MIB CDFA - Application of novel imaging technologies towards quantitative analytical phenotyping of single cells

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

The feasibility account will offer a step change from the limitations of present light based microscope imaging techniques to offer high resolution data to enable quantitative analysis of intracellular biological events. To achieve this goal the collaborative group from within the Manchester Interdisciplinary Biocentre will apply pioneering molecular imaging technology in parallel to enable cellular phenotyping, and detection of the intracellular localization and movement of metabolites. There are numerous areas of research within the biological/biomedical field that require the ability to quantitatively analyse single cells and large cell populations. For example, metabolomic studies have the potential to yield understanding of complex disease processes, drug toxicity and cellular function. Tools are required that enable metabolites to be identified and, more importantly, mapped spatially within a cell or tissue in-situ with minimal chemical intervention. In the field of stem cell research, cell type determination requires arduous procedures including manipulation, isolation and fixation of cells and subsequent immunohistochemistry. This proposal seeks to combine new and emerging technologies and methodologies for cellular manipulation, sorting and imaging. The account will stretch the boundaries of imaging techniques into novel cell based applications combined with micro/nano-fluidic technology through new collaborations at the interface of the physical sciences, life sciences, and medicine. This would provide enormously powerful new tools with potential applications in systems biology, fundamental cell biology, through to medical diagnostics.

Planned Impact

The suite of projects proposed will demonstrate the full capability of our enabling technologies applied to cell imaging and characterisation, and reveal unique potential for their development. If successful, these developments will be significant and provide enormously powerful new tools for cell imaging and models for understanding cellular and metabolic processes, which could impact on research across disciplines from systems biology (e.g. studying cellular metabolic pathways), fundamental cell biology, through to medicinal screening and diagnostics (e.g. stem cell identification). Whilst these are high risk areas of research, the collective suite of projects, scientific expertise and state-of-the-art instrumentation is very likely to provide exciting lines for development and together provide an unique opportunity with significantly higher potential than if the projects were run in isolation (particularly in terms of validation). The cross-disciplinary multi project nature of this funding will act as seed to further collaborations not only within the MIB but across the University - pulling together technologists with cellular biologists and medics. Importantly the avenues of communication opened in the sandpit forums and technology event will further catalyse the development of research links and discussion, enabling the technologies to be applied in unique and novel ways. Clearly there will be a strong industrial potential of these developments particularly from the pharmaceutical industry, in identifying the physiological effects of small molecules and mapping of drug distribution within cells. The enabling technology event will provide an opportunity to discuss capabilities with fellow academics, but importantly also with the industrial community, biotechnology business sector and government agencies (e.g. NWDA, KTN), such that we will establish a solid network of connections for future development. Exploitation will be further enhanced by seeking follow on funding to develop proof of principle, or biological application, in order to apply the techniques to answer specific biological and medical questions. Any potential commercial development of the research will be explored through early discussions with the University of Manchester Intellectual Property office, which will be encouraged to take part in events/meetings through out the project.

Publications

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Faria EC (2012) Analysis of single eukaryotic cells using Raman Tweezers. in Methods in molecular biology (Clifton, N.J.)

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Lindstrom, Sara; Andersson-Svahn, Helene (2012) Single-Cell Analysis

 
Description Application of single cell metabolite profiling to optimisation of stem cell bioprocessing
Amount £451,142 (GBP)
Funding ID BB/K011170/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2013 
End 07/2016
 
Description Metabolic profiling of mammalian cells - towards single cell characterisation
Amount £409,057 (GBP)
Funding ID 1364617 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2013 
End 08/2016
 
Description Multi-purpose instrument for advanced Raman spectroscopy techniques
Amount £409,332 (GBP)
Funding ID BB/L014823/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2013 
End 01/2014
 
Description Towards disease diagnosis through spectrochemical imaging of tissue architecture.
Amount £324,000 (GBP)
Funding ID EP/K02311X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 08/2013 
End 07/2016