IRP REPEL between the coordinator’s home laboratory: UMR7261 – Institut de Recherche sur la Biologie de l’Insecte – IRBI (CNRS / University of Tours) and Institut de Biodiversité et Biologie Expérimentale et Appliquée (IBBEA), CONICET – University of Buenos Aires
The work program consists of :
1) Evaluate the response of mosquito taste receptors to natural substances with a bitter taste for humans and other animals, including insects such as the Drosophila fly, to establish the type of molecules likely to be detected by mosquitoes.
2) evaluate the effectiveness of such molecules as next-generation biorepellents.
3) evaluate the physiological and behavioral effects caused by contact with and possible ingestion of taste repellents, using energy metabolism measurements and learning tests.
4) determine the personal protection potential of the selected substances by carrying out the “arm in the cage” tests recommended by the World Health Organization, but modified to avoid any exposure of the experimenter to stings.
5) compare repellent efficacy with that of commercial reference products (e.g. DEET, IR3535 and others).
Complementary teams :
The three partners have internationally recognized skills that complement each other perfectly.
IRBI and the project leader, C. Lazzari, have extensive experience in the analysis of physiology, sensory ecology and cognition in various disease-vector arthropods, including mosquitoes, as well as in the study of repellents. The team’s approach is fundamentally based on physiological and behavioral analysis under perfectly controlled conditions. IRBI provides an ideal setting with infrastructures for breeding, experimentation and platforms (chemical, molecular) adapted to insect research.
R. Barrozo’s laboratory at the Institute of Biodiversity and Experimental and Applied Biology has been working for many years on gustation in disease-vector insects, using a molecular, physiological and behavioral approach. The laboratory is part of Argentina’s largest and most important scientific training and research structure, the Faculty of Exact and Natural Sciences of the University of Buenos Aires and CONICET.
David Carrasco’s laboratory (MIVEGEC) specializes in the chemical ecology of mosquitoes, in particular Anopheles spp. and the detection of insecticides and repellents by the mosquito sensory system (INDeed project – ANR). MIVEGEC is a major center for research into the biology of insect vectors and the fight against the transmission of vector-borne diseases around the world.
The work of the three partners will be organized as follows:
- IRBI: behavioral tests of contact repulsion and blood feeding in Aedes aegypti (the world’s most cosmopolitan vector) and Aedes albopictus (tiger mosquito, one of the world’s most invasive species) under controlled conditions. Real-time metabolic measurements (O2 consumption and CO2 production) in response to bitter substances, to determine any deleterious effects at physiological level.
- IBBEA-CONICET: analysis of taste function at morphological, physiological and molecular levels in mosquitoes, in particular its involvement in the detection of bitter substances. Methodology includes electrophysiology of contact chemoreceptors (tip-recording), transcriptomic analyses, RNAi and others.
D. Carrasco – MIVEGEC: in the context of IRP REPEL, the partner will be in charge of electrophysiological (single sensilium recording – SSR) and behavioral studies on malaria vector Anopheles.
The three partners will focus on screening and testing the repellency of candidate substances for use as birational contact repellents.
Criteria such as repellent efficacy, ease of production, cost and toxicity to humans and the environment will be given priority in this research. The REPEL IRP aims to provide the basis for the formulation of the next generation of repellents for personal protection against disease transmission.
Background to the cooperation and existing relations :
The present proposal represents the natural continuation of two collaborative projects between France and Argentina, one funded by the ECOS-Sud program obtained in January 2020 and the other a PICT-Raíces project fully funded by the Argentine Ministry of Research (MINCYT). Both projects are led by REPEL’s French (C. Lazzari) and Argentinean (R. Barrozo) managers.
IRBI and the University of Buenos Aires have a long and productive history of scientific collaboration in the study of disease vector biology, marked by publications, research contracts, international training courses and co-supervision, including a cotutelle thesis to be defended in 2019.
The heads of the two countries (R. Barrozo and C. Lazzari) co-authored eight publications in international peer-reviewed journals (e.g. Chemical Senses, Journal of Comparative Physiology, Trends in Parasitology, Biological Rhythm Research, Journal of Insect Physiology).
The three partner laboratories have extensive experience, validated by publications, in studying the sensory biology of various disease vectors (mosquitoes, bedbugs) and repellents.
The two French teams have been collaborating for many years in Master’s-level training activities, participating in commissions, juries and more.
Expected project results :
We envisage the development of a new generation of repellents, operating on the gustatory system, for personal protection against disease vectors, respecting the environment in a “one-health” approach. Secondly, we hope that our innovative approach will inspire a more rational and effective way of conducting repellent research than the simple trial and error of today.
More specifically, we expect the following results from REPEL:
1) Identification and morphological and functional characterization of mosquito taste structures, potentially involved in the detection of bitter substances.
2) Characterization of the effect of bitter-tasting substances on mosquito biting and feeding, in vitro (artificial feeding) and in vivo (cage test, WHO).
3) Determination of the physiological impact of contact and ingestion (in vitro) of low doses of deterrent substances, analyzing metabolic and survival consequences.
4) Selection of candidate substances, based on criteria of repellent efficacy, non-toxicity and ease of production, and determination of action time as a function of dose.
5) Determining the ability of mosquitoes to learn to avoid our repellents or to associate them with a host, in order to assess the extent to which individual experience can modify mosquitoes’ exposure behavior using new repellents.
Industrial prospects or expectations for the project :
REPEL is designed to give us the opportunity to establish industrial partnerships for the production and marketing of rational repellents.
Once the first validations of proven repellent substances acting on mosquitoes’ sense of taste have been obtained, we will launch an intellectual property protection process, followed by discussions with potentially interested industrial players.
Expected benefits of the collaboration for the French laboratory(ies) :
IRBI and MIVEGEC are very active players in disease vector research.
Their profiles and approaches are different, but highly complementary, and they are involved in training (teaching), research, evaluation and science management activities in this field.
REPEL will bring an international dimension, strengthening existing links and consolidating their scientific influence in South America, a region where the presence of IRD and CNRS will also be reinforced.
French laboratories will benefit from the skills of Argentinean colleagues and the transfer of their methodological know-how to France.
In addition, the collaboration will enable young people from both countries to be trained in issues that are at the heart of research at IRBI and MIVEGEC, such as the sensory ecology of vectors or the fight against the transmission of vector-borne diseases.
Contribution of French laboratory(ies) to the project :
The French laboratories will contribute their respective expertise in the physiology and sensory ecology of the mosquitoes targeted by the study, i.e. Aedes, the world’s most cosmopolitan vector, and Anopheles, the vector of malaria in vast regions of the world.
IRBI and MIVEGEC have the tools and experience to decipher fundamental aspects of the problem, such as the physiological basis of the response to repellents, as well as applied aspects, such as the quantitative evaluation of repellent efficacy, according to protocols validated by the World Health Organization.
Furthermore, field validation of repellents will be facilitated by access to sites where the species on which the studies will be carried out are abundant, such as southern France (Aedes albopictus) and African countries (Anopheles).
Contribution of foreign laboratory(ies) to the project :
The Argentine laboratory will contribute its expertise in taste perception in hematophages, as well as the tools needed to analyze the sensory basis of mosquito response to repellents.
As in the case of the French laboratories, field validation of repellents will be facilitated by access to sites where the species on which the studies will be carried out are abundant, in particular Aedes aegypti, which is very abundant in Argentina as in the south of France (Aedes albopictus) and African countries (Anopheles).
Identification of risks with regard to the PPST (Protection of the Nation’s Scientific and Technical Potential) and proposed measures to limit these risks
In the context of the PPST, the project is likely to produce information of commercial interest (new repellents) in the medium to long term. The researchers, laboratories and supervisory bodies involved in the consortium have experience in protecting intellectual property on discoveries. Laboratory notebooks drawn up according to CNRS standards will be set up, and each discovery likely to be of industrial interest will be shared with the supervisory bodies for protection.