From super-resolution observation of the human retina in-vivo to high throughput Brillouin microscopy at CLN2S

First, I will briefly present an overview of the Rome’s branch of the Italian Institute of Technology (IIT), the Center for Life Nano- and Neuro Science (CLN2S), including the more recent developments and the ongoing projects. These are mostly oriented toward the development of new technological tools for biological imaging. Particularly attention will be devoted to the high throughput Brillouin (i.e. biomechanical) microscopy and to a new super-resolution microscopy technique capable of the early diagnosis of neurodegenerative diseases. The latter is a technique allowing to reach a very high spatial resolution (150 nm) with very long working distance (25 mm) objectives. This allow to look at the retinas of humans in-vivo, in a non-invasive manner, and to search for the presence of those protein aggregations that are the landmark of many neurodegenerative diseases. Our studies on the retinas of animal models (mutant mice recapitulating the Alzheimer Disease, AD) and on post-mortem AD human patients (obtained by eye- and brain-banks) shown that the same progression of the pathology takes place in the brain and in the retina, and that the observation of 200 nm sized betaAmyloid and TAU proteins aggregates would anticipate by 15/20 years the first AD symptoms. The potential applications of this instrument encompass a wide spectrum, ranging from its utilization in mass screening in the long term to serving as a fundamental tool for pharmaceutical companies seeking to expedite the evaluation of trial drugs for Alzheimer's disease therapy in the short term. As for the former, Brillouin microscopy has emerged as a non-destructive, label- and contact-free method that can probe the mechanical (viscoelastic) properties of biological samples with diffraction-limited resolution in 3D. This led to increased attention amongst the biophysical, biological, and medical research communities. After discussing the technique and its potentiality, as an example we report few examples of application in tissues, cells, and subcellular structures. Among them the investigation of the mechanical properties of the stress granules in presence of mutated FUS protein, giving insights on the critical aggregation step underlying the neurodegenerative ALS disease. Altered cellular biomechanics have been implicated as key photogenic triggers in age-related diseases. An aberrant liquid-to-solid phase transition, observed in in vitro reconstituted droplets of FUS protein, has been recently proposed as a possible pathogenic mechanism for amyotrophic lateral sclerosis (ALS). Whether such transition occurs in cell environments is currently unknown because of the limited measuring capability of the existing techniques, which are invasive or lack of subcellular resolution. The Brillouin microscopy seems to be the tool capable to solve this issue. Giancarlo Ruocco教授自2000年起担任罗马大学凝聚态物理学全职教授。他的专业领域为开发用于无序固体、玻璃及液体光谱研究的新型仪器，近年来转向生物系统成像技术。2011年起任意大利技术研究院（IIT）生命纳米与神经科学中心（CLN2S）主任及神经科学纳米技术首席研究员。他主持ERC和EIC资助项目，发表论文500余篇，被引超15000次（Scopus），H指数68（谷歌学术75）。他是乌克兰国家科学院、欧洲科学院院士。