Tool for studying essential gene function in Cryptosporidium parvum

AbstractCryptosporidium is a protozoan parasite that causes diarrheal disease (cryptosporidiosis) and deaths in youngchildren, and immunocompromised individuals such as HIV/AIDS patients and transplant recipients. Recentglobal epidemiological studies report that Cryptosporidium is the second leading pathogen after rotavirus tocause life-threatening diarrhea in infants and toddlers. Recurrent episodes of Cryptosporidium infection areassociated with chronic malnutrition, growth stunting and impaired cognitive development in young children. Theinfection occurs through ingestion of water and food contaminated with oocysts. Since these ?spore-like? oocystsare resistant to standard disinfection procedures, waterborne outbreaks are very common and reportedworldwide. Infact, Cryptosporidium is responsible for 50% of disease outbreaks linked to recreational water usein the US. There are no effective drugs or vaccines to treat or prevent cryptosporidiosis. The only FDA approveddrug, Nitazoxanide provides little to no relief to young children or HIV/AIDS patients that need it the most.Therefore, there is an urgent need to develop new drugs and vaccines to reduce the burden of cryptosporidiosis.To discover novel therapeutics, it is crucial to dissect Cryptosporidum biology and identify its ?Achilles heel?.Currently, there is very limited understanding of parasite biology due to lack of methods to continuously cultureCryptosporidum in the laboratory, poor animal models, and lack of molecular tools to genetically modify thispathogen. Recently, we have developed a robust technology to genetically manipulate C. parvum, and an animalinfection model to propagate these parasites, thus providing an exciting opportunity to answer fundamentalquestions regarding parasite biology, virulence and disease pathogenesis. Despite these advances, we are stilllacking tools to study genes essential for parasite survival, since deleting these genes would be lethal to theparasite. Thus, the goal of this project is to apply our expertise in molecular genetics and develop a powerfulconditional protein degradation tool to unravel the function of essential genes in Cryptosporidium. Elucidation ofthe function of essential genes throughout the parasite lifecycle would ultimately lead to the development ofnovel drugs and vaccines to treat cryptosporidiosis.