Tools for live cell imaging of biomolecular interactions

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Sensitive molecular imaging techniques represent the future of diagnostics. Fundamental research is needed to develop molecular probes that help to visualize disease states combined with nanoscale resolution imaging techniques allows for the detection of molecular determinants of disease at the cellular stage often before the phenotype of disease is apparent in a given tissue. In this discovery grant we propose to perform fundamental research into the chemistry and biology of different probe designs in order to develop and investigate new molecular imaging tools for the visualization of pathogenic RNA and to visualize host-virus interactions at the cellular membrane. These two techniques will be applied to visualize hepatitis C virus (HCV) RNA in cells and tissues, as well as image at the nanoscale interactions that lead to HCV cell entry. Although the tools and approaches may be applied more broadly we have chosen to demonstrate them on HCV because it is a virus that chronically infects more than 250,000 Canadians and it is difficult to detect. Novel and highly sensitive probes will be synthesized for the direct imaging of hepatitis C virus RNA in infected cells. A number of probe designs will be explored. Once the probes are constructed, in vivo imaging of HCV-infected cells will be conducted. We also propose to perform fundamental studies on different probe architectures for the purposes of investigating molecular processes involved during cell entry processes using nanoscale imaging techniques being developed in our lab.