1a.Objectives (from AD-416)
The current specific aims are: (1) profile the in vivo whole blood RNA and cytokine response to Salmonella Typhimurium (ST) infection in animals with high and low fecal shedding phenotypes; (2) using the same animals in Aim 1, profile the in vitro whole blood RNA and cytokine response to exposure to the general inflammatory endotoxin, lipopolysaccaride; (3) annotate response profiles for common expression patterns and functional themes and develop regulatory network information on response to inflammatory stimuli; and (4) test existing and develop improved predictive models for identifying pigs with decreased fecal shedding at multiple stages of post-infection pro and in naïve pigs.
1b.Approach (from AD-416)
Tests will be performed at BARC to quantitate RNA and protein levels for important markers of inflammatory and infectious processes critical to disease resistance. Simultaneously, the team plans to develop layers of information, based on transcriptional profiling data, on the mechanisms controlling inflammatory and infectious processes critical to disease resistance, and to integrate transcriptional and cromatin binding data available in the pig with similar data in other species to develop higher-level understanding of regulatory mechanisms.
This agreement is aimed at developing predictive models for identifying pigs with superior immune response and improved food safety. The plan is to collate existing data and create new transcriptomic data on healthy animals as well as on the immediate innate immune response to the foodborne pathogen, Salmonella Typhimurium (ST). At ISU, the in vivo whole blood RNA and proliferative responses of ST infected pigs with high and low fecal shedding phenotypes (determined at NADC) will be profiled. At BARC tests will be performed to quantify RNA and protein levels for important markers of inflammatory and infectious processes critical to disease resistance. Overall response profiles will be annotated for common expression patterns and functional themes and regulatory network information developed on response to inflammatory stimuli. The goal is to develop predictive tools for identifying pigs with a low fecal shedding phenotype in naïve pigs and in pigs post-infection. This information will be used to develop a classification tool to predict the important phenotype of shedding of bacterial pathogens associated with animal and pork contamination. If such a predictor can be validated on experimental and field populations, this approach can then be tested for heritability and utility in genetic improvement to potentially decrease Salmonella shedding and pork contamination.