Team:NUS Singapore
Probiome
National University of Singapore
Project Abstract
Recent advancements in engineered probiotics have enabled a host of novel whole-cell-mediated medical therapeutics and diagnostics. One such example is scientists using engineered microbes to successfully target tumours in the gastrointestinal tract with minimal collateral damage and invasion. Critical to the function of many such applications are control systems that allow for spatial and temporal activation of the engineered microbe at specific target sites. However, since many existing control systems rely on single input triggers such as temperature or auxotrophy, their reliability is often limited because of evolutionary mutations and environmental perturbations.
Team NUSgem proposes a novel active biocontainment system for the human gut with enhanced specificity and safeguard. Our cascaded toxin-antitoxin killswitch is configured to achieve an OR gate logic upon detection of a physical (temperature) and chemical (phosphate) input. Upon detection of a wastewater environment outside of the human body, the system will inhibit the expression of anti-toxin IM2, thereby allowing the toxin E2 to destroy the engineered microbe. Moreover, we use the bidirectional properties of the pTlpA36 promoter to express the verification of engineered microbe death.
