 🙂 this was also great. 

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

My main advice would be to spend a lot of time at the microscope without a specific purpose. What I see sometimes happening with students and researchers is that they have a biological question and the very first day they go to the microscope, they want to get a result out of it. I get that this is important in science, but imaging (and learning) is a process. One has to dedicate a lot of time to determine what is the best way to measure something: you take control samples, you ask yourself new questions, adjust parameters at the microscope, measure things using different methods, ask yourself ‘what if?’ eg. what if you expected something and you are seeing something else? Basically, understand the limitations of the sample and of the microscope. I think it’s similar to football players. Some of them are ‘always’ playing with a football – they kick it around, throw it to their heads, bump it a few times, and so on, no matter what else they are doing or the time of day it is. And then there are people who only touch the football when they practice in the field. Of course the former have a complete dominion over the football – they do with it whatever they want, while the latter are more limited. The same is true for microscopists. Someone very experienced will look at a microscopy image and notice all sorts of things. This is not because one is a wizard, but because you might have seen something similar elsewhere. You get to identify problems: if the laser intensity is too low or too high, and so on. Take enough time to use controls, rather than try to finish a paper in your first session at the microscope. My second piece of advice is that you talk to people who work on other microscopy tools, even if they have nothing to do with what you are doing. There’s a lot of things common among microscopy methods, ways of generating scientific questions, etc – and you can always learn from others. Don’t become limited by your small micro-domain of knowledge. Take advantage of the possibility of exchanging knowledge with others.

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

I think microscopy is tending towards a convergence of many techniques that will allow us to traverse multiple scales and domains of knowledge. CLEM is the tip of the iceberg, for example. Now one can freeze samples and study dynamic and static events. We now have the capacity to do multiple labeling on the same sample to generate impressive atlases linking structure, function, gene expression etc. Then there is the area of sensor development which will allow us to study things that currently we cannot see. This is in technical terms. 

In organizational terms, we have to take advantage of the renewed interest towards facilities. This has two reasons: one is the cost of equipment – commercial equipment is very expensive, and it would be great to be able to share them. The other reason is hyper-specialization of equipment – this requires trained personnel. At the same time, we still have to fund the development of small equipment. It’s great that a Physics student can use the most novel super-resolution microscope, but it’s also great that he/she can build an equipment for a specific project, so he/she can learn the basics for microscope design and can later build targeted microscopes. Otherwise if we rely solely on commercial equipment, we will lose an entire generation of specialists who can create microscopes. I think there’s a lot of interest to do this in the region. In this direction I am trying to establish links with colleagues from Industrial Design – with a project called ‘Cruza’ (https://nexciencia.exactas.uba.ar/novedoso-diseno-microscopio-desarrollado-estudinates-fisica-diseno-industrial-exactas-arquitectura-hernan-grecco), where students from Physics labs 6 and 7 (in the last year of the BSc degree and their final project), as well as students from Industrial Design collaborated together.  The idea was to transform a prototype of a microscope into a microscope that can be used by multiple labs. The aim is to teach students to work in an interdisciplinary team and goes in the direction of democratizing science. 

Beyond science, what do you think makes Argentina a special place to visit and go to as a scientist? 

It’s difficult to be objective in this question. After all this is the place where I decided to live, to develop my career, and to come back and establish my lab here. Argentina as a whole, hosts a lot of cultural and natural wealth of many different types. Despite the distances – Argentina is a huge country – you have a chance to learn from a huge amount of ways of thinking amongst the Argentinian people. There’s a lot of cultures converging, and the same goes for cuisine. We also have beautiful landscapes – you can spend weeks on end without seeing anyone else, in the middle of the forest or the desert, or the mountain, or the coast. It’s a super attractive place. In Argentina, you can easily find the ‘corner’ of the country where you belong  🙂

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