SACCHI SILVIA

Silvia Sacchi obtained a Master degree in Biological Sciences in 1997 at the University of Milan and a PhD in Evolutionary and Developmental Biology in 2003 at the University of Insubria (Varese), with the research project: “In vitro evolution of flavooxidases: a rational and irrational design approach”. Between 1994 and 2000, Silvia Sacchi deserved several research fellowships from Biosensori S.p.A, Sartorious S.p.A., the Consorzio Milano Ricerche and from the University of Insubria. Starting from 2003 she worked as a post-doc fellow at the Biotechnology and Molecular Sciences Department of the University of Insubria, in 2005 in the Laboratory of Dr. Jean-Perre Mothet (Laboratoire de Neurobiologie Cellulaire et Moléculaire, Istitute Fédératif de Neurobiologie Alfred Fessard, Gif-sur-Yvette) and again, from 2006 to 2008, at the University of Insubria (functional Post-genomics and Protein Engineering Laboratory). During those years, Silvia Sacchi gained a number of research grants, fellowships and contracts from the Consorzio Interuniversitario per le Biotecnologie (CIB), the Biotechnology and Molecular Sciences Department and from Antibioticos S.p.A.

Moreover, Silvia Sacchi has been awarded with the following prizes:
• September 2003: National Research Award for the best PhD thesis on Protein Structure and Function from the Italian Biochemical and Molecular Biology Society.
• September 2004: Young Researcher Awards 2004 from the Consorzio Interuniversitario Biotecnologie.

From 2005 she is a member of the Italian Society of Biochemistry and Molecular Biology (SIB).
From 2009 to 2017 she was a Researcher of Biochemistry (05-BIO/10), and since 2018 she has been Associate Professor of Molecular Biology (05-BIO/11), at the University of Insubria where she teaches Recombinant proteins for the course of Master's Degree in Biotechnology for the Bio-Based and Health Industry and Molecular Biology for the Bachelor's Degree Course in Biotechnology and Omic Disciplines and Conservation for the Master's Degree Course in Biology and Sustainability.

Along these years, Silvia Sacchi established different international collaborations. She published 75 papers on international peer-review journals, 6 papers on books and more than 88 symposium proceedings.
Total IF: 270; Citations: 3825; H factor: 33; H 10: 21 (Scopus, june 2025); Citations: 5032; H factor: 35; i10-index: 62 (Google Scholar, june 2025)
Supervisor or co-supervisor of 42 degree theses (Bachelor's or Master's). Supervisor or tutor of 5 doctoral theses and referee for 11 national and international PhD theses.

The scientific career of Silvia Sacchi focused on the investigation of the functional and structural properties of the FAD-dependent enzyme D-amino acid oxidase (DAAO), a model protein in enzyme biochemistry. The structure-function relationships of DAAO from different sources (namely yeast and human), has been investigated by using different methodological approaches: kinetic studies, reaction mechanism and substrate specificity studies (mainly by site directed mutagenesis), structural studies, flavin reactivity studies, investigation of the redox properties, protein stability studies and folding/unfolding studies.
The experience of Silvia Sacchi in molecular biology and protein expression has been exploited in the field of enzyme biotechnology. DAAO has been employed for the production of a prototype biosensor for the analytical determination of the D-amino acids content in food specimen. For this purpose, improved enzymatic activities have been “evolved” by using rational (and directed evolution methods: new DAAO variants which oxidise both neutral and acidic D-amino acids as well as non-natural compounds were isolated.
More recently Silvia Sacchi has been involved in the investigation of the molecular mechanism of schizophrenia. In particular she is interested in studying the modulation of glutamatergic neurotransmission through the regulation of the concentration of the gliotransmitter D-serine (which is an essential activator of the NMDA receptors) and in the understanding of its correlation to schizophrenia, but also to other pathologies of the central nervous system in which a dysfunction of these receptors is implicated. In the frame of this project Silvia Sacchi was responsible of the production and the biochemical characterization of the recombinant human DAAO as well as for the investigation of the interaction with its physiological partner pLG72 both in vitro and in vivo. She studied the in vivo distribution of both the proteins and their cellular and sub-cellular localization.
Moreover, she is currently committed to the investigation of the mechanisms and factors involved in the regulation of DAAO-pLG72 interaction and of the cellular processes implicated in the degradation of the two proteins, with the purpose to unravel their role in the modulation of D-serine metabolism.
She then broadened her interests into neurochemistry and neuroscience. Currently Silvia Sacchi is studying the molecular mechanisms that in the brain are involved in the regulation of the catabolism of the neuromodulators D-serine and D-aspartate, which act respectively as coagonist and alternative agonist of N-methyl-D-aspartate (NMDAr) receptors. Alterations in the metabolism of these molecules affect NMDAr functionality and are implicated in several pathologies of the central nervous system, including schizophrenia, Alzheimer's disease and ALS. More recently she has been involved in a project aimed to studye the biosynthesis of L-serine, precursor of D-serine. In humans, L-serine is specifically produced in astrocytes through the reactions catalyzed by the enzymes 3-phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase (PSP). Silvia Sacchi has contributed in unravelling that the 3 enzymes can interact forming a functional unit, "the serinosome". She has currently begun to investigate the putative cellular signals that mediate the enzymes assembly and disassembly, concomitantly regulating their activity.
The experience acquired allows her to combine in her studies a purely biochemical approach (in vitro experiments conducted on recombinant proteins) with a cellular one (through investigations carried out in model cellular systems), applying different investigation techniques.