> 550 MILLION POUNDS OF INSECTICIDES ARE USED ANNUALLY IN THE US, BUT OUR UNDERSTANDING OF THE POISONING PROCESSES IN INSECTS IS FAR FROM COMPLETE.OUR OVERALL GOAL IS TO CHARACTERIZE THE GENETIC VARIATION THAT CONTROLS THE VARIATION IN SENSITIVITY OF A NAÏVE (I.E. SUSCEPTIBLE) POPULATION TO INSECTICIDES AND IDENTIFY THE GENES INVOLVED IN THE POISONING PROCESS. WE WILL COMPLETE THREE OBJECTIVES:1- USING GENOME-WIDE ASSOCIATION STUDIES OF THE DROSOPHILA GENETIC REFERENCE PANEL (DGRP), WE WILL IDENTIFY ALLELES AND GENES RESPONSIBLE FOR VARIATION IN RESPONSE TO INSECTICIDE POISONING USING TWO INSECTICIDES TO WHICH THE SPECIES IS NAÏVE: CHLORANTRANILIPROLE AND BROFLANILIDE.2- USING TRANSCRIPTOMICS, WE WILL CHARACTERIZE THE GENE REGULATORY NETWORKS THAT CONTROL INDUCIBLE RESPONSES FOLLOWING EXPOSURE TO CHLORANTRANILIPROLE AND BROFLANILIDE. WE WILL EXAMINE THE TIME COURSE OF TRANSCRIPTIONAL RESPONSE TO EXPOSURE WITH THESE INSECTICIDES. WE WILL THEN EXPAND TO CHARACTERIZE DIFFERENCES BETWEEN LINES FROM THE DGRP PANEL WITH DIFFERENT SURVIVAL PHENOTYPE TO THE INSECTICIDES. THIS WILL IDENTIFY THE VARIANTS WITH ALTERED EXPRESSION AND GENES/GENE NETWORKS THAT CONTROL INSECTICIDE SENSITIVITY.3- WE WILL VALIDATE FUNCTIONALLY THE ROLE OF THE CANDIDATE GENES BY RNAI, NULL LINES AND/OR OVEREXPRESSION LINES, AND THE ROLE OF SELECT SNPS (FROM OBJECTIVES 1 AND 2) USING CRISPR ALLELE REPLACEMENT.OF NOTE, OBJECTIVE 1 AND 2 ARE COMPLEMENTARY AS THEY WILL GIVE US 2 UNBIASED APPROACHES TO IDENTIFY BOTH GENES THAT FUNCTIONALLY UNDERLIE SUSCEPTIBILITY TO INSECTICIDES AND GENES ASSOCIATED WITH THE RESPONSE TO INSECTICIDES.

Cornell University, Ithaca NY

Investigators