Revealing manduca sexta´s nicotine metabolism and its ecological consequences using plant mediated RNAi based reverse genetics Insects have developed a myriad of adaptations to live and evolve. Manduca sexta a specialist lepidopteran herbivore of Nicotiana attenuata has developed a remarkable adaptation to tolerate a toxic alkaloid ‘nicotine’ that it ingests from its host plant Nicotiana attenuata. The mechanism of nicotine tolerance in M. sexta larvae is not completely known. In this work I used a reverse genetics based approach to silence M. sexta’s genes involved nicotine tolerance to understand their role and ecological consequences of nicotine adaptation by this insect. Nicotine induced midgut based M. sexta CYP6B46 was silenced by plant mediated RNAi. Survivorship of CYP6B46 silenced M. sexta larvae was found to be lowered similar to that of low nicotine foliage feeding larvae in the field (Great Basin desert Utah). While investigating the reasons for the reduced survivorship I identified a native wolf spider that preferred to prey on nicotine free and CYP6B46 silenced larvae compared to control larvae. ...