High resolution mass spectrometer for structural biology and ‘omics.

Mass spectrometry (MS) is a core technique enabling analysis of most types of biomolecules. It enables a detailed analysis using a range of sensitive techniques vital for our understanding of cellular biology. This can extend from small molecule metabolites to macromolecular complexes. This provides vital information to address modifications to proteins which regulate cellular function (post-translational modifications), studying the structure and interaction of proteins (structural biology), and discovering/identifying novel small molecule compounds. The purpose of this proposal is to provide a high-resolution MS instrument to significantly upgrade the capability of the Exeter MS Facility. The current available equipment is obsolete, at the end of its life and does not offer the full set of capabilities that MS can offer. The proposed high-resolution liquid chromatography-mass spectrometry instrument will enable a very wide range of projects that are limited by the current capability of our MS Facility. We propose a high-resolution mass spectrometer coupled to samples/liquid chromatography systems for protein and small molecule analyses plus an automated sample preparation and delivery system for hydrogen-deuterium exchange mass spectrometry (HDX-MS). The increased resolution, sensitivity, mass accuracy and MSn capability of the equipment will introduce the following new capabilities: Protein structure studies by HDX-MS. This technique will complement the structural biology expertise at Exeter and the wider community. Identification and quantitation of proteins and their post-translational modifications. Significantly increased ability to detect and identify unknown compounds. The projects that will leverage the power of high-resolution MS cover a wide area of BBSRC-facing science in the areas of structural biology, cell biology, metabolism and chemical interactions between organisms. The research covers bacteria, algae, plants, insects, worms and mammalian cells. The instrument will catalyse advances in understanding light and magneto-sensing proteins, allostery, bacterial surface structure in relation to antibiotic targets, thermosensing proteins, membrane contact sites in cells, ribosome hibernation, stem cell biology, translational control of vitamin C biosynthesis, metabolic co-operation in bacterial communities and novel compounds involved in interactions between algae, bacteria and viruses. The instrument will significantly increase specialised MS capacity in the South-West region and aims to provide a national capability for wider use of HDX-MS, including opportunities for commercial users in the longer term. It will expand the capability of the metabolomics service which already collaborates across the UK.