Browsing by Author "Dou, Jennifer"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Examination of Stationary-Phase Gene Expression in Context of Real-World Applications of Synthetic Microbes
    (2023-04-21) Dou, Jennifer; Bennett, Matthew
    As synthetic biology attempts to move into real-world applications, it must confront the additional challenges posed by natural environments such as soil, wastewater, and the gut. Working within the gut microbiome, we sought to increase the range and potential utility of therapeutic probiotics by introducing a simple logic-gate system into the guts of mice and showing that it could work there. We were unsuccessful in this, but along the way explored issues such as what an effective reporter of gene expression that can be detected from within the mammalian gut might look like, and the additional challenges of making genetic circuitry work in stationary-phase. We developed inducible stationary-phase promoters which can be turned on by chemical inducers such as IPTG and aTc, and showed that they express primarily in stationary phase and are more effectively induced when cells are in stationary phase, compared to similar exponential-phase promoters.
  • Thumbnail Image
    Item
    Synthetic Biology and the Gut Microbiome
    (Wiley, 2018) Dou, Jennifer; Bennett, Matthew R.
    The gut microbiome plays a crucial role in maintaining human health. Functions performed by gastrointestinal microbes range from regulating metabolism to modulating immune and nervous system development. Scientists have attempted to exploit this importance through the development of engineered probiotics that are capable of producing and delivering small molecule therapeutics within the gut. However, existing synthetic probiotics are simplistic and fail to replicate the complexity and adaptability of native homeostatic mechanisms. In this review, the ways in which the tools and approaches of synthetic biology have been applied to improve the efficacy of therapeutic probiotics, and the ways in which they might be applied in the future is discussed. Simple devices, such as a bistable switches and integrase memory arrays, have been successfully implemented in the mammalian gut, and models for targeted delivery in this environment have also been developed. In the future, it will be necessary to introduce concepts such as logic-gating and biocontainment mechanisms into synthetic probiotics, as well as to expand the collection of relevant biosensors. Ideally, this will bring us closer to a reality in which engineered therapeutic microbes will be able to accurately diagnose and effectively respond to a variety of disease states.