High speed super-resolution imaging with the OMX microscope. (360G-Wellcome-094587_Z_10_Z)

The imaging of fluorescent proteins in living cells has proved a powerful approach in cell biology, but many processes cannot be visualised because of the limited sensitivity and resolution of current microscopes. We seek funding for an OMX imaging system that overcomes these limitations. The OMX has a simplified light path that makes it much more sensitive than standard microscopes, and is configured to image three wavelengths simultaneously. These increase the speed of time-lapse imaging by an order of magnitude, allowing the detection of faint, fast-moving fluorescent objects that are otherwise invisible. The greater sensitivity also allows the use of lower levels of illumination, which reduces photo-toxicity and photo-bleaching for long-term time-lapse imaging of light-sensitive samples. Another major innovation is the use of structured illumination to break the diffraction limit, doubling resolution to 110nM. The OMX can perform super-resolution imaging deep inside cells at several frames/second (unlike other super-resolution microscopes), and can therefore reveal dynamic features of subcellular structure at a new scale. This microscope will be a shared resource for all cell biologists in Cambridge, and will be used to investigate topics such as mRNA trafficking, neuronal polarity, the spindle checkpoint and DNA damage foci.