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CSB Seminar Series – Ben Scott and Cristina Gutierrez-Vazquez – Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease

Name: CSB Seminar Series – Ben Scott and Cristina Gutierrez-Vazquez – Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease
Start: 2021-10-15T11:00:00-04:00
End: 2021-10-15T12:00:00-04:00
Location: Virtual

October 15, 2021 @ 11:00 am - 12:00 pm

Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease

Benjamin Scott, PhD: Advisor, Business Development and Partnerships Engagement, Genome Foundry, Concordia University

and

Cristina Gutiérrez Vázquez, PhD: Scientist at Regeneron Pharmaceuticals

Abstract

Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal tract. Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology. Based on the role of eATP in intestinal inflammation, we developed yeast-based engineered probiotics that express a human P2Y2 purinergic receptor with up to a 1,000-fold increase in eATP sensitivity. We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization. These self-tunable yeast probiotics suppressed intestinal inflammation in mouse models of IBD, reducing intestinal fibrosis and dysbiosis with an efficacy similar to or higher than that of standard-of-care therapies usually associated with notable adverse events. By combining directed evolution and synthetic gene circuits, we developed a unique self-modulatory platform for the treatment of IBD and potentially other inflammation-driven pathologies.