The "SEISMIC" facility for Spatially rEsolved sIngle and Sub-cellular oMICs

An exciting innovation in the analysis of a biological system is sampling on a very small nanoscale using a specialised needle (nano capillary sampling). Cells are located under a specialised (confocal) microscope and cells or even small parts of cells can be sampled. This uniquely provides spatial information and can be performed on living cells which will allow scientists to understand important biological phenomenon such as how cells communicate with each other and how cells become cancerous.

Our resource which we have called SEISMIC will provide an automated platform based on nano capillary sampling. We will work with users within the UK research community to extract single cells and their sub- cellular compartments under a microscope. The extracted cellular materials can be analysed using a variety of approaches such as mass spectrometry which separates molecules by mass and charge to profile for example drugs, metabolites and lipids or apply other techniques to profile nucleic acids. This will allow an unprecedented view of cells and can be applied to a plethora of biological questions which inform us on for example the rules of life or how pathogens cause disease or how cells age, information which can be harnessed to develop new therapeutic interventions which will ultimately benefit society.

The SEISMIC resource will be available free of charge to BBSRC users for the first 36 months, either with or without downstream mass spectrometry analysis. Users will be able to perform their experiments using the facilities at Surrey, and hands on access to SEISMIC will be supported through travel grants. This facility will be the first of its kind in the UK and therefore will play a role in maintaining world leading science in the UK.

The ability to carry out "omics" analysis at the single cell level is already significantly enhancing our understanding of cellular properties and interactions. However, current approaches do not allow spatial resolution, which is critical for understanding important biology that happens at the sub-cellular level, or spatial phenomena that govern cell survival, proliferation, development, or death. We will manage the UK's first facility for spatially resolved single cell "omics", SEISMIC, to improve animal and human health.
An exciting innovation in bioanalysis is nano-capillary sampling. Cells are located under a confocal microscope and either a whole cell or sub-cellular components are aspirated into a nano-capillary and then either sprayed directly into a mass spectrometer or sampled into a 96 well plate. This uniquely provides the opportunity to sample cells under a microscope and retain morphology and positional information, a feature that is not available in other systems. This is a platform technology for single and sub-cellular extraction that can be coupled to ANY downstream "omics" measurements. We and others have already applied this technology coupled to mass spectrometry for metabolic profiling in live mammalian and plant cells and their sub-cellular compartments and is also compatible with transcriptomics, proteomics, and genomics.
The SEISMIC resource will be a free service for the first 36 months to BBSRC users. This resource will be provided flexibly, either with or without mass spectrometry "omics" analysis as informed by our community survey. Users will be able to culture their own cells using the facilities at Surrey, and we have budgeted for travel grants to enable this. It is envisaged that most downstream "omics" analysis will take place at Surrey. However our survey identified some users with an interest in carrying out downstream analysis in their own laboratories which the flexibility of the facility will easily allow.