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January 2010 - March 2011

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University of Minnesota Twin Cities
College of Veterinary Medicine
Department of Veterinary Biomedical Sciences

PI: Mark S. Rutherford

Cryptosporidium Gene Expression During Host/Pathogen Interactions

Cryptosporidium is a well-recognized cause of diarrhea and morbidity in humans and animals throughout the world. Due to its ability to resist traditional disinfectant protocols and persistence in the environment, Cryptosporidium is an important water- and food-borne human pathogen. Cryptosporidium is an obligate intracellular pathogen that progresses through a complex life cycle involving multiple asexual and sexual developmental stages, where all parasite development occurs within the intestinal epithelial cells (IEC) of the host. Despite the existence of the complete genome sequence of both organisms, no essential parasite genes have been exploited for therapeutic use. The completion of the C. parvum genome has revealed an extremely streamlined metabolism that is lacking many of the important de novo biosynthetic pathways, including those for amino acids, purines, pyrimidines, and fatty acids. Although this reflects the extreme nature of the its parasitism, almost nothing is known regarding the mechanisms that determine host tissue and cell specificity or the nature of the biochemical interaction between the parasite and host cells.

The central hypothesis of this project is that Cryptosporidium must actively manipulate host cell gene expression and biochemical pathways to circumvent intrinsic defense programs and complete its developmental life cycle. Bioinformatics using these researchers’ transcriptome data will identify key host cell pathways that must be usurped for life cycle progression or intrinsic host cell pathways that subvert the parasitism to provide potential therapeutic targets of the host cell. They will then use an approach to modify the expression of specific parasite genes by the introduction of in vitro transcribed RNA into Cryptosporidium oocysts. Gene products from this RNA will either serve as "bait” for protein-protein interaction assays or will be used to track the location of parasite proteins.

Group Members

Shin Enomoto, Research Associate
Cheryl A. Lancto, Staff
Vary Mauzy, Graduate Student