Grant: Emerging Team Grant: Regenerative Medicine and Nanomedicine - LOI

Herein we will apply nanotechnology solutions to critical impending health issues. Specifically we will use innovative fluorescence single molecule methods to investigate the molecular structure and dynamics of enzymes which are involved in viral genome replication (genome-replication machinery) including helicases, transcriptases and polymerases. We seek to provide a -molecular movie- with nanometer spatial resolution and microsecond time resolution, enabling, the characterization of the dynamics and mechanics of the genome-replication machinery for Hepatitis C virus, HIV and human papillomavirus. We will also address how the interaction of the gene-replication machinery with small-molecule inhibitors affects the structure and function of the enzymes, and further we will study the underlying biochemical mechanisms of resistance. We will ultimately develop a state-of-the-art nanotechnology platform which we will translate to other viral systems, what will be instrumental in developing high throughput tests to monitor the action mechanism of novel drugs on the viral enzymes with unique mechanistic insight. Ultimately, the single molecule mechanistic studies proposed herein have the potential to open new dimensions with regards to a detailed understanding of the fundamental process of viral genome synthesis which in turn can be translated in antiviral drug discovery and development programs.