Creativity@home-Novel Tools for Single Cell Manipulation

Cells which are amongst the smallest units of life are made up of smaller components including lipids and proteins that combine together to perform functions that are vital to the life of the cell. Lipids form the backbone of membranes that help to compartmentalize them whereas proteins are the worker molecules in cells, making, building and moving things throughout. Interestingly, these molecules do not work in isolation, instead they often come together to perform higher order functions and their levels throughout a cell vary both as a function of time and space. They fluctuate as a function of time in response to stimuli, some external and some internal to the cell. Unfortunately, the state of the art in terms of our ability to measure the inner workings of these systems is such that it is still not possible to measure the protein levels in or accurately deliver or remove material to or from a single cell (either to the surface of to a sub-cellular location). This proposal puts forwards a series of feasibility studies to trial a series of new technologies that have the ability to address these technological bottlenecks thereby unlocking the inner workings of cells.

This project will be of benefit to both the academic and industrial communities and is aligned with two of the EPSRC's strategic areas (Nanoscience through engineering to application and Towards Next Generation Healthcare). These feasibility studies aim to build upon two-state-of the-art technologies, namely SDMs and MAC chips that are wholly unique to the UK. If successful, this programme will make a significant and substantial contribution to innovation in UK industry, with a 2-5 year timeframe for academic exploitation and 5-10 year timeframe for commercial realisation. However, the individual elements, e.g. single cell delivery protocols and single cell protein readout modules will be exploitable on shorter time scales of ca. 1-2 years. The development of new tools for the manipulation and analysis of single cells will benefit both sectors and include technical improvements in microfluidics, holographic trapping, protein arrays, and liquid handling platform and proteomic analysis. In addition, the tools and techniques under development here have the potential to provide enhanced capabilities for end-users in basic biology, biomarker discovery, diagnostics and drug discovery. In particular the ability to undertake quantitative spatial and temporal proteomics will provide these sectors with new insights to the spatio-temporal dependencies of cellular signalling pathways. These applications can be directly exploited by the pharmaceutical industry, medical sector, biotechnology SMEs and instrumentation manufacturers. The focus of the programme is concerned with providing tools for the better study of single (including rare) cells. There are obvious benefits to the general population of research that has the potential to impact on our understanding of the relationship between biological heterogeneity and signalling pathway regulation that may result in disease states. This offers the potential to drive novel therapeutic interventions developed in response to single cell behaviours. The ability to deliver material to single cells will impact upon the design of drug delivery systems with tailored drug release kinetics, single cell transfection agents and single cell delivery and transplantation protocols. As the developments of this project go beyond current state-of-the art and provide a range of new platforms for single cell analysis it is inevitable that we will generate intellectual property with significant commercial value. The result will be improved healthcare as well as enhanced economic competitiveness of the United Kingdom by generating wealth and potential future employment. Our strategy for realising the commercial potential of these technology elements is outlined in the accompanying Pathways to Impact document.