Research On Infectious Diseases of Animals and Their Management in Montana

The short- and long-term objectives of research in MBI are the development of new drugs, vaccines, and diagnostic tools for fighting infectious diseases of livestock, humans, and wildlife. This includes scholarly discovery and dissemination of science and technology related to diseases affecting livestock and wildlife, as well as zoonotic diseases that can be transmitted to humans. Newly awarded MAES and/or initiated projects that have also been peer-reviewed include:1. Molecular pathogenesis of West Nile Virus (New MAES Project). West Nile virus (WNV) is an emergent neuroinvasive pathogen that causes severe illness in a wide range of vertebrates, including horses. In recently published work, we reported a restriction that limits the number of alphaherpes virions infecting neurons (Taylor et al., 2012). I propose a series of experiments that aim to identify if neuroinvasive spread of WNV is restricted in the number of virions transmitted between cells and characterize the cellular
antiviral signaling activated neuronal infection of WNV. By characterizing neuroinvasive spread of WNV, we will begin to understand how neuroinvasive viruses are controlled during zoonotic infections and understand the impacts on viral population biology and pathogenesis. IBC Protocol Numbers: 032-2014 (WNV), 08-2015 (recombinant Baculovirus) and IACUC Protocol: 2013-282. Genome editing though use of CRISPR technology (New MAES Project). Cas9 is a new RNA-guide technology that permits rapid and precise manipulation of plant and animal genomes. This new gene knockout system is revolutionizing molecular biology and the value of this technology is currently estimated in the billions. However, this technique has been primarily restricted to generating gene knockouts (i.e. search and delete functions). Knockouts are critical for determining the biological function of a specific gene, but the genetic basis of many plant and animal diseases are already known and the next major advance will
be to design methods that facilitate precise repair of defective genes (i.e. search and replace functions). Here we propose lentiviral delivery of Cas9 to generate a genome-wide knockout library in human cells that will identify novel pathways that enhance Homology Directed Repair (HDR) of double-stranded DNA breaks. We anticipate that many of the human genes involved in HDR will have conserved functions in other animals and plants. Results from this screen will provide fundamental new insight into DNA repair mechanisms, and provide a foundation for designing the next generation of tools for "correcting" genetic disorders and engineering Ag related products for resistance to environmental stress, and improving food security for the rapidly expanding population. IBC Protocol 024-2014.3. Mucosal immunology in pigs (NIH pilot grant peer-review). This study seeks to obtain pilot data to evaluate the current zoonotic threat and the mechanisms of gastric pathogenesis for human Helicobacter
suis (H. suis) infection. H. suis is a stomach-dwelling bacterium naturally found in pigs that has been associated with gastric lesions including gastric cancer in humans. The overall hypothesis is that H. suis is a relevant zoonotic pathogen that disrupts human gastric epithelial cell function by triggering inflammatory signaling. In summary, our study will elucidate inflammatory pathways induced by H. suis and will determine whether there is a need for further research into zoonotic H. suis infection. IBC protocol 042-2014.4. New vaccine development for Coxiella burnetii and Brucella abortus and melitensis (new project). Using novel virus-like particles, unique vaccine constructs are being developed for effective T cell immune responses against Coxiella and Brucella.5. Funding will also be provided for new faculty who develop animal health related projects. Possible projects include disease ecology of pneumonia in bighorn sheep and domestic sheep, and scouring diseases in cattle.