Periodic Reporting for period 3 - RNAflashbacks (The Neuronal Code of Inheritance)
Reporting period: 2022-08-01 to 2024-01-31
Little is known about non-DNA mediated transgenerational inheritance of parental responses. If inheritance of non-genetic materials is prevalent, it could challenge our most basic assumptions regarding the rules and limits of heredity. One of the biggest questions in the field is whether some neuronal processes can transmit across generations. Until very recently, the possibility that any type of environmental response could become heritable, let alone neuronal responses, was considered blasphemous. In C. elegans nematodes, powerful model organisms which enable robust analysis of heritable responses, small RNAs which regulate gene activity transmit information between generations, owing to a dedicated inheritance machinery. In this project we examine how the worms’ brain produces transgenerational responses. We ask which neuronal RNA molecules act transgenerationally, how do they mediate non-cell autonomous gene regulation, and which neuronal responses can be communicated to the progeny. We will answer these questions, and moreover study the implications that this completely new form of hereditary has for the offspring’s survival. The knowledge that will be gained, and the tools that we engineer to diagnose, erase, maintain, and modulate neuronal heritable effects, could be important for basic research and hopefully also translational in the future.
Towards these goals, I have established a strong and united team of multidisciplinary researchers from
very diverse backgrounds (biology, physics, computer science). We already progressed towards our goal, and showed that small RNA production in the worm’s nervous system triggers effects in the progeny that continue for multiple generations. We identify genes which are regulated transgenerationally by the ancestors’ brain, and describ a number of behavioral phenotypes affected by the environmental conditions that the previous generations experienced. We found natural and also engineered methods for “re-setting” heritable small RNAs responses including neuronally generated responses.
very diverse backgrounds (biology, physics, computer science). We already progressed towards our goal, and showed that small RNA production in the worm’s nervous system triggers effects in the progeny that continue for multiple generations. We identify genes which are regulated transgenerationally by the ancestors’ brain, and describ a number of behavioral phenotypes affected by the environmental conditions that the previous generations experienced. We found natural and also engineered methods for “re-setting” heritable small RNAs responses including neuronally generated responses.
We already advanced beyond the state of the art in the field and obtained novel results that were published and newer results that will be published soon. We discovered, for example, that transient epigenetic responses can nevertheless affect the behavior of the next generations for multiple generations. In addition, by performing lab evolution experiments, we showed that heritable epigenetic responses can change the pace of the worms’ evolution and the composition of their genomes.