Biophysical Society Bulletin | January 2025

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Alberto Diaspro Areas of Research Nanoscale biophysics using fluorescence and label-free opti cal microscopy and spectroscopy at molecular level

Institution University of Genoa and Italian Institute of Technology

At-a-Glance

Alberto “Alby” Diaspro became enamored with examining things through a different lens as a young child after he saw an image of a snowflake crystal and was overtaken by curiosity. He was given a microscope by his grandfather and it opened up the world for him, as he could now see things oth ers overlooked. This spark has only grown as he has dedicated his career to nanoscale biophysics.

Alberto Diaspro

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, in1973 and continued living with him until he finished his doctoral degree in Electronic Engi neering 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 curi ous 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 neuro degenerative diseases. “Today I consider this to be part of the field of nanoscale biophysics, the same name as the Biophys ical 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 mar ried, 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 activi ties 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 microsco py, atomic force microscopy, differential scanning calorimetry, optical tunneling, and single-molecule imaging. I developed original two-photon excitation and super-resolved micros copy approaches for different biological questions. In 1991, after reading a paper by Hopfield, I decided to use an associa tive memory approach to classify chromatin patterns.” Now, Diaspro is a full professor of applied physics at Universi ty 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-re solved 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 orga nization 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

January 2025

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