Manipulating Molecules with unprecedented resolution and control - the Lumicks C-trap
Lead Research Organisation:
University of Nottingham
Department Name: School of Life Sciences
Abstract
The aim of this proposal is to purchase a Lumicks C-trap to be housed at the University of Nottingham. Here it will be run as a facility instrument delivering a unique and much needed capability to Scientists based in the East Midlands and South Yorkshire (see letters of support from the Universities of Leicester, Loughborough, Sheffield, and Nottingham Trent).
The C-trap is unique in its ability to manipulate (bend, move and stretch) single molecules, such as DNA and proteins, whilst allowing simultaneous imaging of these molecules. It is a highly specialised instrument for studying the dynamics of individual single molecules. This is achieved by combining optical trapping, micro-fluidics and microscopy (fluorescence or label-free). It will be used to study a variety of biological processes such as cytoskeletal dynamics, DNA repair mechanisms, intracellular transport, chromosome structure, biomaterials and the assembly and disassembly of protein droplets.
At Nottingham we have identified three initial projects we plan to target. These are i) measurement of the biophysical properties of the chromosome periphery; ii) how the cytoskeleton orchestrates cell division and allows cells to withstand force and iii) the role of DNA repair mechanisms in cancer biology. Each of these projects will be enhanced by access to a C-trap as this instrument will permit experiments that would not be otherwise possible.
The unique capabilities and the wide range of possible applications mean this instrument opens unexplored possibilities for researchers working on biological questions to understand the foundations of life and health. It is therefore vital that Nottingham and surrounding regions have access to this transformative technology to expand the unique knowledge and capability of researchers in the region to deliver world leading bioscience research.
The C-trap is unique in its ability to manipulate (bend, move and stretch) single molecules, such as DNA and proteins, whilst allowing simultaneous imaging of these molecules. It is a highly specialised instrument for studying the dynamics of individual single molecules. This is achieved by combining optical trapping, micro-fluidics and microscopy (fluorescence or label-free). It will be used to study a variety of biological processes such as cytoskeletal dynamics, DNA repair mechanisms, intracellular transport, chromosome structure, biomaterials and the assembly and disassembly of protein droplets.
At Nottingham we have identified three initial projects we plan to target. These are i) measurement of the biophysical properties of the chromosome periphery; ii) how the cytoskeleton orchestrates cell division and allows cells to withstand force and iii) the role of DNA repair mechanisms in cancer biology. Each of these projects will be enhanced by access to a C-trap as this instrument will permit experiments that would not be otherwise possible.
The unique capabilities and the wide range of possible applications mean this instrument opens unexplored possibilities for researchers working on biological questions to understand the foundations of life and health. It is therefore vital that Nottingham and surrounding regions have access to this transformative technology to expand the unique knowledge and capability of researchers in the region to deliver world leading bioscience research.
Technical Summary
The C-trap enables live simultaneous manipulation of objects, force measurement, distance acquisition and observation of single fluorescently-labelled or label free molecules, and captures all relevant information on the biological process under study at the same time. This is combined with multi-channel micro-fluidics allowing introduction of precious reagents in an exquisitely controlled manner, facilitating the assembly of a wide range of complex, multi-step single molecule assays.
The system has an automated workflow to aid the researcher in setting up single molecule experiments and an intuitive user interface making the instrument suitable for a multi-user facility. The simple and fast workflow enables the execution of for example bead trapping, molecule tethering and subsequent manipulation in under two minutes. This boosts experiment throughput allowing rapid acquisition of replicate experiments, an essential requirement in single molecule experimentation.
We have identified a large user group of researchers for whom access to a C-trap will provide a step-change in ability to push the boundaries of bioscience knowledge. We have identified 3 initial target projects: 1) biophysics of the chromosome periphery, 2) the cytoskeleton in cell maintenance and division, 3) the molecular mechanisms of DNA repair in cancer biology. The C-trap will be transformative for each of these projects, providing access to experiments not possible with existing equipment at UoN.
The unique capabilities and the wide range of possible applications mean this instrument opens unexplored possibilities for researchers working within the BBSRC remit. It is therefore vital that Nottingham, the East Midlands and South Yorkshire region has access to this technology to maintain the ability of our researchers to deliver world leading bioscience research.
The system has an automated workflow to aid the researcher in setting up single molecule experiments and an intuitive user interface making the instrument suitable for a multi-user facility. The simple and fast workflow enables the execution of for example bead trapping, molecule tethering and subsequent manipulation in under two minutes. This boosts experiment throughput allowing rapid acquisition of replicate experiments, an essential requirement in single molecule experimentation.
We have identified a large user group of researchers for whom access to a C-trap will provide a step-change in ability to push the boundaries of bioscience knowledge. We have identified 3 initial target projects: 1) biophysics of the chromosome periphery, 2) the cytoskeleton in cell maintenance and division, 3) the molecular mechanisms of DNA repair in cancer biology. The C-trap will be transformative for each of these projects, providing access to experiments not possible with existing equipment at UoN.
The unique capabilities and the wide range of possible applications mean this instrument opens unexplored possibilities for researchers working within the BBSRC remit. It is therefore vital that Nottingham, the East Midlands and South Yorkshire region has access to this technology to maintain the ability of our researchers to deliver world leading bioscience research.
