A Platform for Chemical Probe Identification and Optimization Facilitating Interrogation of Biological Mechanisms

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Enabling physical sciences methods are tremendously powerful in studying proteins - the workhorses of biology. Proteins perform a significant proportion of functions in cells to make life possible and interact with one another to regulate each other's functions. In this way, proteins control the majority of cellular processes that regulate life, therefore it is crucial that we continue to develop enabling physical sciences methods to underpin the study of protein function to deliver insights that improve food security alongside tools to diagnose and treat disease. Synthetic chemical probes function by binding to protein targets and can do so either temporarily, or by linking permanently to their target. In either case, the field of "chemical proteomics" represents the approach by which interaction of a chemical probe with its protein target in cells is used to learn about the role of probe and/or protein in biology. Chemical probes can be small molecule drugs, other biologically active molecules, or tools to read-out the interactions of proteins, protein activity, or protein modifications that the cell uses to control protein function. To carry out chemical proteomics it is necessary to identify and quantify changes to proteins in the cell; this can be achieved using high-resolution mass-spectrometry. Mass-spectrometry is an analytical technique that measures the mass-to-charge ratio of ions; it requires only low sample quantities and can unambiguously identify and quantify individual proteins from cells and identify the cellular targets of synthetic chemical probes. This strategic equipment initiative will install a new state-of-the-art mass-spectrometer at The University of Leeds making chemical proteomics possible for a large group of researchers developing chemical probes and investigating biological processes relevant to animals and plants, including cancer, dementia, cardiovascular disease and crop stress. This will generate considerable opportunities for intervening in biological processes (a) to understand healthy cells better (b) to develop new therapeutics (c) to improve food security.