Engineered Yeast Sensor Cells for Visual Pathogen Detection

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Solution Overview

Problem

Current methods for detecting pathogens and contaminants lack simplicity and effectiveness for use outside laboratory settings, particularly in detecting peptide ligands associated with human disease agents, agricultural agents, and bioterrorism agents without the need for instrumentation.

Innovation Solution

Engineered baker's yeast cells equipped with G-protein coupled receptors (GPCRs) that can detect peptide ligands by triggering a visible color change, using lycopene as a reporter gene product, allowing for rapid and non-technical visual detection of agents in samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If traditional pathogen detection methods are used, then detection accuracy can be maintained, but the methods require complex instrumentation and laboratory settings

Engineering Contradiction:

Improvesimplicity of detection methodVSAvoidinstrumentation requirement

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical/instrumental detection systems with a biological sensing system. Engineered yeast cells with GPCRs and reporter genes detect peptide ligands through natural biological processes, producing visual signals without requiring instrumentation. This substitutes mechanical detection apparatus with a self-reporting biological system.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The engineered yeast cells are self-sufficient detection devices that contain all necessary components (GPCRs, signaling pathways, reporter genes) within a single cell. The cells autonomously detect peptide ligands and generate visual signals without external instrumentation or complex processing, making the detection system portable and simple to operate.

Inventive Principle:

Principle #25Self-service

2Adaptability or versatility

If traditional detection methods are used, then reliable pathogen identification can be achieved, but the methods are not suitable for field or home testing

Engineering Contradiction:

Improveapplicability outside laboratoryVSAvoiddetection effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the detection parameters from instrumental measurements to visual observations. The reporter genes produce pigmented compounds or fluorescent proteins that can be detected by the naked eye or simple devices, transforming the detection output from complex instrumental data to simple visual signals suitable for field conditions.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The engineered yeast cells serve multiple functions: they detect specific peptide ligands, amplify the signal through cellular processes, and produce visual outputs. This multi-functionality within a single biological system enables reliable detection across different settings from laboratories to field environments.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Measurement precision

If GPCRs are engineered for higher sensitivity, then detection capability improves, but the engineering process becomes more complex

Engineering Contradiction:

Improvedetection sensitivityVSAvoidGPCR engineering complexity

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The GPCRs are pre-engineered with high sensitivity and specificity for target peptide ligands before deployment. The yeast cells are constructed in advance with optimized GPCR-reporter gene circuits, allowing them to detect low concentrations of analytes without requiring complex engineering during actual detection operations.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The reporter gene systems provide feedback signals that amplify the detection response. When GPCRs bind peptide ligands, they trigger signaling cascades that activate reporter genes, producing visual signals that feedback to indicate detection. This amplification mechanism enhances sensitivity without requiring equally complex engineering.

Inventive Principle:

Principle #23Feedback

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 straightforward, instrument-free detection of various agents, including pathogens and contaminants, by utilizing engineered yeast cells that produce a visible pigment in response to specific peptide ligands, enhancing sensitivity and specificity through directed evolution of GPCRs.

Implementation Method 1

GPCR signaling pathways are highly conserved among diverse species. Furthermore, GPCR-activation of the Mitogen-activated protein kinase (MAPK) phosphorylation cascade is conserved from yeast to mammals

Methodology Applied

Scientific EffectG-protein coupled receptor signaling:

Implementation Method 2

binding of the analyte to the receptor triggers a detection event that is indicative of the presence of the agent. The reporter can be coupled to the receptor

Methodology Applied

Scientific EffectReporter gene expression:

Data Source

PatentUS11899014B2Detection of analytes using live cells

Publication Date: 2024.02.13 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

The present invention provides sensor cells comprising a receptor that binds to an analyte indicative of the presence of an agent, where binding of the analyte to the receptor triggers a detection event that is indicative of the presence of the agent. In certain embodiments, the detection event is appearance of a reporter detectable by the naked eye. The present invention also provides uses of such sensor cells for detecting the presence of an agent in a sample.