High-throughput Liquid Chromatography Mass Spectrometer (LC-MS) for Discovery, Translational and Clinical Proteomic research
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The Crick (a partnership between the Medical Research Council, Cancer Research UK, the Wellcome Trust and three leading universities: University College London, Imperial College London and King's College London) is a modern medical research institute hosting 120+ research laboratories. Central to The Crick's aspiration of becoming one of the world's leading research institutes is the delivery of cutting-edge science using state-of-the- art instrumentation. To achieve this, The Crick has established centralised Scientific Technology Platforms (STPs) that house this instrumentation and are supported by staff of specific expertise. This model allows operational efficiency and institute-wide consistent standards of the highest quality. The remarkable advances in proteomic technologies over the last 20 years means that mass spectrometry is now the preferred method for in-depth characterization of the protein components of biological systems. Indeed, recent technology developments are now enabling mass spectrometry-based proteomics to emerge as an essential approach for the analysis of clinical samples. The Proteomics STP collaborates with ~60 groups at The Crick, analysing upwards of 15,000 samples per year. Projects involve both Tandem Mass Tagging (TMT) isobaric tags and label free DDA and DIA for the quantitative analysis of protein expression. The technology within the STP is also used for the discovery and characterisation of post-translational modifications. To achieve this, the Proteomics STP currently houses three ThermoScientific Orbitrap instruments and a Bruker timsTOF Pro. The Orbitrap instruments are primarily used for qualitative and quantitative analysis of CoIP and proximity based labelling experiments using TMT, while the timsTOF Pro has been heavily used for the screening of small molecule fragment libraries against reactive cysteines. Demand for access to the timsTOF is now so high, that we seek to develop the capacity for label free analysis at The Crick. This proposal is for a fast-scanning mass spectrometer capable of performing high throughput DIA analysis. The unprecedented scan speed, mass resolution, chromatographic stability and speed that this system offers will enable studies that require high sensitivity, high throughput and high performance label free peptide and protein quantification.
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