Presentation Title

Using Comparative Genomics To Control The Spread Of Arboviruses And Malaria

Faculty Mentor

Spiros D. Dimitratos

Start Date

23-11-2019 8:45 AM

End Date

23-11-2019 9:30 AM

Location

92

Session

poster 2

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

In spite of advances in medicine and public health, malaria and other mosquito-borne diseases such as yellow fever, dengue, Zika and chikungunya not only persist, but in some cases are spreading. Genetically modified mosquitoes, safer insecticides and vaccines are all under development, but current control strategies have not eradicated mosquito populations in affected areas. Moreover, climate change threatens to expand the habitable zone for many harmful mosquito species. Our goal is to augment ongoing eradication campaigns with a series of novel larvicides that are specifically active against harmful mosquitoes. To do so we have utilized a rational design approach that targets an odorant-binding protein, OBP1, critical to mosquito olfaction. Since OBPs control crucial behaviors such as feeding, interfering with their function by introducing a new ligand has the potential to alter mosquito behavior. We have therefore expressed and purified recombinant mosquito OBPs and used these proteins as targets for binding partners in a proprietary high throughput assay. Our laboratory has screened a combinatorial chemical library and a natural compound collection for small molecules that can bind orthologs of OBP1 from Aedes aegypti and Culex quinquefasciatus. These screens have identified 46 synthetic molecules and 13 natural compounds that bind to A. aegypti OBP1; we have also isolated 54 synthetic molecules and 14 natural compounds that bind to C. quinquefasciatus OBP1. Leads identified in this manner are being evaluated in behavioral assays that test for molecules capable of stimulating larval feeding behavior. Successful leads will form the basis of next-generation, mosquito-specific lures that can be incorporated into bait-and-kill stations to limit larval populations. These lures will help prevent disease transmission by interrupting the vector life cycle at an earlier stage and in a more targeted manner than many existing techniques.

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Nov 23rd, 8:45 AM Nov 23rd, 9:30 AM

Using Comparative Genomics To Control The Spread Of Arboviruses And Malaria

92

In spite of advances in medicine and public health, malaria and other mosquito-borne diseases such as yellow fever, dengue, Zika and chikungunya not only persist, but in some cases are spreading. Genetically modified mosquitoes, safer insecticides and vaccines are all under development, but current control strategies have not eradicated mosquito populations in affected areas. Moreover, climate change threatens to expand the habitable zone for many harmful mosquito species. Our goal is to augment ongoing eradication campaigns with a series of novel larvicides that are specifically active against harmful mosquitoes. To do so we have utilized a rational design approach that targets an odorant-binding protein, OBP1, critical to mosquito olfaction. Since OBPs control crucial behaviors such as feeding, interfering with their function by introducing a new ligand has the potential to alter mosquito behavior. We have therefore expressed and purified recombinant mosquito OBPs and used these proteins as targets for binding partners in a proprietary high throughput assay. Our laboratory has screened a combinatorial chemical library and a natural compound collection for small molecules that can bind orthologs of OBP1 from Aedes aegypti and Culex quinquefasciatus. These screens have identified 46 synthetic molecules and 13 natural compounds that bind to A. aegypti OBP1; we have also isolated 54 synthetic molecules and 14 natural compounds that bind to C. quinquefasciatus OBP1. Leads identified in this manner are being evaluated in behavioral assays that test for molecules capable of stimulating larval feeding behavior. Successful leads will form the basis of next-generation, mosquito-specific lures that can be incorporated into bait-and-kill stations to limit larval populations. These lures will help prevent disease transmission by interrupting the vector life cycle at an earlier stage and in a more targeted manner than many existing techniques.