Hajdú Gábor1, Taisz István1,2
1 Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Budapest, Hungary
2 MRC Laboratory of Molecular Biology, Neurobiology Department, Cambridge, UK
Introduction: In response to tissue damaging noxae, conserved cellular stress responses, xenobiotic detoxification and aversive behaviour facilitate organismal survival. The nematode Caenorhabditis elegans exhibits a concentration dependent biphasic behavioural response to the food ingredient volatile benzaldehyde (BA). Concentrated BA evokes an initial attraction followed by a strong aversion. However, whether aversion is a consequence of acute chemosensation or delayed direct tissue damage is unknown.
Aims: In this study we investigate BA-dependent toxicity, the protective cellular responses and their relationship to the aversive behavior.
Methods: We performed hanging-drop odor exposition experiments for investigating BA-caused organismal effects on acute survival and thermotolerance, and fluorescence microscopy measurements for analyzing adaptive cellular responses of animals. At the behavioural level, lawn-avoidance and chemotaxis assays were carried out.
Results: We demonstrated that BA-treatment induces dose dependent paralysis, death, and reduces thermotolerance. At cellular level, exposure to BA specifically triggered nuclear translocation of the stress-responsive DAF-16/FOXO transcription factor and elevated the expression of the phase-I detoxification enzyme cyp-35b::GFP reporter construction. Further, BA robustly increased autofluorescence of the intestinal aging marker Lysosome Related Organelles (LRO). Interestingly, experiments using LRO biogenesis mutants revealed that LRO-granules are required for survival and thermotolerance upon BA exposure. Currently, employing mutants we test how the abovementioned protective cellular responses regulate the BA-induced avoidance and adaptation.
Conclusion: Our work beyond providing the first evidence on the protective role of C. elegans LRO-s may shed light on the molecular mechanisms involved in benzaldehyde induced toxicity and adaptive aversiveness.
Doctoral School of Molecular Medicine
Supervisor: Dr. Csaba Sőti