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Endogenous Redox-Photonic Signaling in Mammalian Neurons

Project description

A new form of cell signalling via photoreceptors in the brain

Vision is initiated by light-sensitive proteins in the eye called opsins. Surprisingly, mammals also possess opsins in internal organs, including the brain, where environmental light cannot easily reach. As such, how these proteins are activated has remained a mystery. The working hypothesis of the ERC-funded PhotonSignaling project is that chemical reactions involving reactive oxygen species inside cells are capable of activating these internal opsins. Building on preliminary evidence of this phenomenon in mouse brain neurons, researchers will determine the precise molecular mechanisms involved, characterise the physiological consequences of this signalling pathway in cells, and explore how broadly it operates. Findings could potentially reshape our understanding of redox biology, cell signalling and diseases such as neurodegeneration, and open entirely new avenues for therapeutic intervention.

Objective

Vision is enabled by photoreceptor proteins in the eye called opsins. In addition to visual opsins, mammals also possess three non-visual opsins, which are highly conserved and also expressed in extra-ocular tissues such as the brain. Recent studies in live mice have shown that these non-canonical opsins are both light-responsive and physiologically active. However, the poor penetration of visible light through hair, skin, bone, and tissue, raises intriguing questions about whether environmental light can conceivably activate opsins found in regions as dark as the inner brain of nocturnal mammals.

I hypothesized that these deep-tissue opsins may be activated by an alternative, internal, source. Specifically, reactive oxygen and nitrogen species (ROS/RNS) can react with cellular biomolecules to form excited states capable of light emission. This chemiluminescence phenomenon was studied intensively decades ago, but has since been overlooked. In the past years, I have established a multi-disciplinary research group aimed at tackling this hypothesis and we have obtained substantial evidence that redox-induced reactions are indeed capable of activating the non-visual opsin 3 (OPN3) in mouse hippocampal neurons in a process that we term “redox-photonic signaling”. However, many fundamental questions remain.

In PhotonSignaling, we will 1) Determine the precise mechanisms of redox-photonic signaling, 2) Determine the physiological consequences of this signaling pathway in mouse neurons, and 3) Explore the extension of this pathway to a broader signaling paradigm.

PhotonSignaling introduces a new dimension to redox biology, photosensory proteins, and cellular signaling. Through this lens, our work has the potential to reshape our understanding of fundamental biology, such as the role of neuropeptides and neurotransmitters, of physiological processes such as aging, and of diseases such as neurodegeneration, to ultimately unlock conceptually new therapeutic interventions.

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(opens in new window) ERC-2025-COG

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Host institution

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
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.

€ 1 999 991,00
Address
INGOLSTADTER LANDSTRASSE 1
85764 Neuherberg
Germany

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Region
Bayern Oberbayern München, Landkreis
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.

€ 1 999 991,00

Beneficiaries (1)

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