IGEM:Stanford/2009/Notebook/Project Homeostatsis

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The 2009 Stanford iGEM project centers on creating a device that will detect and respond to imbalances in specific subpopulations of T-cells, a type of immune cell. The two populations of T-cells that we are particularly interested in are Th17 cells, a branch of helper T-cells that promote inflammatory responses, and T-regulatory cells, the immunosuppressive response generator. Imbalances in the ratio of this cellular pair have been implicated in a wide rage of immune disorders including rheumatoid arthritis and irritable bowel diseases (IBDs).

Our goal is to sense and correct such imbalances in individuals suffering from IBDs by creating an Escherichia coli-based bacterial device that polarizes immune cells to have directed differentiation along either the Th17 or T-regulatory lineage. Our device will consist of two parts. The first part, our anti-inflammatory device, will control dangerous localized inflammation in the gut by detecting a byproduct of Th17 cell proliferation, nitric oxide, and excreting retinoic acid, a marker that down regulates Th17 populations. Likewise, the second, anti-immunosuppressive device, regulates T-regulatory populations by detecting an analog of tryptophan, a target substrate of T-regulatory markers, and emits interleukin-6, a cytokine that down regulates T-regulatory cells.

We envision our proposed machine as a novel and directed probiotic therapy that will act at the interface between commensal bacteria and human lymphocytes while integrating cutting-edge immunology with synthetic biology.


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