Ljubljana (Slovenia) team presentation at iGEM 2006
17:51
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2 years ago
The Ljubljana, Slovenia team was the Grand Prize winner of iGEM 2006! From their team wiki:
Sepsis claims each year more than 150,000 casualties within the USA and a similar number within the EU. In the absence of an effective treatment of sepsis, the analysis of the signaling pathway may indicate the potential therapeutic targets.
Mammalian systems can be a subject of cellular engineering similarly to bacterial cells. We decided to tinker with the existing cell signaling network of the response to the bacterial infection. Binding of bacterial components (PAMPs – Pathogen associated molecular patterns) to a family of Toll-like receptors activates the cells of the immune system but the exaggerated response may lead to systemic inflammation and sepsis which is often fatal. We designed a feedback loop, which inhibits the signaling cascade at the »weak spot« - MyD88, a consensus adapter protein of the Toll-like receptors. A mathematical model of cell activation with engineered feedback loop was constructed, which predicts the decrease of the cellular activation after the repeated stimulation. Twenty-six new BrioBricks were constructed specially for the mammalian system. We have experimentally confirmed the function of the feedback device by detecting the inhibition of cellular activation after the repeated stimulation. Cell activation decreased without completely deleting the responsiveness to the bacterial infection, thus our engineered cell system represents a type of artificial immunotolerance.The Ljubljana, Slovenia team was the Grand Prize winner of iGEM 2006! From their team wiki:
Sepsis claims each year more than 150,000 ca...all »The Ljubljana, Slovenia team was the Grand Prize winner of iGEM 2006! From their team wiki:
Sepsis claims each year more than 150,000 casualties within the USA and a similar number within the EU. In the absence of an effective treatment of sepsis, the analysis of the signaling pathway may indicate the potential therapeutic targets.
Mammalian systems can be a subject of cellular engineering similarly to bacterial cells. We decided to tinker with the existing cell signaling network of the response to the bacterial infection. Binding of bacterial components (PAMPs – Pathogen associated molecular patterns) to a family of Toll-like receptors activates the cells of the immune system but the exaggerated response may lead to systemic inflammation and sepsis which is often fatal. We designed a feedback loop, which inhibits the signaling cascade at the »weak spot« - MyD88, a consensus adapter protein of the Toll-like receptors. A mathematical model of cell activation with engineered feedback loop was constructed, which predicts the decrease of the cellular activation after the repeated stimulation. Twenty-six new BrioBricks were constructed specially for the mammalian system. We have experimentally confirmed the function of the feedback device by detecting the inhibition of cellular activation after the repeated stimulation. Cell activation decreased without completely deleting the responsiveness to the bacterial infection, thus our engineered cell system represents a type of artificial immunotolerance.«
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