Antonio Alcaraz grew up in Castellόn, Spain, a small city by the Mediterranean Sea, and is now a professor at the city’s Universitat Jaume I. “I am fascinated by biophysics,” he shares, “because of the enormous diversity of physical problems that it involves both from the theoretical and experimental point of view. Trying to understand the function of membrane proteins involves knowledge of fluid mechanics, electrostatics, thermodynamics, statistical physics, electronics, electrochemistry, physical chemistry, etc., while all this happens on a spatial scale in which traditional continuum theoretical models are challenged by the molecular nature of matter and it is necessary to use molecular simulation tools.”
Alcaraz, full professor in the Department of Physics at Universitat Jaume I (UJI) in Castellόn, Spain, grew up in the same city. “Castellόn is a small city located in the east of the Iberian Peninsula, by the Mediterranean Sea. It is a beautiful place because the mountains are very close to the sea and one can find different landscapes in short distances. Also important, the weather is not extreme in either summer or winter,” he says. “Although Castellón lacks some of the advantages of large cities, the place is quiet and relatively well connected to Valencia, Barcelona, and Madrid.” No one in his family was involved in science but his father, a lawyer, and mother, who did administrative work in the Police Traffic Department, instilled in Alcaraz and his sisters a love of reading, studying, and enjoying culture.
In high school, he was interested in science, English language, history, economics, and philosophy. “During my last year I met some friends that were studying for a degree in physics. I was attracted by the combination of mathematical principles with physical concepts that can be probed with experiments,” Alcaraz explains. “This feeling was intensified when biophysics came into play. Biological systems are amazing in terms of diversity and complexity. Trying to explain biological functions in terms of physicochemical molecular mechanisms is an extraordinarily challenging task.”
Alcaraz attended the historical University of Valencia to study physics as an undergraduate. “Interestingly, higher education was established in the city of Valencia in the 13th century thanks to King James I of Aragon. However, it was not until October 30, 1499 that the Juries of Valencia drew up the Constitutions of what would become the first University of Valencia,” he reports. His specialization was in fundamental physics (physics at or below the atomic scale), but he especially liked courses in thermodynamics and statistical physics. “I obtained a scholarship to do my doctorate degree in Transport Processes in Membranes in the Department of Thermodynamics, under the supervision of Salvador Mafe and Patricio Ramírez,” he explains. “I really enjoyed working with them. We got nice theoretical models of impedance spectroscopy in ion-exchange membranes that we confronted with experiments done at the University of the Saarland in Germany, where I stayed several months doing a research stay. We reported the results in a series of publications, and I got the PhD Research Award of the University of Valencia.”
Following the completion of his PhD program, he was hired by UJI as a teaching assistant. To obtain a tenure-track position, he was required to undertake postdoctoral research at other institutions. “First, I did a postdoctoral stay of several months at the University of Twente in the Netherlands, working on topics like those of my thesis (industrial separation processes, electrochemistry, water desalination) in the framework of a European Union Thematic Network,” he shares.
At UJI, he met Vicente Aguilella, who was working in membrane transport dealing with biological systems. “That was the first time that I heard the term ‘biological ion channels’ in relation to the use of ‘membrane pores.’ Vicente suggested to me that my background in membrane electrochemistry could be useful to learn ion channel electrophysiology in the laboratory of one of his collaborators, Sergey Bezrukov, at the National Institutes of Health (NIH). That stay, in 2001, widened my scientific perspective because I realized that biophysics was a fascinating world, both from the theoretical and experimental point of view,” he recalls. “From that time, I remember with special fondness the ‘chocolate seminars’ organized by Adrian Parsegian with extremely fruitful and passionate discussions with NIH staff and many visitors taking place. That stay of several months, and other similar ones in the following years, were like an open door to a new world and I will always be grateful to Vicente, Sergey, Adrian and all my other colleagues. The collaboration with Sergey’s group at NIH still goes on after more than 20 years.”
“Because of this collaboration, we were able to establish the Molecular Biophysics Laboratory at UJI, doing experimental techniques that we learned at the NIH that we have applied to multiple systems that can be considered soft matter and biointerfaces, such as bacterial and mitochondrial channels, viral proteins, neuropeptides, cell penetrating peptides, nanopores, nanoparticles, etc.,” Alcaraz states. “Now we collaborate with physicists but also with molecular biologists, biochemists, virologists, and many others.”
Now, as a full professor in the Department of Physics at UJI, he teaches basic physics to engineers, thermodynamics to chemists, and radio physics to medical students. “At the same time, I am principal investigator of several research projects related to molecular transport mechanisms in membranes induced by different types of proteins that can form ion channels—bacterial and mitochondrial proteins, neuropeptides, toxins, etc.,” he reports. “We do planar bilayer electrophysiology that we combine with theoretical models based on physicochemical hydrodynamics and electrostatics and also atomistic simulations. I am particularly interested in proteins of virus forming ion channels—also called viroporins—that are essential for virus progression and pathogenesis. Interestingly, we have been involved for years in the characterization of the ion channels formed by the envelope protein E of SARS-CoV1, and now we are extending this investigation to the E protein of SARS-CoV2.”
“One of the greatest satisfactions of my job is being able to work with students and observe their evolution. I believe that new ideas that challenge the established paradigms are totally necessary so that there can be progress in any field, but it is especially important in biophysics given its interdisciplinary nature. I am very grateful to all my students. They have taught me many things, forced me out of my comfort zone, and given me enthusiasm to work harder,” Alcaraz reveals. “In this sense, it is particularly meaningful when your students become your colleagues, as is the case with María Queralt-Martin, a former PhD student of mine who came back to our department after some years in the United States, also at the NIH. We have transitioned from a mentor-student relationship to colleagues who can ask each other for advice.”
Asked where he sees biophysics going in the future, Alcaraz notes, “In a way, biophysics is unpredictable, so it is hard to say what challenges we will face. The COVID-19 pandemic is a good example of this. We should be adaptable to give an adequate response to the challenges of each moment, but at the same time maintain sufficient basic knowledge to face future problems that we still do not know will exist.”
When he is not working, he enjoys spending time with his family, reading, and cooking, in addition to running half-marathons and biking.