Webinar On Demand

Advancing precision medicine for bipolar disorder: Unveiling the impact of missense mutations via SPR-enabled protein/peptide interaction studies

In the pursuit of precision medicine for bipolar disorder (BD), identifying and functionally characterizing genetic mutations is crucial for refining therapeutic approaches. Dr. Siderovski’s lab recently published a study that exemplified such translational advances by evaluating the impact of a high-penetrance, familial BD-associated missense mutation, R59Q, within the PDZ domain of Regulator of G-protein Signaling 12 (RGS12). Utilizing the Nicoya Alto™ Digital Surface Plasmon Resonance™ (SPR) platform, this research rapidly assessed the mutation’s impact on RGS12 binding affinity to candidate peptide targets—CXCR2, MEK2, and SAPAP3. Results reveal a significant reduction in binding affinity across all tested peptides, suggesting altered protein-peptide interactions attributed to the R59Q mutation. This binding deficiency, corroborated by AlphaFold-derived structural models and molecular dynamics simulations, demonstrates how SPR-based functional testing can accelerate our understanding of disease-related mutations.
 
This approach bridges genetic discovery with functional validation, supporting the translational vision where mutation-specific insights drive personalized pharmacotherapy in psychiatric disorders. By integrating Nicoya’s SPR technology, we move closer to realizing precision treatments informed by unique genetic landscapes—a foundational goal for enhancing disease management and therapeutic outcomes in BD and other complex diseases.
 
Topics covered:
  • What is Digital SPR and how it can be used for binding affinity assessment
  • Insights into how the R59Q mutation impacts protein-peptide interactions
  • The potential of mutation-specific functional testing to drive personalized pharmacotherapy variant differences using mass spectrometry analysis.

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Meet our speakers
Michael Piazza, PhD Director of Applications Development, Nicoya
David Siderovski, PhD Professor, Pharmacology & Neuroscience, UNTHSC