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Switchable rhodOpsins in Life Sciences

Project description

Understanding structure–function relationships of bistable rhodopsins

Bistable rhodopsins are naturally photosensitive G-protein coupled receptors (GPCRs) responsible for photosensitivity and vision in animals. Bistable rhodopsins are also a potential source of strong optogenetic tools allowing bidirectional control of influential intracellular signalling cascades in all light-using body systems. However, knowledge of their biology and their engineering for optogenetic scopes is restricted due to limited understanding of their structure–function relationships. The EU-funded SOL project will investigate how structural characteristics of these influential photoreceptors determine their bistability, bichromicity, kinetics and G-protein selectivity. The project will apply this knowledge for rational engineering towards colour tuning and G-protein selectivity for optogenetic tools and investigate physiological functions. SOL will produce pioneering optogenetic techniques allowing for definition of GPCR signalling activities.

Objective

Bistable rhodopsins are naturally photosensitive G-protein coupled receptors (GPCRs) that can be toggled between stable ON and OFF states using light. They are responsible for photosensitivity and vision across animals (including humans), and a potential source of powerful optogenetic tools enabling bidirectional control of influential intracellular signalling cascades across all body systems using light. Lack of understanding of structure-function relationships for these proteins curtails understanding of their biology and their engineering for optogenetic purposes.
PI Kleinlogel first demonstrated that chimeras between bistable rhodopsin and ligand GPRCs can be functionally active and provoke a strong physiological response when expressed in vivo. PI Schertler has extensive experience in the structural analysis of rhodopsins and has successfully solved the first structure of a recombinantly expressed bistable rhodopsin. PI Hegemann has longstanding experience in the spectroscopic characterisation and engineering of photoreceptor proteins and is one of the founding fathers of optogenetics. PI Lucas pioneered cellular systems suitable for analysing spectral properties and G protein selectivity and had a leading role in elucidating the physiological role of the bistable rhodopsin melanopsin.
Together, the team aims to understand how structural features of these influential photoreceptors define their bistability, bichromicity, kinetics, and G-protein selectivity (Objective 1). We will exploit this knowledge for rational engineering towards colour tuning and G protein selectivity for optogenetic tools (Objective 2) and to probe physiological functions (Objective 3). The result will be a decisive step towards a general theory of structure-function relationship in photoreceptors and will produce a new generation of powerful optogenetic tools enabling defined GPCR signalling activities in any cell type.

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ERC-SyG - Synergy grant

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(opens in new window) ERC-2020-SyG

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Host institution

PAUL SCHERRER INSTITUT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 552 015,00
Address
FORSCHUNGSTRASSE 111
5232 VILLIGEN PSI
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Aargau
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 552 015,00

Beneficiaries (4)

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