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ANR funded project

(DS0504) 2016
Projet DEMETER

Bio-olfacticides: More Food and less pesticides in insect control

Context:
Noctuid moths represent an important group of insects that includes the most devastating pests on the planet. As olfaction underlies several of their behaviours that are critical for crop aggression - including reproduction, host selection and oviposition - this sensory modality appears as an attractive target for the development of innovative strategies to reduce the negative impact of these pests.
At the molecular level, the key actors involved in the recognition of chemical signals are the olfactory receptors (ORs), thus they appear as the best targets for the rational design of selective “bio-olfacticides”, molecules able to modify the OR response and thus the corresponding behavior. The nature of insect ORs provides interesting opportunities: 1) they are completely different from vertebrate ORs, allowing targeted and safe actions; 2) they are highly divergent between insects, allowing to act in a selective way to preserve beneficial insects; 3) they present a 7-transmembrane domain structure, similar to that of G-protein coupled receptors (GPCRs) on which pharmacologic know-how is well developed, for the design of therapeutic drugs (i.e. agonists/antagonists interfering with the binding site and thus activating/inhibiting the cellular response).

Objectives:
In this context, we propose to characterize ligands of the ORs of the noctuid moth Spodoptera littoralis, a model species in agronomy for which we have identified a large array of ORs, thanks to a previous project funded by ANR. Its genome we are currently assembling will complete this repertoire. We propose to set up an innovative automatized high-throughput functional screening approach to identify a vast array of ligand-receptor couples (for the first time in a crop pest). This breakthrough in the field of molecular bases of olfaction in insects outside Diptera will identify ORs involved in key behaviors (reproduction, oviposition, attraction, repellence) to target in the frame of crop pest protection. Ligand-based and receptor-based molecular modelling approaches will be used to design in silico potential agonists/antagonists/blockers (the “bio-olfacticides”). Their effects on the OR responses and in fine the behaviour of pest insects will be tested.

Methodology and expected results:
Classical bioinformatics tools associated with manual curation will be used to define full length OR gene models in the genome. The characterization of ligands (or deorphanization) for the ORs identified in S. littoralis will be performed in vitro via their expression in Xenopus oocytes coupled to two-electrode voltage clamp electrophysiology. We will benefit from a high throughput (HT) technology designed for molecular pharmacology studies on mammalian GPCRs, which allows screening of a very large array of natural and synthetic ligands. Sensitivity, specificity and response dynamic of the ORs will be assessed. The response parameters obtained will define the first “odor space” of a crop pest, which will be compared to the two odor spaces established previously in two model insects (Drosophila and the mosquito Anopheles gambiae). Molecular modelling coupled to chemoinformatics will be used to predict potential bio-olfacticides for interesting ORs. The efficiency of these bio-olfacticides will be further tested at the molecular (OR) level using the HT screening platform, at the neuron level using electroantennography and at the behavioural level in the lab using larval (servosphere) and adult (wind tunnel) dedicated assays. More than a proof-of-concept to validate bio-olfacticide efficiency on insect behaviour, this project will propose active molecules to improve crop production and reduce pesticide use, in a context of food safety and environment protection.

Partners

CRB Xénope centre de ressources biologiques xénope

iEES-Paris Institut d'écologie et des sciences de l'environnement de Paris

UNS/ICN Université de Nice Sophia Antipolis - Institut de Chimie de Nice

ANR grant: 591 205 euros
Beginning and duration: janvier 2017 - 48 mois

 

ANR Programme: (DS0504) 2016

Project ID: ANR-16-CE21-0002

Project coordinator:
Madame Emmanuelle Jacquin-Joly (Institut d'écologie et des sciences de l'environnement de Paris)

 

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The project coordinator is the author of this abstract and is therefore responsible for the content of the summary. The ANR disclaims all responsibility in connection with its content.