Humanized Mouse Model for Pathogen Hemoglobin Binding
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Solution Overview
Problem
Current methods for studying and treating microbial infections do not effectively account for the preferential binding of human hemoglobin by certain microbes, which affects iron acquisition and infection susceptibility, particularly in vertebrates like humans.
Innovation Solution
A method involving the use of an animal model expressing human hemoglobin to study and screen for susceptibility to infections by measuring the binding affinity between hemoglobin and microbes, facilitating the identification of susceptible subjects and potential treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional animal models are used to study microbial infections, then generalizability to human infections is improved, but accuracy in modeling human-specific pathogen interactions deteriorates
Solution Approach 1:
The patent applies local quality by selectively humanizing specific components (hemoglobin) of the mouse model while maintaining other mouse characteristics. This creates a hybrid model with localized human properties where only the hemoglobin portion is humanized, allowing accurate modeling of human-specific pathogen interactions without requiring complete humanization of the animal model.
Solution Approach 2:
The patent implements the nested doll principle by embedding human hemoglobin within the mouse biological system. The human hemoglobin is expressed in transgenic mice, creating a nested structure where human protein functionality is contained within a mouse organism, allowing human-specific pathogen interactions to be studied in a living animal model.
2Measurement precision
If hemoglobin binding affinity is measured to assess microbial virulence, then diagnostic accuracy is improved, but complexity of testing procedures increases
Solution Approach 1:
The patent applies self-service by utilizing the natural binding interaction between pathogens and human hemoglobin as the diagnostic mechanism. The system leverages the pathogen's own hemoglobin-binding properties to assess virulence, requiring minimal external intervention or complex instrumentation beyond measuring binding affinity.
Solution Approach 2:
The patent uses human hemoglobin as an intermediary substance to mediate between the pathogen and the diagnostic measurement system. By measuring how pathogens bind to this intermediary hemoglobin protein, the system translates complex virulence characteristics into quantifiable binding affinity data.
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
This approach allows for the assessment of microbial virulence and susceptibility based on hemoglobin binding affinity, enabling targeted prophylactic treatments and improved understanding of host-pathogen interactions.
Implementation Method 1
S. aureus IsdB preferentially binds hemoglobin derived from humans, and does so with a stronger affinity than mouse hemoglobin
Data Source
AI summary
A method of measuring binding between hemoglobin and a microbe of interest includes: providing hemoglobin from a source of interest; contacting the hemoglobin with a microbe of interest; and measuring the binding affinity between the hemoglobin and the microbe, wherein the binding affinity is indicative of microbe virulence in the presence of the hemoglobin.