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ENAROMaTIC


European Network for Advanced Research on Olfaction for Malaria Transmitting Insect Control
 
 
Framework programme:
 7
Contract/Grant agreement number:
222927
EC contribution:
2,500,000 €
Duration:
48 months
Funding scheme:
Collaborative Project
Starting date:
01/12/2008
Project website:
http://www.enaromatic.org
 
 

Keywords: malaria control, mosquito vector, Anopheles gambiae, odorant binding proteins, odorant receptors, odour ligands, ligand mimetics, high throughput screening assays, ligand binding modelling

Background

The inability of health authorities to control the spread of malaria in places where the disease is endemic is due to ineffectiveness of existing drug treatments, lack of effective vaccines and resistance of the mosquito vector to insecticides.

Aims and expected results

In this project, the specificity of odour recognition by Anopheles gambiae odorant binding proteins (OBPs) and odorant receptors (ORs) is being investigated and correlated with quantifiable physiological and behavioural responses. For olfactory proteins involved in the detection of human hosts, OBP-OR pairs residing in common antennal olfactory sensilla and recognising common host-related ligands will be identified using high-throughput screening assays employing purified recombinant OBPs, reconstituted insect cell-based OR expression platforms and libraries of synthetic and natural compounds. OBP crystal-based structure determination and modelling of ligand fitting into OBP ligand-binding pockets will also be carried out in order to design ligand mimetics with improved binding and functional properties.

The effectiveness of newly identified ligands will be established by in vivo electrophysiological and behavioural assays on female mosquitoes. Finally, lead compounds acting as disruptors of normal olfactory and host seeking mosquito behaviour but lacking mammalian cell toxicity will be tested in model sites in Africa where A. gambiae (and malaria) is endemic, to determine efficacy characteristics under conditions that simulate the sites of possible application of newly developed products. This approach to dissecting mosquito vector olfactory function should yield results that will enhance our understanding of the mechanisms that control odour recognition in mosquitoes.

The ultimate goal of the project is to identify multiple natural or synthetic compounds capable of interfering with the olfactory function of mosquitoes by causing olfactory disorientation and/or acting as strong odour-based mosquito repellents or attractants that will effectively antagonise those emitted by the human skin and will be safe for human application. Besides the anticipated reduction in the rate of malaria parasite spread in the human target population due to the reduction in human blood-feeding frequency, a concomitant reduction in the size of the mosquito populations is also expected to occur due to the inability of blood-unfed female mosquitoes to complete the maturation of their reproductive system. The identification of multiple disruptors of host seeking behaviour of female mosquitoes will provide multiple new and effective tools to be employed in the effort to reduce the incidence of contact between the human host and the insect vector carrying the malaria parasite. Last but not least, the outcome of the proposed studies should serve as a paradigm for analogous efforts aimed at a reduction in disease transmission by other disease-carrying insect vectors.

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