Human African trypanosomiasis (HAT) kills thousands of people each year in sub-Saharan Africa. The disease is caused by the protozoan African trypanosomes, and is transmitted to the mammalian host by the tsetse fly. Control of the parasite in its mammalian host is difficult. Recent advances in vector biology promise the possibility of modifying the parasite transmission ability of the fly (vector competence). Replacement of parasite susceptible fly populations with their refractory counterparts can provide a new tool for disease control. Understanding the interactions between the tsetse vector and trypanosomes is essential for generating knowledge in support of these new technologies. This exploratory application will study the large expressed sequence tags (ESTs) that have been generated from various tissues of tsetse including midgut, fat body, salivary glands, reproductive tissues and from immature developmental stages. The overall goal is to mine these gene discovery projects to identify candidate products involved in trypanosome differentiation and maturation process in tsetse. This application will build a foundation for studying tsetse-trypanosome interactions in the salivary glands and for investigating the molecular aspects of parasite gene expression biology during its development in the salivary glands. It will identify putative tsetse proteins, which influence trypanosome biology by using in silico approaches and expression profiling and functional genomics tools. It will also determine trypanosome proteins associated with metacyclogenesis during development in the fly by obtaining a quantitative measurement of gene expression levels from salivary gland-derived trypanosome cells.

Public Health Relevance

The project will use bioinformatics tools to identify important salivary gland proteins from the tsetse fly expression database. Specifically proteins involved in the African trypanosome parasite transmission to humans will be characterized. The parasite is the causative agent of human sleeping sickness disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI076879-02
Application #
7630560
Study Section
Special Emphasis Panel (ZRG1-IDM-M (02))
Program Officer
Costero, Adriana
Project Start
2008-06-15
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2011-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$247,818
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Sistrom, Mark; Evans, Benjamin; Benoit, Joshua et al. (2016) De Novo Genome Assembly Shows Genome Wide Similarity between Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. PLoS One 11:e0147660
Savage, Amy F; Cerqueira, Gustavo C; Regmi, Sandesh et al. (2012) Transcript expression analysis of putative Trypanosoma brucei GPI-anchored surface proteins during development in the tsetse and mammalian hosts. PLoS Negl Trop Dis 6:e1708
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