%0 Journal Article %T Engineering threshold-based selection systems. %A Pedone KH %A González-Pérez V %A Leopold LE %A Rasmussen NR %A Der CJ %A Cox AD %A Ahmed S %A Reiner DJ %J G3 (Bethesda) %V 11 %N 9 %D 09 2021 6 %M 34544135 %F 3.542 %R 10.1093/g3journal/jkab234 %X Using model organisms to identify novel therapeutic targets is frequently constrained by pre-existing genetic toolkits. To expedite positive selection for identification of novel downstream effectors, we engineered conditional expression of activated CED-10/Rac to disrupt Caenorhabditis elegans embryonic morphogenesis, titrated to 100% lethality. The strategy of engineering thresholds for positive selection using experimental animals was validated with pharmacological and genetic suppression and is generalizable to diverse molecular processes and experimental systems.