Low-light-level camera for single-molecule imaging

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The development of single-molecule detection techniques has led to a revolution in our ability to study the physical aspects of biological molecules.  Features that have been obscured when averaging the behaviour of molecules in solution can now be studied in exquisite detail.  This application is for a camera that can image moving, dim objects such as single molecules of DNA in solution.  The main application will be to an experiment that probes DNA replication - how the genetic information in a cell is passed on to its descendants - by looking at replication in a single cell.  Previous work has depended on extracting DNA from many cells.  A major difficulty of those experiments is that the cell cycles of different cells are not well-synchronized.  Single-cell experiments will resolve that problem.A second application will be to develop a way of trapping single molecules so that their behaviour can be probed over long times, in great detail.  For this, a sensitive, rapid camera is needed to image the molecule and determine its position.  Then fluctuations in that position can be compensated by "kicks" that move it back to the desired location.  We will use such a trap to probe how DNA interacts with other molecules such as proteins.  These are basic steps in many biological processes, and the kind of information we can gather here will be unique and uniquely valuable for giving new understanding.