IGEM:Stanford/2009/Project Homeostasis/Immunosuppression Device

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Research Proposal
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Anti-Immunosuppression
Device Overview
Parts Design
Challenges
Results
Protocols
Modeling
Overview
Notebook
Results
Future Work
Archived Work


Contents

Summary

Image:Device_2_Overview.JPG

The anti-immunosuppressive device consists of two components: a sensor and a responder. The sensor will detect local concentrations of a marker indicative of Treg-driven immunosuppression. When the levels of this input signal reach above a certain baseline threshold, the sensor will induce activity from the responder. The resulting output signal will modify the local cytokine milieu to support differentiation of pro-inflammatory Th17 cells and repress the immunosuppressive Treg lineage.

Parts Designs

Page Covering Our Parts Designs

Comments


Other Considerations

To what extent will 5-methyltryptophan inhibit growth of our machine? 5-methyltryptophan has been identified as an antimetabolite that induces false feedback inhibition of the trp biosynthetic pathway.

Other potential "input" signals: IL-10, TGF-beta, byproducts of HO-1 Other potential "output" signals: IL-17, IL-1-beta, CpG DNA, TLR stimuli


Challenges


Results


Sources

Treg markers/possible input signals

  • Oliveira et al. Regulatory T cell maintenance of dominant tolerance: induction of tissue self-defense? Transpl Immunol. 2006 Dec;17(1):7-10. Epub 2006 Oct 12. Mentions the small molecule markers produced as a result of Treg-induction of IDO and HO-1.

Trp analogues

  • Heatwole et al. Cloning, nucleotide sequence, and characterization of mtr, the structural gene for a tryptophan-specific permease of Escherichia coli K-12. J Bacteriol. 1991 January; 173(1): 108–115.
  • Kuhn et al. Mutant Strains of Escherichia coli K-12 Exhibiting Enhanced Sensitivity to 5-Methyltryptophan. J Bacteriol. 1972 October; 112(1): 93–101.
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