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Insects make up a significant component of the global biosphere with many beneficial roles. Unfortunately insects also have catastrophic impacts as agriculture pests and vectors of medical and veterinary disease

From 2005-2015 we were privileged to participate in a broad international network of five laboratories  selected for a Bill and Melinda Gates Foundation Grand Challenge In Global Health (GCGH) grant to target Anopheline odorant receptors (ORs) to identify a new generation of mosquito repellents and attractants (read more about our GCGH project). Our premise was to search for Behaviorally Disruptive Compounds (BDOCs) that would block (antagonize) or active (agonize) mosquito ORs that would be useful in “push-pull” vector control strategies.

The project took this on using several approaches, one of the efforts here at Vanderbilt involved high-throughput small molecule screens of the Vanderbilt Institute for Chemical Biology chemical library with HEK cells expressing different Anopheline OR/Orco complexes for which we had already identified cognate odorant ligands (see Rinker etal. 2012 from our Publications). In this way we hoped to identify small molecules that could agonize, antagonize or potentiate the AgOR/Orco responses.  Remarkably, those efforts were successful  by discovering VUAA1 a novel synthetic with the unique ability to allosterically activate all insect Orco co-receptors. (see Jones et. al 2011 from our Publications).

Building upon that lead, Vanderbilt synthetic chemists explored the structure-activity relationships around VUAA1 to identify other VUAA’s that were more powerful Orco agonists (VUAA2, 3 or 4) as well as a suite of analogs that were Orco antagonists that showed significantly higher potency than DEET and other actives behavioral assays using mosquito larvae (see Taylor et. al 2012 and Romaine etal 2014 from our Publications).

In light of the extraordinary conservation of the Orco co-receptor across practically all insects, VUAA agonists have the unique ability to broadly hyper-activate all OR/Orco complexes expressed in all odorant receptor neurons in all insects. This creates an opportunity to create a novel suite of insect excito-repellents that actively repel insects by over-stimulation of their olfactory systems.  What are excito-repellents? Imagine your response to someone shouting at you at the top of their lungs….that’s Excito-Repellency!

Together with the Vanderbilt Center for Commercialization and Technology Transfer (CTTC)  we have applied for and been awarded a range of VUAA-based patents (see our Patents). We are currently working with several private sector partners towards the development of a range of products that use VUAA-based active ingredients (VUAIs) as direct and spatial insect Excito-Repellents against agricultural pests, disease vectors and nuisance insects.