Alberto “Alby” Diaspro was born in Genoa, Italy, but spent most of his early years in Verona. He recalls that when he was around 4 years old a girl he knew showed him a picture of a snowflake crystal. He only knew snow to be a white blanket covering the landscape and couldn’t conceive of a snowflake as a delicate crystal. “I talked about this with my grandfather Mario,” he remembers, “confessing my desire and curiosity to see the snow in the very same way. After two days I received from my grandfather an optical microscope and I was able to see the snowflakes. Now I could see things that others could not see.”
He lived with his parents, a mechanic and homemaker, until their divorce when he was 14 years old. He moved in with his grandfather, Nonno Mario, in 1973 and continued living with him until he finished his doctoral degree in Electronic Engineering 10 years later at the University of Genoa. “He bought me my first oscilloscope and my stereo that I still have and use,” Diaspro remembers. “My Trio Kenwood oscilloscope is the starting point for PhD students and postdocs when they first come to work in my lab.”
“My grandmother Anna was a beautiful woman. I was a curious and lively child like all my peers. When she died of cancer, an impossible promise rose from my heart and I whispered to her, ‘I’ll understand why, Grandma dear, so you won’t die anymore.’” While at the time it was an ambitious promise, his scientific interests do lie in the study of the complicated and delicate relationship between structure and function when considering chromatin DNA, molecular oncology, and neurodegenerative diseases. “Today I consider this to be part of the field of nanoscale biophysics, the same name as the Biophysical Society Subgroup I founded in 2010,” he explains. “The Subgroup is now renamed Nanoscale Approaches to Biology.”
In 1975, Diaspro met Teresa, and in March 1984 they married, welcoming their daughter Claudia later that year. He had recently finished his doctoral degree in electronic engineering, then called the Laurea Doctoral Degree (PhD programs began in Italy in 1984), at the University of Genoa, with a thesis on digital phase contrast and holography.
His postdoctoral work dealt with optical imaging, within a joint project of the National Institute of Cancer Research and the University of Genoa. “I was mainly involved in image processing and analysis since the optical microscope was a conventional one that I used for 3D optical sectioning. From my side optical images were 2D Fourier transform maps, and the papers that attracted and influenced my research activities were by Agard and Sedat on application of computational optical sectioning, and by Maestre, Bustamante, and Tinoco about circular intensity differential scattering,” he details. “In both cases the focus was on chromatin organization in the cell nucleus and its relationship with function. I focused on different approaches including scanning tunneling microscopy, atomic force microscopy, differential scanning calorimetry, optical tunneling, and single-molecule imaging. I developed original two-photon excitation and super-resolved microscopy approaches for different biological questions. In 1991, after reading a paper by Hopfield, I decided to use an associative memory approach to classify chromatin patterns.”
Now, Diaspro is a full professor of applied physics at University of Genoa and Research Director of the Nanoscopy research line at the Italian Institute of Technology. “I am focused on multimodal molecular optical microscopy boosted by AI. With my group, we are involved in fluorescence super-resolved microscopy, including the recent MINFLUX approach that demonstrated Angstrom-level localization precision. Starting from this point, I aim to integrate multimodal data with label-free spatial maps (phase contrast, Mueller matrix elements),” Diaspro explains. “Considering chromatin organization in the cell nucleus I have two targets, namely: 1) transforming label-free images into fluorescence molecular content ones, and 2) producing a “liquitopy” image based on multimodal data sets. Changes of chromatin organization at the interphase related to cellular function is the biophysical side of my research.”
One of the biggest challenges in his career has been discovering more about how to fight cancer, as he promised his grandmother he would. He views the identification of aloe-emodin as a new type of anti-cancer agent by means of two-photon excitation microscopy and spectroscopy as his most important research, both scientifically speaking and as a human being.
“Another challenge, today relevant for immunotherapy against solid tumors, was related to the understanding of the role of RAB5A and RAC in membrane fluidity using 2PE spatially confined photoactivations. Endocytic trafficking of RAC is required for the spatial restriction of signaling in cell migration.” He continues, “On the microscopy research side, the first demonstration of super-resolution in thick objects combining single-molecule imaging and light sheet microscopy, the first realization of the 2PE window of photoexcitation of photoactivatable fluorescent proteins, the original use of the very same wavelength for priming and depleting fluorescence under STED and 2PE conditions, the first paper on correlative nanoscopy using STED and AFM, the unprecedented use of liquid lenses in confocal laser scanning microscopy, and the first results combining circular intensity differential scattering and fluorescence to image chromatin in the nucleus are only a few of the most important accomplishments in my career. My next challenge is the “artificial microscope,” an intelligent artificial molecular microscope combining the best I can do with an optical microscope and artificial intelligence.”
Diaspro’s hope for the future of biophysics is that it will be considered what he views it as: “the best frontier in science.” For some reason it is a kind of Cinderella in physics and life sciences. The future of biophysics lies in its ability to affirm itself as a complete discipline without considering the “sirens” provided by bioengineering or biosystems to be more attractive. Biophysics is attractive by itself in the idea of Mario Ageno: “Biophysics assumes as known starting data the general principles of physics and all the consequences that derive from them by deduction, and aims to explain, on the basis of these, the complex phenomenology of living organisms.”
“Being a member of the Society increases your chance of meeting inspiring people,” Diaspro says. “In my case, I was lucky to meet Enrico Gratton and his group many years ago; to listen to a poster presentation by Erwin Neher that had a very long queue at his poster board (after his Nobel recognition); to discuss science both before and after their Nobel Prizes with scientists and friends like Stefan Hell, Eric Betzig, and W.E. Moerner; and to meet Carlos Bustamante, Laura Finzi, George Patterson, and many other key scientists in biophysics. Being a member of BPS is something that can change your research in a positive way.”