Diarrhea is one of the leading causes of death among children under five globally. More than one in ten child deaths - about 800,000 each year - is due to diarrhea. Today, only 44% of children with diarrhea in low- income countries receive the recommended treatment, and limited trend data suggest that there has been little progress since 2000. In 2013, a massive clinical and epidemiological study1 involving 22,500 children from Africa and Asia revealed - unexpectedly - that the protozoan parasite Cryptosporidium is one of four pathogens responsible for the lion's share of severe diarrhea in infants and toddlers. Vaccines and treatments are already available or fast being developed for three of the four pathogens identified: rotavirus, Shigella bacteria and enterotoxigenic Escherichia coli. But for 'crypto', there is no fully effective drug treatment or vaccine, and the basic research tools ad infrastructure needed to discover, evaluate and develop such interventions are mostly lacking. Cryptosporidium is a zoonotic apicomplexan protist parasite that causes gastrointestinal illness with diarrhea in humans and animals. However, the disease is most serious in children and immunocompromised individuals, especially malnourished children, where the infection can aggravate poor nutritional conditions, lead to impaired immune response, chronic infection and long-term negative impact on growth and development. Cryptosporidium parasites are found globally. In the US, an estimated 748,000 cases of cryptosporidiosis occur each year. My long-term goal is to help with the treatment/prevention of Cryptosporidium infections. To achieve this goal I will use bioinformatics to help test the hypothesis that C. baileyi may be a suitable animal model for the human-infecting C. parvum and C. hominis. A comparative genomic analysis of C. baileyi as well as comparative transcriptional profiles will be performed. A C. baileyi model is important because this species can complete its lifecycle in experimentally tractable chicken eggs unlike other species which require cattle or gnotobiotic pigs e.g. C. hominis and C. parvum. In vitro culture is not yet available for any species. To test my hypothesis about the model, I will conduct the first ever annotation of C. baileyi, compare its genome annotation to human-infecting species of Cryptospordium and use RNA-Seq data generated from C. baileyi to compare the gene expression to that of C. parvum (the only other organism gene expression data is available for). My results will contribute to a new animal model for Cryptosporidium.

Public Health Relevance

(page 1-80) 2-3 lay sentences Cryptosporidium is a microscopic parasite that is responsible for the second largest number of diarrhea cases globally. For Cryptosporidium, there is no fully effective drug treatment or vaccine, and the basic research tools and infrastructure needed to discover, evaluate and develop interventions for this parasite are mostly lacking. My project proposes to use genome comparisons to assess the suitability of a related, easy to culture bird- infecting species as a possible model for study.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Adger-Johnson, Diane S
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University of Georgia
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