Investigations of kinase-mediated cell signaling pathway modulation at the vector-pathogen-livestock interface in vector-borne livestock diseases.

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Vector-borne pathogens, including bacteria and viruses, are an increasing threat to livestock health. Vector-borne diseases that impact livestock species have the potential to disrupt agronomic health and food security with the greatest impacts in developing nations. In addition, climate change has expanded the global distribution of many vector species (e.g. ticks, mosquitoes) resulting in increased likelihood of pathogen introductions to new geographic regions thus increasing the potential impact on other countries that rely heavily on agricultural exports such as Canada. Management of these vectors and vector-borne diseases in livestock species remain a major challenge. Unfortunately, there is a lack of knowledge regarding the molecular events underlying the vector-pathogen-host transmission cycle. My proposed NSERC research program will focus on characterizing vector-pathogen-host transmission cycles in livestock species with a focus on tick-borne (Coxiella burnetti) and mosquito-borne (Rift Valley fever virus; RVFV) diseases. Over the next 5 years, I will investigate the kinase mediated signaling events involved in the transmission cycle. Together with my HQP, I will apply species-specific kinome analysis with kinome peptide arrays to characterize the global activation states of kinases in both vector- and livestock-species. Specifically, we will: i) create vector- and livestock-specific kinome arrays using bioinformatics approaches; ii) characterize both vector-specific and livestock-specific kinome responses following pathogen insult (C. burnetti and RVFV); and iii) determine the functional role of cell signaling pathways and individual kinases identified from our kinome analyses on pathogen persistence and innate immune response dysregulation. By using a complex data approach to investigating the fundamental processes underlying transmission of vector borne diseases, the proposed research will build a wealth of knowledge laying the foundation for future expansion of detailed molecular studies. My program will train HQP with a broad skillset including use of bioinformatics tools, molecular biology, and biochemistry. They will develop expertise in areas of virology, bacteriology, entomology and livestock diseases, thus preparing them for a wide range of careers in the life sciences ranging from microbiology to veterinary medicine.