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Details of Grant 

EPSRC Reference: EP/D501342/1
Title: Control of the Single Molecule Fluorescence Cycle - A Feasibility Study
Principal Investigator: Bain, Professor AJ
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Cancer Research UK Universite De Renne (CNRS)
Department: Physics and Astronomy
Organisation: UCL
Scheme: Standard Research (Pre-FEC)
Starts: 01 March 2006 Ends: 31 August 2007 Value (£): 91,927
EPSRC Research Topic Classifications:
Chemical Biology Light-Matter Interactions
Scattering & Spectroscopy
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
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Summary on Grant Application Form
Control of Single Molecule Fluorescence (or Road Safety for Biomolecules)The life of a single bio-molecular probe that is undergoing repetitive (continuous) excitation by a pulsed or continuous wave laser is somewhat akin to a pedestrian randomly setting out to cross a (fairly) quiet stretch of road. Given a push (a burst of photons passing through the sample) there is a finite probability that the pedestrian starts their journey across the road, the successful outcome of which is reaching the other side -this is equivalent to the emission of a photon and the molecule returning to the safety of its electronic ground state. However whilst in transit, equivalent to being in an excited electronic state, the pedestrian may unfortunately encounter a pot hole or imperfection in the road surface, with the unfortunate consequence that their foot becomes trapped and that progress to the other side is halted. The pedestrian cannot reach the safety of the pavement and it takes considerably longer for them to extricate their foot than the average time it would otherwise take them to cross. There are thus periods where the pedestrian's journeys to and fro are interrupted, in the case of a molecule it becomes 'dark' and no fluorescence photons are emitted for considerable (c.a. milliseconds) periods of time. Unfortunately this is not the end of the story, whilst trapped in the pot hole the pedestrian is in greater danger of being struck by a bus or some other similarly dangerous vehicle (in the case of a molecule trapped in a 'dark' state the fatal collision is with an oxygen molecule or some other reactive species that changes it chemically). The pedestrian's random journeys into the road are over and in the molecular world the molecule is photochemically dead.The research we propose to undertake is to help the 'pedestrian' make it across the road safely by waiting for a reasonable time for the journey to be made (the average crossing time) this is generally short in comparison to the average time it takes for the pedestrian to stumble into a pothole. We then add a second 'push'; this propels the pedestrian (if they have not already reached it) swiftly to the safety of the pavement. Judging the conditions by which we can optimise our chances of guiding the pedestrian across the road depends on the fundamental properties of the pedestrian, the probability of trapping taking place and the difficulty of extrication from the trap. The push that we provide to the pedestrian is an optical one and needs to be carefully tailored to the pedestrian as well. This requires us to have detailed knowledge of the pedestrian's random walk and we will obtain this from time resolved single molecule fluorescence and fluorescence correlation studies. We will also need to determine how susceptible (on average) the pedestrian is to being pushed. All this data will be input into a random walk simulation which includes our optical 'push', from this we can see what kind of push is appropriate and to set up a two pulse laser experiment in which the 'street' is the confocal volume of an inverted microscope and our observation of the pedestrian's repeated journeys is via the electrical signals produced by sensitive single photon detectors which have been donated to the project by Cancer Research UK.We have several kinds of 'pedestrians' to work with; our collaborators in France lead the world in developing molecules who can be propelled into the street with little effort, we have found that some are also very amenable to being pushed but we have yet to see how they behave individually. Our collaborators at Cancer Research UK use green and yellow fluorescent proteins as natural labels to monitor conformational changes in cell-signaling proteins and we will investigate the possibility of optically controlling the fluorescence cycle (safer road crossing) in these as well.
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