PhD project 3
Structural analysis of protein-drug interactions by innovative Mass Spectrometry-based approaches
Protein-drug interactions are an essential starting point for potential therapeutic strategies in the field of drug discovery. The early stages of drug discovery rely heavily on advances in analytical techniques to investigate protein-protein and protein-drug interactions. This PhD project aims to develop novel, native mass spectrometry-based methodologies to probe and characterize protein interactions and protein aggregation (for example in relation to neurodegenerative diseases). Mass spectrometry will be combined with native-SEC, ion mobility spectrometry, UV photodissociation, and IR action spectroscopy to find and understand how potential small molecule drugs interact with these proteins and protein aggregates. To improve our understanding of protein interactions, advanced activation and unfolding studies will be performed in collaboration with the team in Lyon (Fr). Moreover, this project includes additional secondments within the SPIDocs consortium focusing on complementary photofragmentation methods using soft X-rays (DESY, Hamburg) and using IR and UV combined with an FTICR mass spectrometer (IMIC, Prague).
PhD project 9
Mass Spectrometry instrumentation dedicated to the studies of viral protein complexes and particles
A wide array of novel mass spectrometry technology including ion source optics for efficient desolvation of large ions, a compact ion mobility device, a digital quadrupole and ion trap, and a compact time-of-flight mass spectrometer have been developed among the members of the SPIDocs consortium. The aim of this PhD project is to use this MS-technology to design, optimise and integrate these elements into a single mass spectrometer aiming to study large biomolecular species such as intact proteins and protein complexes. This process will encompass ion optics simulations, CAD modelling, building, and benchmarking both the individual components and full mass spectrometer via well characterised protein standards. Within this project, your home-location will be MS Vision and you will graduate at the VU Amsterdam. This project also includes secondments within the SPIDocs consortium to provide expertise in ion optics simulations and instrument design (Fasmatech), digital quadrupole ion traps (University of Greifswald), applied ion mobility and CDMS (University of Manchester), and IR and UV action spectroscopy (VU Amsterdam).
PhD project 10
Application of novel Mass Spectrometry technologies for the studies of virus particles
An array of novel mass spectrometry technologies has been developed by the members of the SPIDocs consortium, which were aimed at large biomolecular species such as intact virus capsids. Virus capsids, with typical masses > 1 MDa, are challenging to measure using conventional mass spectrometry techniques. These challenges include efficient desolvation, preservation of native structures, determination of molecular weight, capsid stoichiometry and different proteoforms, and determination of their three-dimensional structure. The aim of this PhD project is to establish how these challenges can be addressed using the technology developed within the SPIDocs consortium. This includes methods such as charge reduction after ionisation, ion mobility separation and selection, and detection with a compact, high-resolution time-of-flight mass spectrometer. The performance of the new technology will be compared with established MS instrumentation, such as a variety of CE- and HPLC-based (ion mobility) mass spectrometers at VU Amsterdam, and its application to real analytical challenges in virus mass spectrometry will be evaluated at the CSSB in Hamburg. This project includes additional secondments within the SPIDocs consortium to provide expertise in protein conformation (Uppsala University), protein sample handling and measurements (VU Amsterdam) and applied ion mobility and CDMS (University of Manchester).
