Gastrointestinal parasites represent one of the major drivers of global disease burden, particularly neglected tropical diseases, with nearly 800 million infected worldwide. In the U.S., for example, parasitic infections are known to disproportionately affect impoverished and under-represented minority populations, and preliminary estimates suggest potentially hundreds of thousands of individuals are infected, making it one of the top health disparities in the U.S. The investigators will conduct basic research on how genetic variation confers gastrointestinal parasite infection resistance or susceptibility in a primate species. The results of this study will provide a more complete understanding of the biological mechanisms that underlie disease susceptibility, which is fundamental to the development of more effective prevention and treatment strategies for infectious diseases. The scientific value of this project will be further amplified through the creation and implementation of an educational module in disease genetics developed to engage Oregon middle-school students traditionally underrepresented in STEM fields.
The specific goals of this project are to identify regulatory genetic variants in immune genes that are associated with parasite infection in the red colobus monkey, and demonstrate that those variants have a causal relationship with infection intensity through their effects on gene expression. DNA variant/infection associations will be determined through a combination of DNA sequencing and classical parasitological approaches. The ability of regulatory variants to drive differential gene expression will then be tested in-vitro using bioluminescent reporter assays in multiple cell lines. Predictions based on cell experiments will then be tested in-vivo using RNA-seq. This study will advance our understanding of the evolution of immunity to pathogens and provide a comprehensive, mechanistic, explanation for observed genotype-parasite infection intensity associations.
