Taste Papillae Cells for Olfactory Receptor Screening

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Solution Overview

Problem

The lack of a suitable model system for identifying modulators of olfactory receptors in mammalian systems has hindered progress in understanding mammalian olfactory sensation.

Innovation Solution

Methods for identifying modulators, ligands, enhancers, and blockers of olfactory receptors are developed by detecting receptor activity in taste papillae cells or cell membranes, using techniques such as intracellular Ca2+ level determination or reporter agents, with test agents being natural or synthetic chemicals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional olfactory receptor study methods are used, then research on mammalian olfactory sensation can proceed, but progress is hampered by the lack of a suitable model system for identifying modulators

Engineering Contradiction:
Improvemodel system applicabilityVSAvoidresearch feasibility
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent uses taste papillae cells as an intermediary model system to study olfactory receptors. Instead of directly studying olfactory receptors in their native olfactory epithelium (which lacks a suitable model system), the invention transfers olfactory receptor expression to taste papillae cells that can be easily cultured and manipulated. This intermediary system bridges the gap between the need for physiological relevance and the need for experimental accessibility.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If taste papillae cells are used to express olfactory receptors, then a suitable model system for identifying modulators is created, but requires development of new detection methods for receptor activity

Engineering Contradiction:
Improvemodel system capabilityVSAvoiddetection method complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent replaces direct measurement of olfactory receptor activity (which would require complex olfactory tissue preparation) with calcium imaging techniques. By measuring intracellular calcium levels as a proxy for receptor activation, the invention substitutes a complex physiological measurement system with a more tractable biochemical assay that can be performed in cultured cells.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs fluorescent calcium indicators that change color or fluorescence intensity in response to calcium concentration changes. When olfactory receptors are activated in taste papillae cells, the resulting calcium influx is detected through fluorescence microscopy, providing a visual readout of receptor activity that simplifies the detection process.

Inventive Principle:
Principle #32Color changes

3Productivity

If modulator screening is performed using this new model system, then identification of ligands and modulators is enabled, but requires extensive testing with test agents

Engineering Contradiction:
Improvemodulator identification efficiencyVSAvoidscreening time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent creates a universal screening platform using taste papillae cells that can test multiple types of olfactory receptors with a single cell line system. Once the taste papillae cell model is established, it can be used to screen various olfactory receptors, ligands, and modulators in a standardized format, eliminating the need to develop separate assay systems for each receptor and thereby reducing overall screening time.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

These methods provide a model system for identifying and characterizing olfactory receptor ligands and modulators, enabling research, diagnostic, therapeutic, and drug screening applications, and allowing manipulation of olfactory responses.

Implementation Method 1

olfactory receptors constitute the largest subfamily of G protein-coupled receptors with up to a thousand members expected in mammalian species

Methodology Applied
Scientific EffectG protein-coupled receptor signaling:

Data Source

PatentUS10908147B2Methods of identifying modulators of olfactory receptors
Publication Date: 2021.02.02 MONELL CHEMICAL SENSES CENTER
  • US10908147B2 patent drawing
  • US10908147B2 patent drawing
  • US10908147B2 patent drawing

AI summary

Described herein are mammalian taste papillae cells, cell lines, and cell membranes, methods, and kits for identifying agents, including ligands for olfactory receptors and enhancers and blockers thereof, that bind to or modulate the activity of olfactory receptors on mammalian taste papillae cells.