The long-term goal of this collaborative work is to identify fundamental genetic controls of differentiation, invasion, and pathogenesis of C. parvum, and of the infected host cell during infection by Cryptosporidium. The genome sequences of C. hominis and C. parvum, previously called genotype 1 (human) and genotype 2 (bovine), respectively, are now available as a resource for identifying genetic processes associated with parasite development or host cell response. In this project, we propose to convert genomic sequences into comprehensive DNA microarrays that can be used to probe these processes.
This proposal builds on the combined expertise of the VCU and Tufts University groups in the biology and genomics of C. parvum, and on extensive experience with microarrays. The analysis of host cell and parasite gene expression on a global scale is a powerful method for understanding host-pathogen interaction. Although gene expression studies have been performed with T. gondii and Plasmodium species, Cryptosporidium is unique because, unlike other apicomplexan parasites, its life cycle evolves in a single host and because of the unique compartment in which it resides in the cells of the host intestinal epithelium. Global gene expression analysis methods, combined with genome-wide sequence information, and eventually proteomic analysis, will advance several areas of research on this parasite; e.g., our understanding of parasite biology and metabolism and of the host-parasite interactions. This information will facilitate identification of new vaccine and drug targets.
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