Advanced Research on the 3D structure of Mosquito Odorant Receptor coreceptor

Mission of the project

The main 3D-ORco’s goal is to obtain a deep understanding of the rules underlying the recognition of odorant molecules by the universal component of the insects’ olfaction system, the 7-transmembrane Odorant Receptor coreceptor (ORco), which is highly conserved across insect taxa including both disease vectors and agricultural pests. Most importantly, the 3D-ORco project will pave the way for the discovery, by ORco-structure-based approaches, of multiple new and effective disruptors of host seeking behavior to be employed in the effort to reduce the spread of insect-transmitted infectious diseases as well as control insects of agricultural importance.

A description of the 3D-ORco project and why it matters

The research project “Advanced Research on the 3D Structure of the Mosquito Odorant Receptor Coreceptor (3D-ORCO)” which is coordinated by the National Hellenic Research Foundation and Dr. Spyros Zographos, on behalf of the Institute of Chemical Biology (ICB/NHRF), was among the 22 Category II proposals in the area of “Life Sciences - Medical and Health Sciences”, funded by the Hellenic Foundation for Research and Innovation H.F.R.I. (ELIDEK) in the framework of the "1st Call for proposals for research projects for the support of Faculty members and Researchers working in the Greek Universities and Research Centers and the procurement of strategic research equipment.

The 3-years project 3D-ORco will be implemented in the Institute of Chemical Biology (ICB/NHRF) in collaboration with NCSR "Demokritos", the Greek Pasteur Institute, the University of Dublin and the University of Helsinki.

The project aims at the biochemical, molecular, functional and structural characterization of the 7-transmembrane Odorant Receptor coreceptor (ORco) of the mosquito Anopheles gambiae, applying the most up-to-date methodology and cutting-edge technology, including Nanodisk technology, Robotic high-throughput in meso crystallogenesis, Micro- and serial-crystallography using synchrotron radiation and high resolution cryo-Electron Microscopy.

Mosquitoes are the primary transmitters of multiple parasites and viruses that cause malaria, dengue fever, West Nile encephalitis, microcephaly in newborn infants due to Zika virus and many other serious and often fatal diseases.

The ultimate goal of the project is to reduce the spread of infectious diseases by inhibiting the ability of mosquitoes to locate a human host: Hematophagous female mosquitoes locate their human hosts by sensing certain volatile compounds emitted by humans. If we could succeed to disrupt this procedure, then disease vectors would lose their ability to orient themselves towards their human hosts, obtain a blood meal and transmit infectious virus and parasites in the process.

The results to be obtained from the successful implementation of the 3D-ORco project, in addition to being of great importance to public health, could be further exploited for the development of ecologically-smart methods for the control of agricultural and farm livestock insect pests, which represent primary factors leading to reduced production of major crops and increased losses of farm animals. Therefore, 3D-ORco could have a major economic impact on the agricultural and livestock raising sectors.


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