Annual Workshop Speaker: Marino Zerial

Digital models of human liver tissue provide new insights into pathophysiological mechanisms

Marino Zerial is Director at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany.

ABSTRACT

The liver is the largest metabolic organ of the human body and vital for blood detoxification, storage of metabolites and the production of digestive compounds. Its functions depend on a complex three-dimensional (3D) tissue architecture. The functional unit of the liver is the lobule, which consists of two intertwined, 3D microcirculatory systems, the sinusoidal network that allows blood flow in the liver tissue and the bile canalicular network that secretes and transports the bile necessary for food digestion. We aim to understand how such a complex tissue organization emerges from the coordinated interactions between components at multi-scale, from molecules to cell to tissue. To address this problem, we developed a pipeline of multiphoton imaging, 3D digital reconstructions and computational simulations and applied it to generate spatially resolved geometrical models of mouse and human liver tissue. These models could be exploited to generate biliary fluid dynamic models and simulations that can be applied to study alterations of liver function in human patients affected by non-alcoholic fatty liver disease (NAFLD). Spatially resolved models of human liver tissue are useful to understand the principles of cell and liver tissue organization, help the early detection of disease and gain new insights into the underlying pathogenic mechanisms.

ABOUT THE SPEAKER

Marino Zerial graduated in biology at the University of Trieste with a thesis on lysosomal storage disorders (1982). He conducted post-doctoral studies at Institut Jacques Monod (Paris) and the EMBL (Heidelberg). He then became group leader at EMBL (1989), and Max Planck Director as well as co-founder of the Max Planck Institute of Molecular Cell Biology and Genetics, MPI-CBG (Dresden, 1998). In addition, he is Honorary Professor at the Medical Faculty of the Technische Universität Dresden.

Marino Zerial has made key contributions towards the understanding of the molecular mechanisms of endocytosis. His work on Rab GTPases as master regulators of organelle biogenesis and membrane fusion has established key principles which are textbook knowledge. He has been working on various translational projects, including the role of endocytosis in bacterial infection, development of image-based high-content screenings, delivery of macromolecule therapeutics and studies of human liver diseases.

Marino Zerial was awarded several international research prizes, the 1994 FEBS Anniversary Prize, the Chiara D’Onofrio Prize (1999), and the prestigious Leibniz Prize (2006). Furthermore, he was elected EMBO Member (1996), Member of the Istituto Veneto di Scienze, Lettere ed Arti (2019), and recently International Honorary Member of the American Academy of Arts and Sciences (2021).

Marino Zerial at the MPI-CBG

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