Cerm

Scientific research and technological innovation

Project Description

The Magnetic Resonance Research Centre (CERM) is a Centre for research, knowledge transfer, and higher education of the University of Florence, scientifically accredited at world level. The research performed comes under the umbrella of Life Sciences: proteins are produced and studied in order to understand how life functions at molecular level. The collection of nuclear magnetic resonance instruments that the CERM has at disposal make the laboratory one of the five best equipped in the world. The contribution of the Ente Cassa was decisive in the acquisition of these instruments; over the years it has provided funding of around 8,000,000 euro. The CERM is part of the European Research Infrastructure Consortium.

More specifically, in 2008 funding by the Ente Cassa enabled the acquisition of an instrument for nuclear magnetic resonance (NMR) for the structural determination of protein in the solid state. The ongoing   discovery of new drugs has made it possible in less than one century to double average life expectancy and to improve the quality of life. Pharmaceutical products are small molecules that, in almost all cases, act within the organism by bonding in a specific manner with large molecules called proteins and blocking or modifying their action.

Every organism contains several thousand different proteins and the creation of a new drug signifies identifying a specific “target” protein, and then designing and constructing in the laboratory a small molecule that is able to bond solely and exclusively with that protein. This selectivity makes it possible to avoid the drug bonding with other proteins, thus minimalizing the side effects.

Over recent years we have realised that, in order to improve our ability to design selective drugs, we need to understand what the various proteins are made of: in other words, we need to know about their structure.

In this way we can design the drug so that it can recognise these proteins and bind to them in a selective manner.

X-ray diffraction and nuclear magnetic resonance techniques make it possible to determine the structure of proteins, in crystalline form or in solution respectively. Nevertheless, a significant fraction of the pharmacological targets is made up of membrane proteins and fibrillary aggregates that do not crystallise and are insoluble so that they cannot be studied using either x-rays or NMR in solution. The membrane receptor proteins are, for instance, involved in tumours, whereas the proteins that form fibrillary aggregates are responsible for Alzheimer’s and Parkinson’s diseases.

Solid state NMR is the only technique that permits the study of these complex biological systems in conditions as close as possible to those present in vivo. The paramagnetic probes, now widely used in the NMR of proteins in solution, represent an outstanding tool for the structural characterisation of these systems.

The co-funding granted by the Ente Cassa has permitted the acquisition of the spectrometer with the highest field in existence for solid state, which has allowed CERM to set itself in the vanguard of study and structural characterisation of protein in the solid state. These studies, which have been published in leading scientific journals, have demonstrated that it is possible to resolve the structure of proteins of large dimensions and elevated pharmacological interest. The contribution of the Foundation has been decisive in improving the performance of the centre, and hence the competitiveness of the local biotechnology and pharmaceutical industries, as well as those operating in the areas of agri-foodstuffs and materials and technological innovation.

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