Ricerc@Sapienza

This proposal aims to establish the first native mass spectrometry (MS) platform in Italy to investigate protein regulation, structure, and interactions to better understand their role in physiological and pathological settings.
Native MS is an ideal method as it allows the study of the structure and dynamics of the protein complexes as well as protein-ligand interactions. The measurements are performed in non-denaturing conditions, using solutions at physiological pH without requiring organic solvents or acidic environment. Native MS integrates well with other structural approaches (X-ray crystallography, NMR, and cryo-EM) and biophysical methods to study protein-protein interactions (PPIs) and protein-ligand interactions, such as ITC, SPR, alfa-Screen, FRET.
The Q Exactive Ultra-High Mass Range (UHMR) mass spectrometer represents the latest advancement in the field as it permits evaluation of non-covalent interactions at the highest resolution and possesses a wide mass range which allows analysis of large macromolecular complexes.
We aim to employ this instrument for different interdisciplinary projects. These include the analysis of mechanisms regulating epigenetic signalling (i.e., DNMT3A and LSD2), the examination of RNA-modifying enzymes (METTL3-14) and the investigation of novel routes to fight multi-drug resistant bacteria (LPS transport system). The Q Exactive UHMR will be employed to investigate PPIs along with interactions between protein and nucleic acids, peptides, and small molecules to inform about their influence on protein function and enzyme inhibition.
This platform, ItaliaN CEntre for NaTIVE Mass Spectrometry (INCENTIVE MS), will integrate the expertise in medicinal chemistry, biochemistry, and structural and molecular biology present in the proposing departments and will pose Sapienza at the forefront of research in Life Sciences at both national and international level.