Graduate Seminar Series: Cell and Tissue Stream
Graduate Seminar Series for the Institute of Biomedical Engineering (BME). This day is for cell and tissue stream presenters.
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Presentation Title: Leveraging probiotic-derived membrane vesicles as a postbiotic therapeutic for Crohn’s disease
Abstract: Bacterial membrane vesicles (BMVs) are bilipid nanoparticles produced as a conserved method of intercellular communication for the delivery of diverse bacterial products. These biological nanoparticles have potential for significant biomedical application, such as in the context of Crohn’s disease (CD). CD is a chronic inflammatory bowel disease that is influenced by host-microbe interactions. In CD, NOD2 signalling pathway is disrupted by genetic and environmental factors. Overcoming NOD2 hypoactivity presents a novel therapeutic target for restoring host-microbe communication in CD. However, muramyl dipeptide (MDP), the NOD2 agonist, is a poor drug candidate due to its large molecular weight and hydrophilicity. MDP is a product of bacterial peptidoglycan (PG) degradation and is a potential cargo of BMVs. We propose the application of probiotic-derived BMVs as an MDP delivery system for the management of CD. In preliminary work, we demonstrated that isolated BMVs from B. subtilis carry PG fragments capable of inducing IL-8 secretion and CXCL1 expression in HCT116 cells in a NOD2-dependent manner. In addition, we applied metabolic engineering approaches to optimize BMV production and MDP packaging through the inducible expression of PG hydrolases in both Gram-positive and Gram-negative bacteria. Overexpression of PG hydrolases resulted in increased production of BMVs and coincided with increased NOD2 activity of bacterial supernatants. Facilitated delivery of MDP by probiotic-derived BMVs demonstrates a promising strategy to enhance NOD2 signalling activity. This work contributes to the advancement of complementary CD therapeutics, towards the goal of improving therapeutic outcomes and quality of life for CD patients.
Supervisor Name: Radhakrishnan Mahadevan
Year of Study: 2
Program of Study: MASc
Zoom link: https://us02web.zoom.us/j/89610372821?pwd=azd4SCtYVWtreVovaGNPV1c2NGY2Zz09
Meeting ID: 896 1037 2821
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