Engineering Threshold-Based Selection Systems
Pedone, K. H.; Gonzalez-Perez, V.; Leopold, L. E.; Der, C. J.; Cox, A. D.; Ahmed, S.; Reiner, D. J.
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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 C. 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.
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