Mass spectrometry system for sensitive proteomics
Lead Research Organisation:
Queen Mary University of London
Department Name: Barts Cancer Institute
Abstract
We propose the purchase of a system for the analysis of proteins and their modifications based on a technique named liquid chromatography tandem mass spectrometry (LC-MS/MS), which is a powerful tool for proteomics (large scale and comprehensive analysis of proteins and their modifications). Proteomics technology has applications in the characterisation of mechanisms of biological processes and in the discovering of drug targets and biomarkers for diagnosis and precision medicine. LC-MS/MS is able to identify proteins in biological and clinical samples and also quantify their amounts with high precision and accuracy.
The mass spectrometry laboratory at Barts Cancer Institute (BCI) provides proteomics support to research groups at the Barts and The London School of Medicine and Dentistry (SMD) and Queen Mary University of London (QMUL). This laboratory provides a high quality proteomics service to a large community of scientists at this institution. The quality of the data derived from the laboratory is reflected in the number of high raking publications (>70 in the last 10 years) and research grants (~£15M in value) that the laboratory has supported, as well as in its non-academics outputs (eight patents and two spin-out companies).
The BCI/SMD proteomics core laboratory consists of two of LC-MS/MS systems based on mass spectrometer technology that is now more than 10 years old, and is no longer capable of fully supporting the evolving needs of its users. Particularly, the advent of new instruments with greater sensitivity and speed of analysis opens new avenues of research that our current instrumentation, due to limitations in depth and sensitivity, is not able to undertake. A recent technological development is the ability of analysing single cells, instead of an average of cells as in standard proteomics analysis. Incorporation of equipment capable of implementing this sensitive technology will allow our research community to understand tissue heterogeneity in healthy organisms and how this may contribute to disease evolution and responses to therapies.
After installation, the state-of-the-art instrument will be tested for low input and single cell proteomics projects and used by the applicants and other users of the proteomics facility in a wide range of projects that reflect BCI/SMD research strengths in cancer, vascular and endocrine biology and auto-immune disease. This new equipment will not only increase the number of projects that the BCI/SMD proteomics facility will be able to support and the quality of data for those projects, but will also allow us to perform research in single cell analysis that is not possible to undertake with our current instrumentation.
The mass spectrometry laboratory at Barts Cancer Institute (BCI) provides proteomics support to research groups at the Barts and The London School of Medicine and Dentistry (SMD) and Queen Mary University of London (QMUL). This laboratory provides a high quality proteomics service to a large community of scientists at this institution. The quality of the data derived from the laboratory is reflected in the number of high raking publications (>70 in the last 10 years) and research grants (~£15M in value) that the laboratory has supported, as well as in its non-academics outputs (eight patents and two spin-out companies).
The BCI/SMD proteomics core laboratory consists of two of LC-MS/MS systems based on mass spectrometer technology that is now more than 10 years old, and is no longer capable of fully supporting the evolving needs of its users. Particularly, the advent of new instruments with greater sensitivity and speed of analysis opens new avenues of research that our current instrumentation, due to limitations in depth and sensitivity, is not able to undertake. A recent technological development is the ability of analysing single cells, instead of an average of cells as in standard proteomics analysis. Incorporation of equipment capable of implementing this sensitive technology will allow our research community to understand tissue heterogeneity in healthy organisms and how this may contribute to disease evolution and responses to therapies.
After installation, the state-of-the-art instrument will be tested for low input and single cell proteomics projects and used by the applicants and other users of the proteomics facility in a wide range of projects that reflect BCI/SMD research strengths in cancer, vascular and endocrine biology and auto-immune disease. This new equipment will not only increase the number of projects that the BCI/SMD proteomics facility will be able to support and the quality of data for those projects, but will also allow us to perform research in single cell analysis that is not possible to undertake with our current instrumentation.
Technical Summary
We propose the purchase of a liquid chromatography tandem mass spectrometry (LC-MS/MS) system for sensitive proteomics applications, with the potential to analyse proteomes from very low input amounts (e.g. single cell level). The mass spectrometry laboratory at Barts Cancer Institute provides proteomics support to research groups at the Barts and The London School of Medicine and Dentistry (SMD) and wider Queen Mary University of London (QMUL). This is a productive laboratory with research outputs recently published in prestigious journals such as Science, Cell, Nature, Nature Biotech, among many others (>70 papers published in the last 10 years). The laboratory has also been instrumental in supporting grants relevant to MRC priorities from several funding bodies including MRC, BBSRC and UK Charities with a combined value of more than £15M, and it has delivered work that underpin eight patent families and two spin-out companies. However, its equipment (two Thermo Q-Exactive plus instruments) is based on outdated technology that is no longer state-of-the-art and is therefore not capable of supporting all the evolving needs of the facility users. Specifically, single cell and sensitive omics analyses are research areas of high demand. We propose purchasing, implementing and optimising the new system for deep proteome profiling, as well as analysis of low-input samples and single cell proteomics, phosphoproteomics, methylomics and acetylomics. The range of projects that the system will serve reflects BCI/SMD research strengths in cancer, vascular and endocrine biology and auto-immune disease. This instrument will not only increase the number of projects that the BCI/SMD proteomics facility will be able to support and the quality of data for those projects, but will also allow us to carry out research in areas such as single cell omics that is not possible to undertake with our current instrumentation.
