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Single Cell-Level Functional Proteomics and Genomics exemplified in Cancer and Immunology

Mark Peakman

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Medical Research Council (MRC)
We propose to create a state-of-the-art facility for single cell functional analysis, combining the latest developments in cell sorting with microfluidics-based cellomics, optical proteomics and single cell expression and genomics analysis. The expertise and methodologies brought together by the consortium create an opportunity to share technological benefits in an overlapping set of systems. The approach is innovative in being highly enabling for research across multiple clinical arenas; we will be operative in relation to multiple source materials (tissue, blood, culture) and levels of abundance. We will exploit the power of mass cytometry (CyTOF already in place) to maximize pre-sort capability, with the bonus of higher purity and data focusing. The modular design presents a challenge in terms of ensuring that platforms can be linked; but offers the considerable advantage of not being locked into a single commercial technology platform that runs the risk of scientific and budgetary constraint. The strategy thus increases our research possibilities whilst reducing the overall risk. The system will be developed in collaboration with industry, and exemplified via cohesive research programmes in immune-mediated and infectious disease, regenerative medicine and cancer. These provide distinct challenges but have significant cross-talk, making them ideal for exploring the full potential of the facility. For example, cancer growth and dissemination are characterised by immune evasion and tolerance to self/neo-antigens, whereas autoimmunity is distinguished by failure of self-antigenic tolerance, and the transfer of heterologous and autologous cells in regenerative medicine can engender responses that oppose tolerance induction. Through the synergistic development of new technology platforms that analyse complex cellular processes in cancer, inflammation, autoimmunity and alloimmunity on one site, we aim to resolve complex disease processes at the single cell level.

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