Light-sensitive channel proteins have attracted much attention as functional molecules, as they possess unique conformations and functions depending on their respective irradiation states. Embedding these proteins in heterogeneous cellular frameworks enabled to gain light-control of cellular and in particular neuronal behaviour. However to date, optogenetic solutions that address endogenous, intracellular biomolecules in a universal fashion remain elusive. The project will apply design and selection strategies aiming at nucleic acid molecules that can be controlled by irradiation with light and which we have developed in preliminary studies. This will now be taken significant steps forward by generating modular allosteric ribonucleic acid (RNA) assemblies that respond to light. These assemblies provide a generic solution and represent long-sought methods to complement the optogenetic toolbox. The aim of this project is the generation of allosteric molecules built from at least two RNA domains; one domain that binds to a soluble photoreceptor protein (PRP) in a light-dependent manner and a second RNA domain, whose protein inhibiting function in turn depends on the binding state of the PRP-recognizing part. We will construct light-responsive allosteric RNA assemblies that can be ubiquitously used in cells and in vivo, independent of specific model organisms, for optogenetic control and spatiotemporal analysis of endogenous, intracellular biomolecule function. The project is highly interdisciplinary and will open novel routes for biomolecule analysis in cells and in vivo. It has implications ranging from life sciences to optogenetics, and from combinatorial biochemistry to synthetic biology. As these new tools will be applicable by any scientist to analyse protein function at high spatiotemporal resolution, the project bears an enormous innovative potential.
Fields of science
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Funding SchemeERC-CG - ERC Consolidator Grants
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