MBI PhD Qualifying Exam
Time: 12pm
Date: 09 March 2018, Friday
Venue: MBI, level 5 meeting room
Supervisors: Prof Linda J. Kenney
Interaction between Salmonella and tumor aggregates on chip
Salmonella enterica serotype Typhimurium, a pathogen causing intestinal infection, is able to target tumors and suppress tumor growth. However, conflicting opinions exist regarding several basic questions in the process, including whether or not motility and chemotaxis are required, where is Salmonella located and what factors determine the tumor-suppressing effect of Salmonella. The mechanisms of Salmonella tumor-targeting and tumor suppression remain undetermined, hindering the therapeutic application of Salmonella. In this research, we employ a 3D cell culture chip to monitor the interaction of Salmonella and tumor aggregates, where we have observed a preferential accumulation of Salmonella along the boundary of the tumor aggregates and a direct killing of tumor cells by Salmonella. We hypothesize that Salmonella tumor-targeting is driven by bacterial chemotaxis and that tumor production of lactic acid works as a chemoattractant. We will test the hypothesis by experiments with chemotactic mutants, a capillary assay and a competition assay of aggregates with variable levels of lactic acid secretion. We will further determine the location of Salmonella in tumor aggregates and characterize the cell death induced by Salmonella. Juxtaposed with cell death of epithelial cells and macrophages described in previous study, we will speculate how Salmonella kills cells in the interaction with tumors and determine what factors regulate the tumor-suppressing effect of Salmonella by performing experiments with different mutants of critical virulence factors in Salmonella pathogenesis. This study will optimize the modification of Salmonella as a therapeutic agent and promote the general application of bacterial therapy in treating cancer.
**Please note the examination following the seminar is closed-door**
