"The motivations for studying the gaseous structures of peptides and proteins range from developing efficient methodologies for protein identification and quantification to fundamental understanding of folding processes and biomolecular architectures. Mass spectrometry allows analyzing biomolecular ions in a variety of different forms, for example, as a function of charge state, bound to their targets or in multimers following aggregation. Ion mobility-mass spectrometry is a revolutionary technique regarding the separation of complex mixtures and structural isomers and can now play an important role in the study of protein shapes and their complexes. In parallel, optical spectroscopy is also emerging as a key element in gas phase methods available for investigating biomolecular ions. In this proposal, we want to combine spectroscopic approaches with high resolution mass spectrometry and ion mobility to widen and deepen the scope of mass spectrometry in its various fields of applications including structural biology, protein identification and quantification. The general idea behind our approach is to simultaneously obtain “orthogonal” information on gas phase molecular conformation from ion mobility and optical spectroscopy, with in addition the possibility of using light to induce conformational changes or the formation of new species. A goal of this cross-disciplinary proposal is to study the structural reorganization of proteins occurring in relation to aggregation, radical formation and oxidation, focusing on misfolding and the earliest stages of tau protein assembly. Moreover, fundamental understanding of structure and reactivity of peptides and proteins will serve as a lever for the development of applications in analytical sciences using photon based dissociation. Major advances are expected from pioneering instrument development and from crossing boundaries between physics, chemistry and biology."