This application is on preventing Human African trypanosomiasis (HAT), which kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. No mammalian vaccines, or effective and affordable therapeutic drugs exist. In contrast, reduction of tsetse populations can be highly efficacious for disease control although traditional strategies have been difficult to sustain because they require extensive community participation in deprived, remote and war-torn regions typically afflicted by this disease. Recombinant technologies now promise the development of novel approaches, including modification of the vector competence of the fly. This application proposes to investigate the fundamental aspects of tsetse immune biology as it relates to the pathogenic trypanosomes it transmits, and the obligate mutualist symbionts it relies on for fecundity. The application has two goals: (1) to investigate the molecular basis of tsetse's refractoriness to trypanosome transmission with a focus on the role of pathogen recognition molecules, and (2) to understand the responses and the evolutionary dynamics of tsetse's immune reactions that regulate symbiotic homeostasis and vector competence. Identification of host immune proteins that result in parasite resistance can strengthen efforts that can reduce tsetse's vector competence via genetic modification. Understanding the mechanism of tolerance to symbiotic fauna may result in novel vector control strategies that aim to reduce tsetse's fecundity.

Public Health Relevance

This grant will investigate the molecular and biochemical mechanisms in the insect tsetse fly that enable the transmission of the parasite African trypanosome, the causative agents of Sleeping Sickness disease in humans. The ultimate goal is to be able to interfere with parasite transmission in the fly.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051584-09
Application #
8306932
Study Section
Special Emphasis Panel (ZRG1-IDM-M (02))
Program Officer
Costero, Adriana
Project Start
2001-12-31
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
9
Fiscal Year
2012
Total Cost
$472,521
Indirect Cost
$187,010
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
Aksoy, Emre; Vigneron, Aurélien; Bing, XiaoLi et al. (2016) Mammalian African trypanosome VSG coat enhances tsetse's vector competence. Proc Natl Acad Sci U S A 113:6961-6
Zhao, Xin; Alves e Silva, Thiago Luiz; Cronin, Laura et al. (2015) Immunogenicity and Serological Cross-Reactivity of Saliva Proteins among Different Tsetse Species. PLoS Negl Trop Dis 9:e0004038
Hrusa, Gili; Farmer, William; Weiss, Brian L et al. (2015) TonB-dependent heme iron acquisition in the tsetse fly symbiont Sodalis glossinidius. Appl Environ Microbiol 81:2900-9
Aksoy, Emre; Telleria, Erich L; Echodu, Richard et al. (2014) Analysis of multiple tsetse fly populations in Uganda reveals limited diversity and species-specific gut microbiota. Appl Environ Microbiol 80:4301-12
Weiss, Brian L; Savage, Amy F; Griffith, Bridget C et al. (2014) The peritrophic matrix mediates differential infection outcomes in the tsetse fly gut following challenge with commensal, pathogenic, and parasitic microbes. J Immunol 193:773-82
Telleria, Erich Loza; Benoit, Joshua B; Zhao, Xin et al. (2014) Insights into the trypanosome-host interactions revealed through transcriptomic analysis of parasitized tsetse fly salivary glands. PLoS Negl Trop Dis 8:e2649
Aksoy, Serap; Weiss, Brian L; Attardo, Geoff M (2014) Trypanosome Transmission Dynamics in Tsetse. Curr Opin Insect Sci 3:43-49
Brelsfoard, Corey; Tsiamis, George; Falchetto, Marco et al. (2014) Presence of extensive Wolbachia symbiont insertions discovered in the genome of its host Glossina morsitans morsitans. PLoS Negl Trop Dis 8:e2728
Aksoy, Serap; Attardo, Geoffrey; Berriman, Matt et al. (2014) Human African trypanosomiasis research gets a boost: unraveling the tsetse genome. PLoS Negl Trop Dis 8:e2624
International Glossina Genome Initiative (2014) Genome sequence of the tsetse fly (Glossina morsitans): vector of African trypanosomiasis. Science 344:380-6

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