Scientific career
Throughout my career I have focused on developing a versatile and adaptable profile in the field of biotechnology.
I have developed my scientific career in different countries, going through several research groups and participating in projects with very different objectives, but my priority has always been, and still is, to have fun and enjoy what I do. I always try to spend my time doing what I like to do, and like almost everyone, what I dedicate most of my time is to work. Therefore, I have no choice but to make my work something that I enjoy and motivates me every day so as not to turn life into a hell. Therefore, the skills I have developed during my scientific career have been focused on doing what I enjoy and what attracts me the most at any given moment.
Here I tell you about the set of technical skills and areas of knowledge that define me as a scientific researcher, and that in an almost intuitive way, depending on what attracted me the most, I have been developing. Over time, I have analyzed and discovered which are the most fundamental aspects of what I enjoy doing, what motivates me, and what, in the end, defines me as a professional and scientist. The aspects I am talking about are: (i) learning and being creative, (ii) team working and (iii) developing ideas that somehow contribute to society. These are the foundations on which I have built my professional career, focused on the study of biology and biotechnology.
The source of my motivation
To explain the decisions and paths that have led me to develop my professional profile, let's start from the premise that my main field of interest, to which I dedicate my career, is the study of biology and its possible applications through biotechnology. To give you an idea of how exciting biology is, keep in mind that thanks to the discoveries of Charles Darwin in the nineteenth century, today we know how evolution works. That is, basically, knowing where we come from and why we are here. So, knowing about biology is to know about the phenomena that explain what is life, it changes your perspective. The less cool side is that when you have that information you may end up thinking that you are the closest thing to a bug, with all the bad and the good that goes with it.
On the other hand, biotechnology may comfort you. Human critters, in addition to being intelligent enough to assume their condition, have the potential to creatively apply everything we know to improve society. When we apply knowledge in biology by using the capabilities of living beings for our interests we are doing biotechnology. In my opinion, biotechnology is something very, very old. I would say that the passage from the Paleolithic to the Neolithic was mainly thanks to biotechnology, even before mastering agricultural cultivation some biotechnology was already done... For instance, is the domestication of the wolf biotechnology? For me it is. For me biotechnology itself is the fact of domestication, in the sense that we take control, consciously, of some capabilities of living organisms for our benefit. But unlike what we know as traditional domestication, such as the domestication of the wolf or the elephant, or the asparagus, today with the new tools and knowledge in biology, biotechnology has acquired a dizzying potential. Today we can domesticate our own immune cells to treat cancer (CAR-T therapy) or to increase the production of goods of interest in transgenic cells (see below how my work has contributed to this).
Today, at the dawn of the 21st century, and at the doors of a new revolution, at least an industrial one, thanks to biotechnology we can consider being the masters of our evolutionary destiny. We can move from chance, necessity and the evolutive tinkering proposed by Jacques Monod or François Jacob, to the precision, design and molecular architecture of CRISPR technology or artificial intelligence. There are still barriers, but we will most likely see them overcome in the coming decades, and although we will encounter new obstacles, the incipient advances will change everything.
In addition to the motivation that, as you may have noticed, the study of biology and biotechnology gives me, as I said, one of the main factors that determine my "professional happiness" is to be able to learn continuously. For this, the study of biology and biotechnology is an ideal field, since they are fields of knowledge that rely on multiple disciplines. During the last century, biology has gone from being the little sister of the natural sciences to displaying all its complexity. For its study, different disciplines and approaches, both experimental and theoretical, overlap. Biology and biotechnology involve physics, chemistry, mathematics, engineering, computer science, etc. For example, in my case as a biologist focused on systems biology and biotechnology, it is essential to be continuously learning to expand my resources, especially in quantitative and computational aspects. This allows me to work at the interface of different disciplines and enables me to communicate with scientists from different specialties, create synergies and provide more complete answers to the problems I face. And although sometimes this can be a bit uncomfortable, because it requires working outside my comfort zone, it is very stimulating, as it not only allows me to be always learning, but also gives me a different vision, opens my mind and makes me more creative.
For me, working in teams that are rich in terms of the diversity of their members is a privilege, as it favors collective and individual performance. By interacting and pursuing common goals together with people from different backgrounds in life, cultures, ages and professional specialties, I have the opportunity to learn, to teach and to increase the value of my individual contributions due to the synergies that are generated. However, working in interdisciplinary contexts is not easy. For example, it requires an inclusive mentality and a certain humility; it is necessary to listen others and to accept other points of view that may be complementary, or even more appropriate than those that one proposes oneself. You also have to be at the team's level. This does not mean that some members are better than others; being better or worse depends on the circumstances. I mean that when you are part of a team, you depend on others as much as others depend on you, and we all have to make an equal effort, respect the common rules and be able to see the big picture while identifying the priorities of the individual role. Working in a team, especially when the team is diverse in its composition, has given me many positive experiences. Among other things, it has allowed me to build a versatile and adaptable profile, which enables me to contribute and add value in different contexts.
Looking at it from a biologist's point of view, the evolutionary point of view, it makes sense that working in a team brings out the best in you and more. Human beings are social animals. As paleoanthropologist Juan Luis Arsuaga (whom I highly recommend reading) says, an "isolated human is not a human" (I think he in turn quotes Lonrenz about chimpanzees, but this certainly applies to humans). As a summary, integrating all of the above into a paragraph, I will say that we are biology because we are animals, we are creative because we are humans and we are societies (or even cultures) because we are social. I like to think that these fundamental characteristics of our species are the foundations on which I build my career and carry out the work I am so passionate about. I work being human and my work is being human. I put biology and creativity together to contribute to society and thus take our species a little bit further. It's nothing new, we've been doing it for at least 2.5 million years.
Career path
In the technical sense, because of my interests, my studies and my research experience, I define myself as an interdisciplinary biologist who integrates experimental and computational approaches to decipher biological processes and develop biotechnological applications. From a less formal point of view, I would say that I think like a biologist who always keeps evolution in mind, I have engineering tools to measure, design and build, and I use my resources with cells like a shepherd with his sheep, who knows them and exploits them.
My career path is a bit zig-zagging, it is positively marked by the fact that before starting my university studies I worked for several years in different jobs. This experience was especially enriching, because it taught me the value of hard work, humility and tenacity to achieve goals. It also made me very sure that this was what I wanted to do when I started my studies.
In 2015 I obtained a degree in biotechnology from the Universitat de València, where almost from the beginning I worked as a collaborating student in the genetics department. During the last year of the degree I discovered the field of systems biology and I was hooked. One of the features that most caught my attention is that by using mathematical models, taking into account how the different parts that make up a biological system interact, it is possible to decipher phenomena that intuition and even direct experimental measurements cannot capture. So I decided to continue my career focusing it in the direction of systems biology, although at that time my basic knowledge in mathematical modeling was scarce.
Because of my interest in systems biology I needed to broaden my knowledge and skills in quantitative methods to do research, which would allow me to work side by side with engineers, mathematicians and physicists in the study of biological questions. So I decided to move to France, to Paris, to do a master's degree in interdisciplinary research at the Université Paris Cité (more specifically at the CRI, now called LPI). There I was able to do internships in several labs and learn new techniques, participated in the iGEM competition and started to build a network of contacts. Among those contacts was Gregory Batt, who gave me the opportunity to work in the setting up of his new systems biology lab at the Institut Pasteur in Paris (InBio).
Participating in the creation of a laboratory was a very instructive experience, I was very involved and took responsibilities for the transition of an empty space into a state-of-the-art facility for systems biology research. Once the lab was up and running, I was able to start and complete, in 2021, my PhD project as part of the team, which was composed of engineers, chemists, mathematicians, physicists and biologists. The project, which was successfully completed, aimed to maximize the production of proteins of biotechnological interest using real-time control on a yeast population so that they were maintained at optimal stress levels. In this way, we characterized the protein secretion process from the point of view of systems biology and by means of bioengineering techniques we were able to increase the production of a monoclonal antibody by 70%.
After this experience, tremendously rewarding for me, I have consolidated my profile as a systems biologist able to work at the interface of biology and engineering. Throughout my career I have contributed to scientific progress with my publications, participating in international events and transferring knowledge to students, colleagues, family and friends. As a highly motivated person (you may have noticed), I am always committed to contribute to society through my work. In particular, as a biotechnologist, I have a responsibility to translate scientific advances into innovations that improve people's lives, and I strive to achieve the highest level of quality in my research.
Currently I am still dedicated and passionate about systems biology research as a researcher at the Department of Biomedicine at the Universität Basel, Switzerland. More specifically in the lab lead by Mattia Zampieri, focused on systems pharmacology and biology of metabolism. I have just started and I can't tell much yet, but soon I will update this section with new experiences.
Scientific contributions
My most tangible scientific contributions are materialized in the form of scientific articles and participation in the international synthetic biology competition iGEM, which takes place in Boston, USA, every year. Here I will briefly summarize the three projects, focused on biotechnology and bioengineering, in which I consider my contribution has been most significant and which are also the most representative of my experience so far. I present them in chronological order, which coincides with the order of importance they have had for me, in the sense of instructive experience.
In this project I worked in an interdisciplinary team to develop a proof of concept based on producing synthetic enzymes that would remove red wine stains from fabrics. These enzymes are intended to replace perchloroethylene, a toxic solvent used in dry cleaning that is banned in Europe. We started by listening to the people who would use our product, conducting face-to-face interviews with hundreds of dry cleaners. This led to a plan for a realistic product, a stain-fighting enzymatic pretreatment that is compatible with existing cleaning technologies and workflows. We then created a library of potential stain-fighting enzymes. We modeled enzyme activity on the tissue surface and determined that performance could be substantially improved if the enzymes had a moderate binding affinity to the tissue itself. In this way, it improved the distribution of enzymes in the clothe to find the spot. To make this a reality, we identified short peptides with affinity for cotton, linen, wool, polyester and silk using the method known as Phage display. The resulting Fabric Binding Domains (FBD) were quantitatively characterized using a type of methodology called ELISA, to determine the peptides with optimal affinity according to our model. We developed a high-throughput assay to quantify stain removal on real fabric. We constructed new BioBricks, fusions of our most promising DBFs with our favorite enzymes. The resulting proteins were expressed, purified and characterized both in vitro and in situ (on real fabric with stains).
This project was realized thanks to the generous support of the Bettencourt Schueller Foundation and the Centre de Recherches Interdisciplinaries (CRI). During its realization we contributed to the InterLaboratory study project whose aim is to validate a method to measure fluorescence in absolute units. Finally, we traveled to Boston to participate in the final competition and this project obtained several nominations for best project in different categories and finally won the gold medal and the best integrated practices award.
You can find all the information about this project by clicking on the image below, and if you still want to know more you can contact me.
In this project I worked side by side with François Bertaux, engineer in the InBio team (Institut Pasteur in Paris) at the time, who led this project and from whom I learned a lot during my PhD. The goal was to build a platform that allows to maintain, monitor and control in an automatic manner the behavior of a cell culture growing in small scale bioreactors.
Small-scale, low-cost bioreactors provide very precise control of the environmental parameters of microbial cultures over long time periods. Their use is gaining popularity to carry out studies in quantitative and synthetic biology. However, the measurement capability of current equipment is limited. In this project we developed ReacSight, a strategy to improve the use of bioreactor arrays to automate measurements and reactive control of experiments. ReacSight leverages low-cost pipetting robots for sample collection, handling and loading, and provides a flexible instrument control architecture.
In the project we exploited ReacSight's capabilities in three applications in yeast. First, we demonstrated real-time optogenetic control of gene expression. Second, we explored the impact of nutrient starvation on cell fitness and stress through competition assays. Third, we performed dynamic control of the composition of a two-strain consortium. We combined customized reactors or chi.bio with automated cytometry. To further illustrate the genericity of ReacSight, we use it to enhance pipetting-capable plate readers and perform repeated antibiotic treatments on a bacterial strain isolated in the clinical setting.
For more information you can take a look at the presentation below or you can contact me. I suggest you view the presentation in full screen.
This project was led by me as part of my PhD project, working in the InBio team, at the Institut Pasteur in Paris. The objective was to maximize the production of proteins of biotechnological interest using real-time control on a yeast population in such a way that they were maintained at optimal stress levels, while maintaining maximum secretory capacity. Optimizing the production of proteins of biotechnological interest is a challenge of great industrial and pharmaceutical importance. The secretion of these proteins by the cell greatly simplifies purification processes, since the protein can be obtained directly from the culture medium, without the need to break the cells. However, for many proteins, secretion is also the limiting step in the production process, as the secretory capacities of the cells are limited. Current solutions to increase the secretory capacity of the cell involve biological engineering techniques to the cell to facilitate protein trafficking and limit protein degradation caused by excessive stress associated with secretion. This type of approach is extremely labor-intensive, and limited in many contexts.
In this project, we propose a new strategy based on the regulation of the production demand in a dynamic way, adjusting it at each moment to the stress levels. Using a small collection of difficult to secrete proteins of interest in biotechnology, a bioreactor-based platform with automated cytometry measurements and a systematic assay to quantify secreted protein levels, we demonstrate that the optimal secretion capacity is indicated by the appearance of a subpopulation of cells that accumulate large amounts of proteins, decrease growth and face significant stress, i.e., experience a saturation of their secretion capacity. In these cells, the capacities are overwhelmed by too strong a production. Using these notions, we optimized the secretion of a monoclonal antibody, increasing its production by 70% with respect to a full demand approach, by dynamically maintaining the cell population at optimal stress levels using real-time control of the production demand.
To find more information you can take a look at the presentation below, or you can contact me.
Outlook for the future
My Grandpa, who was a wise man, used to tell me that the best professional bet for the future was to be an all-rounder, someone who knew a little bit of almost everything, who was able to see the big picture, contribute in many contexts and switch from one to another easily. I agreed with him, however, when I began to study and learn about science, I thought that the best bet for a scientist was to specialize. I thought then that my grandfather was a man of another era and another profile, and the option of being a generalist was not appropriate for a scientist. Paradoxically, today, with more experience in science, at a time when we are witnessing the first milestones of artificial intelligence, being a specialist seems risky to me, like betting everything on a single card. Now, I think again that my grandfather was right, being an all-rounder, as he said, although it is impossible in its entirety, makes you diversify the bet. I am more and more convinced that a well-trained machine will be able to do the work of almost any specialist, probably, with time, also that of the generalists...
In line with what has been said, in order to maximize my chances of success, as well as following my intuition with respect to my professional diversions, I opt, as my grandfather used to say, for the all-rounder profile, or generalist. I want to emphasize that it should not be confused with superficial, but it is related to being versatile, able to contribute in a variety of contexts and in interdisciplinary teams. Finally, to be more specific, my professional perspectives, as of today, are focused on further developing this generalist profile by reinforcing my skills in data analysis, in the so-called omics approaches, in the artificial intelligence, and in developing a network of contacts to establish collaborations and face new scientific problems.