RNAct overview

Global aim

The RNAct research focuses on proteins containing RNA Recognition Motifs (RRM) to posttranscriptionally regulate gene expression and detect specific RNAs. The ability to manipulate these RRMs has wide application potential in bio-analytics and for the creation of synthetic pathways in cells, for example by enabling their activation via small molecule triggers. The 10 Early Stage Researchers (ESRs) trained through RNAct will acquire proficiency for molecular level work on proteins, with an understanding of both experiment and computation. In combination with complementary transversal and entrepreneurial skills training, this will enable the ESRs to constructively contribute to the European bio-economy in both academic and industry settings.

Scientific aims

The project will focus on the following aims:

• Modify the RNA specificity of single-domain RRMs by modulating their side-chain interactions with ssRNA motifs (3-5 nucleotides), so tuning or steering their RNA recognition while maintaining their other functions.
• Allosterically control single-domain RRM-RNA binding via a small ligand that binds an RRM and either triggers RNA-recognition or modifies RNA specificity.
• Design multi-domain RRM protein switches where allosteric changes in the domain linker change the RNA specificity, or where RNA binding changes the linker conformation.
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Early stage researcher (ESRs)

The early stage researchers that will work on this project will employ a variety of computational and experimental methodologies. They will experience both academic and industry environments, intensively through secondments and less formally through an ESR ‘buddy’ system, where experimentally- and computationally-focused ESRs will be paired up with each other. Each ESR will so participate in the research of a participant with a focus different from the main group with which they are associated, and will participate in either lab or in silico hands-on experiments to increase their understanding of the difficulties and ways of thinking in either computational or experimental approaches.