| EPSRC Reference: |
EP/H004238/1 |
| Title: |
International Collaboration in Chemistry: Spatially resolved measurements of cellular releasates |
| Principal Investigator: |
McGloin, Professor D |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Electronic Engineering and Physics |
| Organisation: |
University of Dundee |
| Scheme: |
Standard Research |
| Starts: |
01 March 2010 |
Ends: |
30 June 2013 |
Value (£): |
283,742
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| EPSRC Research Topic Classifications: |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
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| Panel History: |
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Summary on Grant Application Form |
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Our understanding of the cell and of cellular interactions is greatly advanced by the development of high-resolutionimaging techniques, from bright-field optical and confocal fluorescence microscopy to electron microscopy and scanningprobe microscopy. Optical microscopy provided the first visualization of a single cell and the organization of multiple cellsto form complex cellular networks we call tissues. In combination with immunostaining, electron microscopy offered keyinsight into the localization of proteins and the organization of subcellular architectures with unprecedented spatialresolution. Fluorescence microscopy has provided striking visualizations of the dynamic environment inside a cell, suchas protein trafficking visualized using green fluorescent proteins.Despite these advances, the visualization of cellular releasates - chemicals released to initiate cell signalling response -has been much more challenging. For certain small molecules, such as calcium and zinc, it is possible to usefluorescence indicators to monitor their spatiotemporal changes. For most other cellular releasates, such as cytokines,metabolites, and peptides, it has been much more difficult to map from where and when they are released. Yet, the abilityto follow the such release pattens is critical in deciphering the complex chemical communications between cells. In thenervous system, for example, the pattern of neurotransmitters and peptide neuromodulators released directly dictatespatterns of activity of the entire network. In the immune system, formation of the immunological synapse results inclustering of cytokine receptors and causes T cells to secrete their vesicular contents..Several techniques have been developed towards addressing this need to monitor cellular releasates. For small electroactivemolecules, Wightman and co-workers have pioneered the use of microelectrodes for the electrochemical detectionof quantal releases from cells, which has been applied towards understanding drug addiction and the brain rewardsystem. Sweedler and co-workers have demonstrated the use of single-bead solid-phase extraction and massspectrometry for measuring various secreted peptides, and Kennedy and co-workers have studied the secretion fromsingle islets of Langerhans using electrophoresis-based immunoassay. Here, we propose to develop a newmethodology, based on holographic optical trapping and ultrasensitive single-molecule bead-based assay, for monitoringthe spatiotemporal dynamics of cellular releasates. We believe this method will offer significant improvements in spatialresolution and sensitivity over current techniques.This project is joint with Prof. Daniel Chiu's group at the University of Washington in Seattle. The Chiu group are leadingexperts in microfluidic design with particular applications in biosensing. The two groups will combine their microfluidicsand optical knowledge to try and create new techniques and devices for biochemical sensing.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.dundee.ac.uk |