CRYPTOEXPORT: Exploring virulence and effector export in the intestinal parasite Cryptosporidium

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Cryptosporidiosis is a leading cause of diarrheal disease and a major contributor to global morbidity and mortality. Although the burden of disease is primarily carried by children in developing countries, Cryptosporidium is a ubiquitous intestinal parasite with frequent outbreaks around the world. Intracellular pathogens, such as Cryptosporidium, are known to have developed sophisticated export systems that transport effectors into their host cell, helping the pathogen to evade detection and destruction. For Cryptosporidium, nothing is known about how it transports effectors into its host cell and what these effectors do. Here, we introduce the Cryptosporidium serine repeat protein, or SRP, a novel host-exported effector that is required for virulence and propose to address the following questions: How does the SRP effector function? Here we will determine the subcellular location of this critical virulence factor throughout the parasite life cycle, then systematically dissect SRP function and establish whether this function is conserved across different species of the parasite. How does Cryptosporidium export effectors? Here we will leverage SRP to identify other exported effectors and parasite factors that play a role in this export pathway, including the unique and unknown transport machinery of Cryptosporidium. How do exported effectors influence Cryptosporidium virulence and immunity? Here we will use our mouse model of infection to investigate how exported effectors contribute to parasite burden, disease pathology, and the host immune response.