Chitin Binding Proteins Regulate Intestinal Epithelial Cell Proliferation

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Solution Overview

Problem

Current methods fail to effectively understand and manage microbial signals contributing to intestinal epithelium homeostasis and hyperproliferative diseases, such as colorectal cancer and inflammatory bowel disease, which are linked to the intestinal microbiota.

Innovation Solution

Isolation and use of chitin binding proteins (CBPs) from intestinal microbiota, like Aeromonas veronii and Vibrio cholerae, to increase or decrease epithelial cell proliferation, along with methods to identify and treat subjects at risk of hyperproliferation by administering CBPs or inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chitin binding proteins are used to increase epithelial cell proliferation, then intestinal epithelium homeostasis is improved, but hyperproliferative diseases may be exacerbated

Engineering Contradiction:
Improveintestinal epithelium homeostasisVSAvoidhyperproliferative diseases
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses antibodies to specifically bind to chitin binding proteins, thereby blocking their ability to stimulate epithelial cell proliferation. This parameter change approach selectively inhibits the harmful proliferative signal while preserving the structural and functional roles of CBPs in maintaining intestinal homeostasis.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces antibodies as intermediary molecules that mediate between the chitin binding proteins and epithelial cells. These antibodies act as blocking agents that prevent the direct interaction between CBPs and their receptors on epithelial cells, thereby controlling the proliferative response without eliminating CBP functions entirely.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of information

If microbial signals from intestinal microbiota are studied, then understanding of epithelium homeostasis is improved, but complexity of the system increases

Engineering Contradiction:
Improveunderstanding of microbial signalsVSAvoidsystem complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent extracts and isolates specific chitin binding proteins from the complex intestinal microbiota system. By focusing on these specific proteins rather than studying the entire microbial community, the research simplifies the system while retaining the key functional elements responsible for epithelial cell proliferation signals.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the complex microbial signal system into discrete, studyable components - specifically identifying and characterizing individual chitin binding proteins from different bacterial species. This segmentation allows for targeted investigation of specific molecular mechanisms without being overwhelmed by system complexity.

Inventive Principle:
Principle #1Segmentation

3Productivity

If chitin binding proteins are administered to increase epithelial cell proliferation, then tissue regeneration is improved, but risk of hyperproliferation increases

Engineering Contradiction:
Improveepithelial cell proliferationVSAvoidcontrol of cell growth
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent employs antibodies as feedback control mechanisms that monitor and regulate chitin binding protein activity. When CBPs are present or overexpressed, the antibodies provide negative feedback by binding to and neutralizing excessive proliferative signals, thereby maintaining control over epithelial cell growth rates.

Inventive Principle:
Principle #23Feedback

Data Source

PatentUS9044434B2Method of increasing epithelial cell proliferation with chitin binding protein
Publication Date: 2015.06.02 STATE OF OREGON ACTING BY & THROUGH THE STATE BOARD OF HIGHER EDUCATION ON BEHALF OF UNIV OF OREGON
  • US9044434B2 patent drawing
  • US9044434B2 patent drawing
  • US9044434B2 patent drawing

AI summary

Disclosed herein are methods of increasing epithelial cell proliferation (such as intestinal epithelial cell proliferation) by contacting epithelial cells with one or more CBPs. In some examples, the methods include administering the CBP to a subject, such as a subject in need of increased epithelial cell proliferation. Also disclosed herein are methods of identifying a subject having or at risk of developing hyperproliferation of epithelial cells (such as intestinal epithelial cells). Further disclosed are methods of decreasing epithelial cell proliferation by decreasing expression and/or activity of a CBP and methods of identifying inhibitors of epithelial cell proliferation and/or CBP activity.