European Network for Advanced Research on Olfaction for MalariaTransmitting Insect Control

 

Acronym: ENAROMaTIC
Title: European Network for Advanced Research on Olfaction for MalariaTransmitting Insect Control
Status: Active
Funding Organization: European Union

Health-222927

NCSR D Role: Coordinator
Leader in charge: K. Iatrou
Start Date: 1/12/2008
Duration: 48 months
Project Website: www.enaromatic.org
Summary  The specificity of odour recognition by odorant binding proteins (OBPs) and odorant receptors (ORs) of the mosquito malaria vector Anopheles gambiae is investigated and correlated with quantifiable physiological and behavioural responses. For olfactory proteins involved in the detection of human hosts, OBPs and ORs 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 vivoelectrophysiological 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.

 The ultimate goal of the project is to identify multiple natural or synthetic compounds capable of interfering with the olfactory function of mosquitoes causing olfactory disorientation and 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 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. 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.