Presentation Title

Rational Design of New Larval Attractants to Control Mosquito-Borne Diseases

Faculty Mentor

Spiros Dimitratos

Start Date

17-11-2018 8:30 AM

End Date

17-11-2018 10:30 AM

Location

CREVELING 67

Session

POSTER 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Mosquito-borne diseases including Zika, dengue fever and malaria continue to threaten public health, and their persistence reflects the limitations of existing mosquito control strategies. Although several mosquito control measures focus on adult populations, few technologies are directed against larvae, and mosquito eradication campaigns worldwide would benefit from new, more effective larval control tools. Our goal is to develop species-specific attractants capable of luring mosquito larvae to kill stations. Our laboratory has validated a novel method to rapidly discover new insect attractants. This approach employs rational design and targets protein components of the insect chemosensory pathways that regulate behavior. In mosquitoes, odorant binding proteins (OBPs) facilitate the detection of odor molecules in the environment and thus control crucial behaviors such as foraging and feeding. OBPs are therefore ideal targets for developing new, species-specific behavioral modifiers. We have cloned the gene encoding OBP1, a protein known to control mosquito behavior, from the mosquito, Culex quinquefasciatus. We used recombinantly expressed C. quinquefasciatus OBP1 protein in a proprietary, high throughput, fluorescence-based assay to screen combinatorial chemical and natural compound libraries for binding partners in vitro and have isolated numerous leads, including 54 synthetic molecules and 14 natural compounds. These molecules are now being assessed for their ability to attract living mosquito larvae in small-scale behavioral tests. Molecules capable of luring larvae will be tested in field trials in order to identify baits for low-cost larval bait-and-kill stations. In parallel we are isolating lead molecules capable of binding OBP1 from Aedes aegypti. Attractants isolated in this manner can then be tested on the larvae of other harmful mosquito species, including Anopheles gambiae. Moreover, the platform technologies used in this study are applicable to the efficient isolation of behavioral modifiers to control a variety of other harmful insect species.

Summary of research results to be presented

Our work focuses on controlling the larvae of harmful mosquito species by generating a highly effective lure that will be incorporated in targeted bait-and-kill stations. Our approach utilizes rational design. We have cloned the gene encoding OBP1, an insect chemosensory protein known to control behavior, from the mosquito, Culex quinquefasciatus. We used recombinantly expressed C. quinquefasciatus OBP1 protein to screen a combinatorial chemical library for binding partners and isolated 54 molecules that interact with the protein’s binding pocket. We also screened a natural compound library containing compounds derived from plant extracts and isolated 14 natural compounds that interact with the protein’s binding pocket. Protein binding studies were performed using a validated, fluorescence-based high throughput assay developed in our laboratory that has successfully identified novel behavioral modifier molecules for a variety of insect species. The lead molecules identified in our assay are now being tested for their ability to attract living C. quinquefasciatus larvae in small-scale behavioral tests that we are performing in the laboratory. In parallel we are isolating lead molecules capable of binding OBP1 from Aedes aegypti, and are planning to expand our approach to Anopheles gambiae. The platform technologies employed are versatile and can be used to rapidly identify behavioral modifiers to control a variety of harmful insect species. Our research results include data regarding expression and purification of the 18 kD OBP protein, fluorescent assay design and implementation, assay results including chemical characteristics of the compounds isolated, and a discussion of the enabling platform technologies.

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Nov 17th, 8:30 AM Nov 17th, 10:30 AM

Rational Design of New Larval Attractants to Control Mosquito-Borne Diseases

CREVELING 67

Mosquito-borne diseases including Zika, dengue fever and malaria continue to threaten public health, and their persistence reflects the limitations of existing mosquito control strategies. Although several mosquito control measures focus on adult populations, few technologies are directed against larvae, and mosquito eradication campaigns worldwide would benefit from new, more effective larval control tools. Our goal is to develop species-specific attractants capable of luring mosquito larvae to kill stations. Our laboratory has validated a novel method to rapidly discover new insect attractants. This approach employs rational design and targets protein components of the insect chemosensory pathways that regulate behavior. In mosquitoes, odorant binding proteins (OBPs) facilitate the detection of odor molecules in the environment and thus control crucial behaviors such as foraging and feeding. OBPs are therefore ideal targets for developing new, species-specific behavioral modifiers. We have cloned the gene encoding OBP1, a protein known to control mosquito behavior, from the mosquito, Culex quinquefasciatus. We used recombinantly expressed C. quinquefasciatus OBP1 protein in a proprietary, high throughput, fluorescence-based assay to screen combinatorial chemical and natural compound libraries for binding partners in vitro and have isolated numerous leads, including 54 synthetic molecules and 14 natural compounds. These molecules are now being assessed for their ability to attract living mosquito larvae in small-scale behavioral tests. Molecules capable of luring larvae will be tested in field trials in order to identify baits for low-cost larval bait-and-kill stations. In parallel we are isolating lead molecules capable of binding OBP1 from Aedes aegypti. Attractants isolated in this manner can then be tested on the larvae of other harmful mosquito species, including Anopheles gambiae. Moreover, the platform technologies used in this study are applicable to the efficient isolation of behavioral modifiers to control a variety of other harmful insect species.