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The Institute of Functional Genomics (IGF) is a multidisciplinary research centre which is developing a project focused on the functional genomics of physiological and pathological cellular communications in the fields of neurobiology, endocrinology, oncology and cardiology.
This project is based on a multi-scale strategy from 'molecule to systems' and combines structural, biochemical, genetic, epigenetic, omics, physiological and behavioural studies. A major effort is paid to the development of single-cell studies through multiple dimensions and multi-omic approaches, that are necessary to address the complexity of life.
The project of IGF is increasingly based on translational research, promoted by the recruitment of teams of clinicians from different fields (neurovascular, diabetology, neuro-oncology and psychiatry). The objective is to identify new mechanisms and concepts in the field of cellular communications, in order to develop new therapeutic strategies and diagnostic tools.
MASS SPECTROMETRY FOR BIOPHYSICS: ASSEMBLY AND INTERACTIONS IN UNUSUAL DNA STRUCTURES
Valérie GABELICA
ARNA Laboratory (INSERM, CNRS & Université de Bordeaux), Institut Européen de Chimie et Biologie (IECB), Pessac, France
Our team focuses on the measurement sciences and in particular, mass spectrometry, applied to study non-covalent interactions. Nucleic acids (and more recently, foldamers and protein therapeutics) are both our model systems1 and systems on which we learn new things. In the past years, we mainly studied G-quadruplex interactions with cations and ligands. By integrating mass spectrometry in the panel of biophysical methods, we have the advantage of a direct readout of the stoichiometry the complexes, and thus the ability to reveal unexpected ones. Recently we monitored the thermal denaturation of ligand-nucleic acid complexes by mass spectrometry.2 We revealed unexpected intermediate states, and characterized their thermodynamic parameters. Our results revisit years or biophysical research based on thermal denaturation. We also focus on developing new methods (from new hardware to novel concepts for data interpretation) to obtain additional structural information on each stoichiometry separated by mass spectrometry. These advanced methods coupled to MS are ion mobility spectrometry3 and ion spectroscopy. 1) Porrini M, Rosu F, Rabin C, Darré L, Gómez H, Orozco M, Gabelica V, Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry, ACS Cent. Sci. (2017) 3(5):454-461. 2) Marchand A, Rosu F, Zenobi R, Gabelica V, Thermal Denaturation of DNA G-Quadruplexes and their Complexes with Ligands: Thermodynamic Analysis of the Multiple States Revealed by Native Mass Spectrometry, J. Am. Chem. Soc. (2018), in press. DOI: 10.1021/jacs.8b07302. 3) Gabelica V, Marklund E. Fundamentals of ion mobility spectrometry, Curr. Opin. Chem. Biol. (2018) 42:51-59.
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