Deciphering molecular mechanisms underlying transgenerational inheritance of acquired traits

The validity of Jean-Baptiste de Lamarck’s hypothesis of inheritance of acquired traits has long been a matter of great debate. The research plan proposed here, will utilize technically and conceptually innovative approaches to explore the molecular, physiological and mechanistic basis of transgenerational inheritance of acquired traits in C.elegans. First, I will determine transcriptomic changes in the nervous system in the F5 generation of starved ancestors. To detect subtle, but potentially biologically-important adaptations in highly specialized neurons, I will make use of INTACT that allows for tissue-specific mRNA isolation, which will then be subjected to next-generation sequencing and bioinformatical analyses. Second, I plan to identify stress-dependent physiological and behavioral adaptations in locomotory behavior, metabolism and sensory perception. Importantly, to decipher the relative contribution of small RNAs in mediating molecular and physiological behavioral changes, the previously described experiments will not only be performed in descendants from N2, but also from neuron-specific Dicer-1-deficient ancestors. Dicer-1 is critical for the generation of distinct classes of small RNAs, i.e. miRNAs and endo-siRNAs. Finally, upon identification and subsequent GFP-tagging of genes that are transgenerationally deregulated upon ancestral starvation, I will perform unbiased forward genetic screens using EMS. Mutagenesis prior to or after starvation will allow for the identification of novel signals involved in the initiation of the original stress response, as well as for the maintenance and inheritance of adapted gene expression across generations, respectively.