The focus of this proposal is to identify molecular targets of tsetse fly reproductive physiology for the development of novel biological control strategies for the prevention of disease transmission. Tsetse are the vectors of trypanosomiasis in both humans and animals in sub-saharan Africa creating major health and economic problems. There are no vaccines to control disease in the mammalian host and only a single and highly toxic drug is available for treatment of late stage infections. Vector control methods, such as trapping and insecticide spraying, are effective in reducing fly challenge. Vector reduction methods are especially effective due to the low fly population numbers resulting from tsetse's slow reproductive rate. Tsetse has an unusual reproductive biology as they only develop one offspring at a time and give birth to a fully developed larva. Reproduction in tsetse is also unique in that it requires the presence of obligate mutualist symbiotic bacteria. Nutrients for the developing intrauterine larva are supplied entirely by the mother. Nutrients are transferred from the mother to offspring by milk secretions generated in a specialized accessory gland called the milk gland. Disruption of the flow of nutrients into the developing larva, or the elimination of symbiotic bacteria both result in loss of host fecundity. The application has three goals. The first goal focuses on the transfer of lipids from the fat body tissue to the milk gland and its regulation. It will identify and characterize the conserved peptide hormone/receptor system (adipokinetic hormone) responsible for regulating lipid mobilization in insects as well as the system responsible for the physical movement of lipids through the hemolymph (lipophorin/lipophorin receptor). The second goal focuses on the protein components of the milk secretion. It will identify novel milk proteins in silico and characterize the promoter and regulatory regions to understand the transcription factors responsible for milk gland/pregnancy specific expression patterns. The third goal focuses on the indispensable role of symbiotic bacteria in host reproductive processes. It will characterize the factors symbionts provide to facilitate host fecundity, analyze the expression patterns of host reproduction associated genes in symbiont-cured sterile flies. Collectively, the proposed studies will identify key elements required for tsetse reproductive processes. These elements stand to provide targets for tsetse specific vector control strategies for use in the prevention of trypanosomiasis.

Public Health Relevance

This proposal will identify molecular targets in the tsetse fly reproductive system. These targets can be used to develop novel tsetse specific chemicals and/or strategies to disrupt tsetse reproduction. Disruption of tsetse reproduction would be an effective way to reduce or eliminate fly populations resulting in the prevention of trypanosome transmission to humans and livestock.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-IDM-B (02))
Program Officer
Costero, Adriana
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Yale University
Public Health & Prev Medicine
Schools of Medicine
New Haven
United States
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Attardo, Geoffrey M; Benoit, Joshua B; Michalkova, Veronika et al. (2014) The homeodomain protein ladybird late regulates synthesis of milk proteins during pregnancy in the tsetse fly (Glossina morsitans). PLoS Negl Trop Dis 8:e2645
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
Michalkova, Veronika; Benoit, Joshua B; Attardo, Geoffrey M et al. (2014) Amelioration of reproduction-associated oxidative stress in a viviparous insect is critical to prevent reproductive senescence. PLoS One 9:e87554
Benoit, Joshua B; Attardo, Geoffrey M; Michalkova, Veronika et al. (2014) A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients. PLoS Genet 10:e1003874
Benoit, Joshua B; Hansen, Immo A; Attardo, Geoffrey M et al. (2014) Aquaporins are critical for provision of water during lactation and intrauterine progeny hydration to maintain tsetse fly reproductive success. PLoS Negl Trop Dis 8:e2517
Michalkova, Veronika; Benoit, Joshua B; Weiss, Brian L et al. (2014) Vitamin B6 generated by obligate symbionts is critical for maintaining proline homeostasis and fecundity in tsetse flies. Appl Environ Microbiol 80:5844-53
Baumann, Aaron A; Benoit, Joshua B; Michalkova, Veronika et al. (2013) Juvenile hormone and insulin suppress lipolysis between periods of lactation during tsetse fly pregnancy. Mol Cell Endocrinol 372:30-41
Attardo, Geoffrey M; Benoit, Joshua B; Michalkova, Veronika et al. (2012) Analysis of lipolysis underlying lactation in the tsetse fly, Glossina morsitans. Insect Biochem Mol Biol 42:360-70
Benoit, Joshua B; Attardo, Geoffrey M; Michalkova, Veronika et al. (2012) Sphingomyelinase activity in mother's milk is essential for juvenile development: a case from lactating tsetse flies. Biol Reprod 87:17, 1-10

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