Potatoes (Solanum Tuberosum) are a staple of diets across the globe and have developed defensive toxins that protect itself from eukaryotic pathogens. These toxins, notably α-Solanine and α-Chaconine, are known to cause cell death in vitro and acute poisonings in humans. More recently, these toxins have been found to bioaccumulate within physiological systems, yet the effects of chronic exposure remain unknown. α-Solanine can interfere with acetylcholine signaling, membrane dynamics, and mitochondrial and ion channel function, however the molecular targets involved are not well characterised.
To better understand how these toxins interact with human physiology, we performed a whole genome CRISPR KO screen to identify the mechanisms these toxins use to trigger cell death. From this we found multiple new gene targets or modifiers of toxin-induced cell death and were able to map biological pathways the toxin targets. We then confirmed these findings genetically and pharmacologically, allowing us to identify several drug candidates which block α-Solanine toxicity in vitro. Thus, using genome-wide CRISPR screening technologies, we were able to fundamentally identify novel targets of α-Solanine and guide the development of drug candidates.