The Neuronal Code of Inheritance

Projektbeschreibung

Die Regeln der Vererbung neu überdenken

Mittlerweile ist erwiesen, dass die Vererbung sowohl die Übertragung genetischer Informationen als auch epigenetischer Merkmale von den Eltern auf die Nachkommen umfasst. Neue Erkenntnisse bei bestimmten Fadenwürmern deuten darauf hin, dass auch bestimmte kleine RNA vererbt werden können, was die grundlegenden Konzepte der genetisch bedingten Vererbung in Frage stellt. Das EU-finanzierte Projekt RNAflashbacks untersucht, wie spezifische kleine interferierende RNA, die in Neuronen gebildet werden, adaptives Gedächtnis an Nachkommen weitergeben können. Die Ergebnisse werden grundlegende Erkenntnisse über die Art der Vererbung und über die Art der Reaktionen liefern, die tatsächlich an die Nachkommen weitergegeben werden können. Ferner wird das Forschungsteam Instrumente zur Modulation der Übertragung solcher Moleküle entwickeln.

Ziel

Little is known about non-DNA mediated transgenerational inheritance of parental responses. If inheritance of non-genetic materials is prevalent, it could challenge our conceptions regarding the rules and limits of heredity. We are in particularly intrigued by the possibility that the nervous system can produce heritable changes. Mechanisms for propagation of responses from the soma to the germline are known. Until very recently, the possibility that any type of environmental response could become heritable, let alone somatic responses, was considered blasphemous. In C. elegans nematodes, exogenously-supplied artificial dsRNA transfers from the soma to the germline, triggering transgenerational small RNA-mediated RNA interference. It is unknown whether endogenous small RNAs can transmit specific information about the environment to the progeny. We will investigate if endogenous siRNAs, which are naturally made in somatic tissues, and in particular in neurons, produce transgenerational responses. Specifically, we will test which RNA molecules act transgenerationally, how do they mediate non-cell autonomous gene regulation, and which responses can be communicated to the progeny. What is the code that transforms particular environmental responses to specific arsenals of heritable RNA molecules? We will answer these questions, and moreover study the implications that this completely new form of hereditary has for the offspring’s survival. Can heritable small RNAs retain adaptive memory? Not only will we elucidate natural transmission of the parents’ activity from generation-to-generation, we will moreover devise means to control these mechanisms. We will engineer tools to diagnose, erase, maintain, and modulate the heritable effects, which would be important for basic research and hopefully also translational in the future.