PhD project 8
Native mass spectrometry with advanced fragmentation schemes for protein structural characterization
Native mass spectrometry (MS) is a powerful technique guiding biopharmaceutical research and structural biology. Control of structural conservation and deep characterization of gas-phase non-covalent protein complexes is crucial in native MS, but often hampered by the availability of only one or two dissociation techniques at most MS instruments. This PhD project aims first to develop advanced multimodal experimental schemes for top-down analysis of non-covalent protein complexes and second to study the conservation of protein structure in the gas phase during native MS experiments. A state-of-the-art 15-Tesla Fourier-transform ion cyclotron resonance mass spectrometer will be used in the project. This instrument employs multiple collision- and electron-based dissociation techniques while it is also custom-coupled to infrared and ultraviolet lasers for photodissociation experiments. Gas-phase protein fragmentation behaviour will be correlated with solution-based structural techniques such as hydrogen/deuterium exchange MS and, in collaboration with the Uppsala group, with molecular dynamics simulations. The candidate will also be seconded to other SPIDocs partners to learn protein production (European XFEL, Hamburg), computational simulations (UU, Uppsala) and be involved in photodissociation experiments with other consortium PhD candidates performed in Prague (UCBL, Lyon; UU, Uppsala and VUA, Amsterdam).
