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Completed
RNAi: a nucleic acid-based immune system in insects
FunderNetherlands Organisation for Scientific Research (NWO)
Duration01 Jan 2009 - 07 Jul 2014
Project code864.08.003
Open Access mandatePublications: NoResearch data: No
Identifiers
Project timeline100%
Description
Background: Antiviral immunity in vertebrates depends on a rapid non-specific innate response, and an adaptive response that enhances viral clearance and protects from re-infection through the establishment of immunological memory. In contrast, non-vertebrate animals lack these classical protein-based immune responses, yet are capable of effectively clearing viral infections. This suggests that invertebrates depend on alternative mechanisms for antiviral defense. Previous research and preliminary observations: RNAi is a mechanism for specific gene silencing triggered by double stranded RNA (dsRNA). Recently, we demonstrated that RNA interference (RNAi) mediates antiviral defense in insects. Furthermore, we identified a novel pathway for cellular uptake of dsRNA that feeds into a productive RNAi response. Preliminary data suggest that this mechanism for dsRNA uptake is involved in antiviral immunity. Aim: I will further explore the mechanism and function of RNAi as a nucleic acid-based immune system in the model organism Drosophila melanogaster. Furthermore, I will analyze the role of dsRNA uptake in antiviral immunity, and study whether RNAi provides systemic, adaptive, sequence specific immunity. Approach: I will establish an infection model in which both virus (Drosphila C virus) and its natural host (Drosophila melanogaster) are amenable to genetic manipulation, one of the central challenges of modern virology. The combination of classical virology, molecular biology and genetics provides an extremely powerful model for our understanding of virus-host interactions, including RNAi, at the molecular level. Relevance: My proposal will provide insight in the molecular mechanism of RNAi and its in vivo function. Moreover, it will establish whether RNAi acts as a systemic adaptive immune response in insects. This exciting possibility will challenge current conventions that sequence specific adaptive immunity is an exclusive property of vertebrate immune responses.
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Background: Antiviral immunity in vertebrates depends on a rapid non-specific innate response, and an adaptive response that enhances viral clearance and protects from re-infection through the establishment of immunological memory. In contrast, non-vertebrate animals lack these classical protein-based immune responses, yet are capable of effectively clearing viral infections. This suggests that invertebrates depend on alternative mechanisms for antiviral defense. Previous research and preliminary observations: RNAi is a mechanism for specific gene silencing triggered by double stranded RNA (dsRNA). Recently, we demonstrated that RNA interference (RNAi) mediates antiviral defense in insects. Furthermore, we identified a novel pathway for cellular uptake of dsRNA that feeds into a productive RNAi response. Preliminary data suggest that this mechanism for dsRNA uptake is involved in antiviral immunity. Aim: I will further explore the mechanism and function of RNAi as a nucleic acid-based immune system in the model organism Drosophila melanogaster. Furthermore, I will analyze the role of dsRNA uptake in antiviral immunity, and study whether RNAi provides systemic, adaptive, sequence specific immunity. Approach: I will establish an infection model in which both virus (Drosphila C virus) and its natural host (Drosophila melanogaster) are amenable to genetic manipulation, one of the central challenges of modern virology. The combination of classical virology, molecular biology and genetics provides an extremely powerful model for our understanding of virus-host interactions, including RNAi, at the molecular level. Relevance: My proposal will provide insight in the molecular mechanism of RNAi and its in vivo function. Moreover, it will establish whether RNAi acts as a systemic adaptive immune response in insects. This exciting possibility will challenge current conventions that sequence specific adaptive immunity is an exclusive property of vertebrate immune responses.
