Light-Sensitive GPCR Pathway Control via Wavelength Segmentation

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Solution Overview

Problem

Current methods for controlling G-protein coupled receptor (GPCR) pathways are limited by the need for ligands and slow time courses, making it challenging to simultaneously or separately activate specific pathways in cellular systems, particularly in neuronal circuits and living animals.

Innovation Solution

Development of light-sensitive GPCRs with a light-sensitive extracellular domain and a heterologous intracellular domain that can modulate intracellular signaling pathways, allowing activation by different wavelengths and deactivation by distinct light wavelengths, enabling precise control of GPCR pathways in various cell types, including neurons.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If traditional ligand-based methods are used to control GPCR pathways, then pathway activation can be achieved, but the time course is slow and simultaneous activation of multiple pathways is difficult

Engineering Contradiction:

Improvetime course of pathway activationVSAvoidability to simultaneously activate multiple pathways

Core Design Contradiction:

SpeedVSAdaptability or versatility

Solution Approach 1:

The patent divides the control of GPCR pathways by using different wavelengths of light to activate different opsins, which in turn activate different G-protein pathways. Each opsin-GPCR construct is tuned to respond to a specific wavelength, allowing independent and simultaneous control of multiple pathways through wavelength-specific illumination.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a universal light-controlled system where a single platform (opsin-based GPCR) can control multiple different signaling pathways (Gs, Gi, Gq) by simply changing the wavelength of light. This multi-functional system allows one system to perform multiple pathway activations without requiring separate ligand applications for each pathway.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Ease of operation

If ligand-based activation of GPCRs is used, then pathway modulation is possible, but the method is invasive and lacks precision in temporal control

Engineering Contradiction:

Improveprecision of temporal controlVSAvoidinvasiveness of ligand application

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the chemical mechanism of ligand binding with an optical mechanism using light-activated opsins. Instead of applying chemical ligands that require diffusion, binding, and washout procedures, the system uses photons to directly activate the opsin domains, enabling non-invasive, rapid, and precisely temporally controlled pathway activation without the harmful effects of chemical interventions.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Device complexity

If conventional GPCR activation methods are used, then signaling pathway modulation occurs, but separate activation of specific pathways requires multiple different ligands and procedures

Engineering Contradiction:

Improvenumber of ligands and procedures requiredVSAvoidspecificity of pathway activation

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The patent changes the control parameter from chemical ligand identity to physical light wavelength. By tuning the wavelength of light, different opsins with specific spectral sensitivities can be activated, providing reliable and specific activation of different G-protein pathways (Gs, Gi, Gq) without requiring multiple different chemical ligands and complex application procedures.

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables non-invasive, rapid, and precise modulation of neuronal activity and signaling pathways, facilitating the study of neural circuits and potential therapeutic applications by using light-activated switches like vertebrate rhodopsin and channelrhodopsin, and melanopsin variants for sustained or transient activations.

Implementation Method 1

a light-sensitive extracellular domain capable of being activated by light having a first wavelength

Methodology Applied

Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 2

Upon binding of a ligand to an extracellular portion of a GPCR, a signal is transduced within the cell that results in a change in a biological or physiological property of the cell

Methodology Applied

Scientific EffectSignal transduction:

Data Source

PatentUS10227391B2System and method for controlling G-protein coupled receptor pathways

Publication Date: 2019.03.12 CASE WESTERN RESERVE UNIV

AI summary

A light-sensitive G-protein coupled receptor includes a light sensitive extracellular cone opsin or melanopsin domain and a hetorologous intracellular domain capable of modulating an intracellular signaling pathway.