Molecular analysis of baculovirus origins of replication: identification of essential DNA sequences (replicators) and protein factors (initiators)

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Baculoviruses are distinguished by their prolific but restricted multiplication in insects. These invertebrate pathogens are used as vectors for foreign gene expression, potent biological insecticides, and gene transfer vehicles. In Canada, baculoviruses are recognized as safe biological pesticides in integrated pest management programs against economically important pests in agriculture and forestry. Some of our efforts focus on a virus that kills the Spruce budworm, the major Canadian tree defoliator. Baculoviruses have evolved multiplication strategies that limit their replication to invertebrates, but little is known of the critical factors that regulate this strict host specificity. DNA replication is one of the essential processes that likely determines host specificity. The long term goal of my research program is to identify components of the baculovirus replication system that are determinants of virus-host specificity and to use this knowledge to understand the basis for their extremely narrow host range. In an integrated series of experiments using biochemical, genetic, and cell biology approaches, the molecular mechanisms by which early genes of a model baculovirus (AcMNPV) initiate and continue DNA replication will be investigated. An obvious question is where the start points (origins) of replication are located on the AcMNPV genome. Three innovative complementary approaches will be used to investigate this question. Collectively, these studies will provide important insight into the highly conserved pathways of DNA replication that contribute significantly to the baculovirus pathogenicity. The molecular mechanisms by which baculoviruses regulate DNA replication are directly relevant to the use of baculoviruses as safe genetic vectors and biological insecticides. Ultimately, the use of baculoviruses as safe, target-specific insecticides will provide benefits to Canada's environmental sustainability and health status by reducing reliance on chemical pesticides. My program will provide stimulating and challenging projects for high quality training of personnel in an exciting area of natural sciences, insect virology. Importantly, these skills will be applicable and transferable to a multitude of career pathways.