THIS RESEARCH ALIGNS WITH AREA 5E OF THE BRAG RFA, MODELING APPROACHES TO UNDERSTAND THE IMPACT OF GENETIC ENGINEERING FOR POPULATION SUPPRESSION OR ALTERATION (GENE DRIVE, RELEASE OF INSECT CARRY DOMINANT LETHAL, ETC.) ON TARGET POPULATIONS OR NON-TARGET SPECIES THAT INTERACT WITH THE TARGETED SPECIES, ESPECIALLY WHEN INCORPORATING BIOLOGICALLY REALISTIC PARAMETERS (E.G. OF RESISTANCE EVOLUTION, NUMBERS OF INDIVIDUALS RELEASED, ETC.)OUR GOALS ARE (1) TO ASSESS THE RISKS OF GENOME EDITING TECHNOLOGIES, SUCH AS CRISPR-CAS9, WHEN USED TO MAKE GENE DRIVES TO SUPPRESS POPULATIONS OF CROP PESTS; (2) TO ASSESS THE EFFECT OF GENETIC BACKGROUND ON THE SPREAD OF GENE DRIVES; AND, TO IDENTIFY AND CHARACTERIZE DRIVE RESISTANT MUTATIONS PRE-EXISTING IN WILD POPULATIONS OR CREATED BY FEATURES OF CRISPR/CAS 9 ITSELF ; AND, (3) TO INCORPORATE OUR EXPERIMENTAL FINDINGS INTO MODELS OF GENE DRIVE.WE PROPOSE TO CONSTRUCT GENE DRIVES AND INTRODUCE THEM INTO POPULATIONS OF THE FLOUR BEETLE TRIBOLIUM CASTANEUM, A STORAGE GRAIN PEST. WE WILL IDENTIFY KEY FACTORS GOVERNING THE SPREAD OF GENE DRIVES IN WILD POPULATIONS AND IN GENETICALLY SUBDIVIDED POPULATIONS COMPARABLE TO REGIONAL AGRICULTURAL FIELDS. WE WILL DEVELOP GENE DRIVES ON GENETIC BACKGROUNDS SIMILAR TO AND DIVERGENT FROM THE LABORATORY STRAINS AND CHARACTERIZE THE GENETIC FEATURES OF POPULATIONS THAT REDUCE DRIVE EFFICIENCY. OUR RESULTS AND METHODS WILL INFORM THE DEVELOPMENT OF GUIDELINES FOR REGULATORY AGENCIES CHARGED WITH EVALUATING THE LIKELIHOOD OF SUCCESS OF PROPOSED DRIVE RELEASES.WE PROPOSE TO ASSESS THE BIOLOGICAL RISKS ASSOCIATED WITH THE PROPOSED USE OF GENE DRIVES BASED ON CRISPR-CAS9 GENOME EDITING TECHNOLOGY TO CONTROL CROP PESTS. MOREOVER, WE PROPOSE TO CONSTRUCT AND EVALUATE THE EFFICACY OF DRIVE REVERSAL SAFEGUARDS FOR CONTROLLING OR STOPPING THE SPREAD OF ARTIFICIAL GENE DRIVES AND PREVENTING FUTURE SPREAD OF A DRIVE TARGETING THE SAME REGION WITHIN A GENE OF INTEREST.