BCL10 Protein Complex Isolation for Apoptosis Mechanism
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Solution Overview
Problem
The mechanism through which BCL10 induces apoptosis to inhibit cellular transformation remains unclear, hindering the identification of effective diagnostic and therapeutic targets for diseases associated with BCL10, such as malignancies, inflammatory disorders, and autoimmune diseases.
Innovation Solution
A method for isolating a BCL10-containing protein complex comprising BCL10 and associated proteins like ROS1, LSD1, BTK, KU80, CUL4A, IMP3, thioredoxin, hTID1, DAP3, CDK1/CDC2, PRL1/PTP4A1, and NM23, which allows for the modulation of their interactions and expression for diagnostic and therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If BCL10 is studied in isolation, then the mechanism of apoptosis induction remains unclear, but the complexity of the research approach increases due to lack of contextual information about cellular signaling factors
Solution Approach 1:
The patent applies nesting by isolating BCL10 within its native protein complex context rather than studying it in isolation. The complex contains multiple signaling factors (CARD11, MALT1, and other cellular signaling factors) nested together, allowing simultaneous study of BCL10 and its interacting partners. This nested approach preserves the natural hierarchical organization of the signaling pathway while enabling comprehensive mechanistic investigation.
Solution Approach 2:
The patent employs multi-functionality by using a unified protein complex isolation and characterization approach that simultaneously reveals multiple aspects of BCL10 biology: apoptotic mechanism, NF-κB activation pathway, and interactions with various cellular signaling factors. This single comprehensive method replaces multiple separate experimental approaches, reducing overall research complexity while gaining multifaceted insights.
2Reliability
If BCL10 is studied without its associated proteins, then the apoptotic mechanism cannot be determined, but the quantity of components to be analyzed increases when including the entire complex
Solution Approach 1:
The patent applies segmentation by dividing the complex analysis into manageable components while maintaining their contextual relationships. The isolation method separates the BCL10-containing complex from other cellular proteins, then enables individual identification and characterization of each component (BCL10, CARD11, MALT1, and other signaling factors). This segmented approach allows systematic analysis of multiple proteins without being overwhelmed by the complexity of the entire proteome.
Solution Approach 2:
The patent uses affinity purification and immunoprecipitation techniques as intermediary methods to selectively isolate and capture the BCL10 complex and its associated proteins. These intermediary biochemical methods serve as bridges between the complex mixture of cellular proteins and the specific BCL10-containing complex, enabling reliable identification of all components without requiring direct analysis of every cellular protein.
3Adaptability or versatility
If the BCL10 complex is characterized comprehensively, then new diagnostic and therapeutic targets can be identified, but the time and resources required for isolation and identification increase
Solution Approach 1:
The patent applies preliminary action by establishing a standardized protocol for isolating and characterizing the BCL10 complex that can be reused across multiple studies and applications. The method pre-defines the isolation steps, identification strategies, and characterization approaches, so that once the protocol is developed, subsequent studies can rapidly apply it without reinventing the methodology. This preliminary establishment of methods accelerates future research and translational applications.
Solution Approach 2:
The patent employs parameter changes by optimizing various biochemical parameters (buffer compositions, pH levels, temperature conditions, affinity tags) to enhance the efficiency and speed of complex isolation. By systematically adjusting and optimizing these parameters, the method achieves comprehensive characterization of the BCL10 complex in reduced time compared to non-optimized approaches, making the process more suitable for translational research and clinical application development.
Data Source
AI summary
A method for isolating a protein complex comprising BCL10 and at least one, preferably all, of ROS1, LSD1, BTK, KU80, KU70, CUL4A, IMP3, thioredoxin, hTID1, DAP3, CDK1/CDC2, PRL1/PTP4A1 or NM23. Methods for using this complex to diagnose or prognose diseases including diabetes, obesity, cancer, neurodegenerative disease or inflammatory diseases associated with activation of NF-κB. Methods for distinguishing lean, obese and diabetic subjects based on expression of BCL10 and its ligands are also disclosed. The invention also pertains to pharmaceutical compositions comprising ligands for BCL10 or other components of this complex or agents such as siRNA or miRNA that regulate the expression of the protein components of this complex.