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Switchable rhodOpsins in Life Sciences

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.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/cell biology/cell signaling

Call for proposal

ERC-2020-SyG
See other projects for this call

Funding Scheme

ERC-SyG - Synergy grant

Host institution

PAUL SCHERRER INSTITUT
Address
Forschungstrasse 111
5232 Villigen Psi
Switzerland
Activity type
Research Organisations
EU contribution
€ 2 552 015

Beneficiaries (4)

PAUL SCHERRER INSTITUT
Switzerland
EU contribution
€ 2 552 015
Address
Forschungstrasse 111
5232 Villigen Psi
Activity type
Research Organisations
HUMBOLDT-UNIVERSITAET ZU BERLIN
Germany
EU contribution
€ 2 437 500
Address
Unter Den Linden 6
10117 Berlin
Activity type
Higher or Secondary Education Establishments
UNIVERSITAET BERN
Switzerland
EU contribution
€ 2 499 125
Address
Hochschulstrasse 6
3012 Bern
Activity type
Higher or Secondary Education Establishments
THE UNIVERSITY OF MANCHESTER
United Kingdom
EU contribution
€ 2 500 000
Address
Oxford Road
M13 9PL Manchester
Activity type
Higher or Secondary Education Establishments