Engineering of designer switches for controlling protein expression in eukaryotic model organisms (A05)

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Within the second funding period we have successfully implemented RNA-based switches of gene expression allowing for induction of gene expression in the model organism C. elegans. The developed switches enabled the implementation of a Huntington´s Disease model that would not have been possible in a constitutive setup due to the cytotoxicity of the aggregation-prone Huntingtin variants. Within the third funding period we will optimize the dynamic range of the switches and add OFF-switches to the repertoire available in C. elegans. Furthermore, we will explore whether additional ligands can be utilized in the nematode. In addition to utilizing ribozymes as expression platforms, we will develop other ways of implementing RNA aptamers in genetic switches such as controlling splice site or poly-A signal accessibility. The developed RNA switches will be applied for controlling gene expression in C. elegans in collaborative efforts with E. Deuerling and M. Gamerdinger (projects A01 and A07), in human cell lines together with M. Groettrup (project C01), and in A. thaliana with E. Isono (project C08).