Engineering threshold-based selection systems.
Katherine H PedoneVanessa González-PérezLuciana E LeopoldNeal R RasmussenChanning J DerAdrienne D CoxShawn AhmedDavid J ReinerPublished in: G3 (Bethesda, Md.) (2021)
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.