Grant: Discovery Grants Program - Individual

All eukaryotic cells have a distinct nucleus containing, among other things, the genetic blueprint of the organism to which the cell belongs. Carrying out the instructions contained in the genetic blueprint requires trafficking of molecules between the cytoplasm and the nucleus - a process known as nuclear transport. This trafficking is essential to all eukaryotic cells, and also regulates many aspects of cell physiology. Despite the obvious importance of nuclear transport and despite many recent advances in this field, many aspects of its molecular mechanism, its structural basis, or its regulation remain elusive. The long-term objective of my research program is to elucidate the mechanisms by which macromolecules enter the nucleus. Because many viral pathogens undertake their replication within the nucleus, and therefore must deliver their genome and subviral particles into the nucleus of their host cells, we are using viruses as tools to understand the molecular mechanisms for nuclear transport. In our studies we use a combination of structural, functional, biochemical, and genetic approaches. In addition, we extensively use high-resolution electron microscopy to track the virus' movement and entry into the nucleus. Findings from these studies will shed new light on the fundamental mechanisms of nuclear transport, and will make significant contributions to understanding the transport of viruses into the nucleus, and more generally the delivery of DNA to nucleus, which is for example also an essential step in transfection and gene delivery in gene therapy. Therefore, our studies of nuclear trafficking of viruses could also help developing efficient transfection techniques and gene therapy vectors.