INvestigating Heritable Epigenetic Regulation In Tardigrades

Objective

Tardigrades are microscopic invertebrate animals renowned for surviving extreme stresses such as desiccation, cooling to milli-kelvin temperatures, and even cosmic radiation. They owe their resilience partly to cryptobiosis, a reversible state of extreme dormancy. Two major gaps in our knowledge of tardigrades include: whether repeated stress exposure improves tolerance across generations, and whether epigenetic mechanisms underlie such effects. Our preliminary transcriptomic data from heat-stressed Ramazzottius varieornatus revealed differential expression of histone-modifying enzymes, suggesting chromatin-level regulation in stress responses. The INHERIT (INvestigating Heritable Epigenetic Regulation In Tardigrades) project tests the hypothesis that transgenerational stress memory exists in tardigrades and is mediated by epigenetic mechanisms, particularly histone post-translational modifications (HPTMs) influencing chromatin accessibility and gene expression. Using Hypsibius exemplaris as a model, we will: (i) assess whether repeated or parental heat stress enhances survival and recovery within and across generations (WP1); (ii) perform genome-wide profiling of HPTMs (ChIP-seq) and chromatin accessibility (ATAC-seq) alongside transcriptomics (RNA-seq) to identify molecular components (WP2); and (iii) functionally validate candidate histone modifiers via chemical inhibition and RNAi (WP3). We expect to demonstrate transgenerational stress memory in tardigrades, generate the first chromatin landscape mapping for this phylum, and identify key histone modifiers mediating acute and inherited acclimation. By combining cutting-edge epigenomics with experimental physiology, this project is a pioneering research in transgenerational studies in tardigrades, offering insights with implications for biology, biotechnology, and stress-resilient systems.