Project Number: 2030-42000-054-005-N
Project Type: Non-Funded Cooperative Agreement
Start Date: Jan 3, 2022
End Date: Dec 31, 2025
Israel and California share similar geography, agriculture, and insect pests, and in both countries developing new approaches for suppressing pests while protecting mass-reared insects providing bio-control or pollination services is urgently needed. An attractive novel approach is to modulate insect immune responses and, consequently, their ability to handle microbial infections. Herein, we will develop this concept and target principal components of the insect immune system using environmentally safe, previously approved natural products. This cooperation aims to apply the concept of host-directed therapeutics for modulating the insect immune system and affecting their ability to handle microbial infections. This will be achieved by identifying immuno-suppressing or -protecting molecules from a library of previously approved natural products and validating their activity in a major agricultural pest. Our ultimate goal is to apply this approach to control pests and improve the mass-rearing of beneficial insects. The deliverables of this project are: (1) the first of the kind library of approved natural products, which could be shared with ARS centers and the wider research community; (2) highly effective, broad-spectrum, safe, and commercially viable natural compounds that suppress the immunity of Drosophila and other insect pests; (3) identify new regulatory proteins which can be chemically targeted in order to disrupt the insect immune system; (3) natural products that increase the immunity of pollinators and bio-control insects against insecticidal microbes; (4) method of use patents to thwart insect pests and protect pollinators and bio-control insects; and (5) joint publications in peer-reviewed scientific journals.
This will be achieved by screening a library of approved natural products for immuno-active effects in Drosophila melanogaster - a model organism for immunity and genetic studies in insects. Additionally, we will determine insect immune pathways and proteins targeted by identified natural product hits using specific Drosophila mutant strains. Since immunity pathways are well conserved in insects, we will confirm our findings in laboratory bioassays with the Mediterranean fruit fly (Ceratitis capitata, Medfly) – a major agricultural pest of worldwide importance. Concurrently, identified immune-activating compounds will be used to enhance the resistance of mass-reared male Medflies, used in sterile insect technique control operations, to microbial infections prevailing in rearing facilities. Additionally, the effect of identified immuno-suppressing compounds on the survival, immune response, and gut microbiome of wild Medflies will be determined. We expect that targeting insect-microbe associations by natural immune-modulators as proposed herein will advance novel avenues for pest control and provide tools to improve the mass-rearing of beneficial insects. Overall, the work plan will consist of three steps: screen a library of approved natural products for molecules having immuno-active effects in infected Drosophila flies, develop immune-suppressing natural products for insect pests, and develop immune-activating natural products for bio-control insects. The proposed systematic repurposing of natural products is a novel approach that will undoubtingly find its application in other drug discovery fields. Moreover, the concept of modulating insect immunity, which will be further developed herein, can be extended to other agricultural pests, for controlling infectious diseases transmission by insects, in mass-rearing applications and environmental /ecological sciences involving insects.