The parasite *Cryptosporidium* injects a protein called SRP into human gut cells to cause disease, and researchers have no idea how it does this. This matters because *Cryptosporidium* is a leading cause of diarrhoeal disease in children in developing countries and causes frequent outbreaks worldwide. Unlike many other intracellular pathogens, scientists know nothing about how this parasite exports its weapons into host cells or what those weapons actually do. The project will map where SRP goes inside the cell, identify the parasite's hidden export machinery, and test how these exported proteins drive infection and immune responses in mice. This is fundamental science. There is no immediate vaccine or drug to test. But understanding the parasite's export system could reveal entirely new targets for treatment. Similar work on other pathogens—such as the type III secretion system in bacteria—led directly to novel anti-infective strategies. A clearer picture of how *Cryptosporidium* hijacks its host could eventually shift the approach to a disease that currently has no effective vaccine and limited treatment options.
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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.
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