Chroco: Chronology of coping with a toxic stress: from omic to apical responses – Chroco

The Chroco project proposes to investigate simultaneously both dimensions of the toxicant exposure, concentration and time, to characterize contamination impacts from omics to apical levels with deepened findings contextualized by exposure intensity and duration. In particular, the project will address the following questions: would time and dose-dependent changes in the transcriptome (representing omics) i) be related (in terms of mode(s) of action) to effects observed on the energy budget of organisms (representing apical effects)? ii) be considered as early warnings of damages related to apical endpoints and their consequences on population dynamics (earlier in time or at lower exposure concentration)? iii) demonstrate coping capacities of organisms?

The Chroco project relies on two main hypotheses. (1) Gene expression is dynamic and a targeted time will influence the output of any transcriptomic or proteomic study, since inactive genes/pathways will be missed. In addition, punctual observations cannot allow determining the kind of effect involved in the perturbation. (2) Beyond the molecular events directly elicited by a contaminant exposure, an orchestrated molecular response will also be induced to cope with the disturbances. Those regulatory processes, involved in organism homeostasis maintenance in a changing environment (food resources, temperature…) will notably rely on the cell signalling pathways allowing to regulate the energy trade-off between the main metabolic functions like growth, reproduction, immunity or global stress response. Consequently, the global transcriptional response observed at a given time both reflects the direct impact of the contaminant and the regulatory processes aiming at maintaining or restoring a global physiological homeostasis.

The Chroco project proposes to work, as a case study, on Daphnia magna exposed to the endocrine disrupting compound di-n-butyl phthalate (DBP). D. magna is a model species in ecotoxicology, whose genome is sequenced and whose physiology is well-known. DBP is a phthalic acid ester (phthalates), used as a plasticizer for PVC, and one of the most frequently detected and abundant in surface waters.

The first originality of the project is to study at the same time the time- and dose-resolved responses of D. magna to DBP, from the transcriptomic level up to repercussions on life history traits and population dynamics with intermediate targeted measurements to validate the underlying mechanisms. Hence, we will dissect the chronology/”dosology” of a metabolic disrupting compound effects in a model crustacean at an unprecedented depth. Such investigations will require modelling developments, and the second originality of the Chroco project is to address the challenge to develop a statistical workflow to model finely dose- and time-resolved high-throughput omic data.

The expected results include the production of original knowledge, the release of an open source data analysis tool, and insight into the acute-to-chronic gap, which is essential for environmental risk assessment. The project will bring a proof of concept on how to use omics in regulatory context and how to include the time dimension in adverse outcome pathway approaches.