Although Drosophila melanogaster is a model system for the molecular genetics of innate immunity, virtually nothing is known about the life history and virulence strategies of its natural parasites. Parasitic wasps can infect Drosophila larvae at frequencies greater than 50% in natural populations, and are highly amenable to laboratory and field study. The Schlenke lab has developed a collection of 17 live wasp parasite strains of Drosophila, and robust protocols for extracting and manipulating the venom cocktails they use to thwart the host cellular encapsulation response mounted against their eggs. In this application, Schlenke proposes to use a joint transcriptomic and proteomic approach to identify the venom gland contents of 10 related wasp species that are highly successful infectors of D. melanogaster. He will then assay the effects of whole venom from each wasp species using two types of assays: First, he will assay the effects of venom on the structure and function of D. melanogaster hemocytes ex vivo. Second, he will assay encapsulation defects in vivo by injecting oil droplets into flies, which are readily melanotically encapsulated, mixed with venom fractions. For any immune suppressive effects that whole venom has, Schlenke will then identify venom fractions and individual venom proteins responsible for these characterized venom effects. Finally, Schlenke will use population genetic and molecular evolution approaches to uncover how venoms maintain virulence function in their co-evolutionary arms race with host immune systems. In sum, Schlenke hopes to develop the Drosophila-wasp system as a model for the study of eukaryotic host-pathogen interactions and for the evolution of parasite life histories.

Public Health Relevance

The purpose of this project is to understand how parasites suppress host immune responses; using the fruit fly Drosophila melanogaster and its natural parasitic wasps as a model host-parasite pair. This work will identify and functionally characterize the venom (virulence) proteins that wasps use to suppress conserved aspects of host innate immunity. By characterizing venom repertoires across a phylogeny of wasps; patterns of parasite virulence strategy evolution will be uncovered.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
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Singleton, Kentner L
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University of Arizona
Schools of Earth Sciences/Natur
United States
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Kacsoh, Balint Z; Bozler, Julianna; Schlenke, Todd A (2014) A role for nematocytes in the cellular immune response of the drosophilid Zaprionus indianus. Parasitology 141:697-715
Keebaugh, Erin S; Schlenke, Todd A (2014) Insights from natural host-parasite interactions: the Drosophila model. Dev Comp Immunol 42:111-23
Goecks, Jeremy; Mortimer, Nathan T; Mobley, James A et al. (2013) Integrative approach reveals composition of endoparasitoid wasp venoms. PLoS One 8:e64125
Mortimer, Nathan T; Goecks, Jeremy; Kacsoh, Balint Z et al. (2013) Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity. Proc Natl Acad Sci U S A 110:9427-32
Kacsoh, Balint Z; Lynch, Zachary R; Mortimer, Nathan T et al. (2013) Fruit flies medicate offspring after seeing parasites. Science 339:947-50
Milan, Neil F; Kacsoh, Balint Z; Schlenke, Todd A (2012) Alcohol consumption as self-medication against blood-borne parasites in the fruit fly. Curr Biol 22:488-93
Keebaugh, Erin S; Schlenke, Todd A (2012) Adaptive evolution of a novel Drosophila lectin induced by parasitic wasp attack. Mol Biol Evol 29:565-77
Lefevre, Thierry; de Roode, Jacobus C; Kacsoh, Balint Z et al. (2012) Defence strategies against a parasitoid wasp in Drosophila: fight or flight? Biol Lett 8:230-3
Kacsoh, Balint Z; Schlenke, Todd A (2012) High hemocyte load is associated with increased resistance against parasitoids in Drosophila suzukii, a relative of D. melanogaster. PLoS One 7:e34721
Mortimer, Nathan T; Kacsoh, Balint Z; Keebaugh, Erin S et al. (2012) Mgat1-dependent N-glycosylation of membrane components primes Drosophila melanogaster blood cells for the cellular encapsulation response. PLoS Pathog 8:e1002819