Ljubljana, Slovenia 2006/Background

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<center><h3>NASLOV PROJEKTA</h3>
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<center><h3>Engineered Human Cells: SAY NO TO SEPSIS</h3>
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<tr><th>[[Background and Signalling Pathway]]</th></tr>
<tr><th>[[Background and Signalling Pathway]]</th></tr>
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<tr><th>[[Proposal & Approach]]</th></tr>
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<tr><th>[[Project]]</th></tr>
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<tr><th>[[Methods]]</th></tr>
<tr><th>[[Results & Conclusions]]</th></tr>
<tr><th>[[Results & Conclusions]]</th></tr>
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<tr><th>[[Troubleshooting, References & Sponsors]]</th></tr>
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<tr><th>[[Terms & References]]</th></tr>
<tr><th>[[Team members]]</th></tr>
<tr><th>[[Team members]]</th></tr>
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Although in the past years all participating iGEM teams focused on bacteria and yeasts, we decided to modify signalling pathways in higher eukaryotes, t.i. in human cells. This is far more complicated system to understand but we feel that the recently accumulated knowledge enables rational planning of cells with novel properties.
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|border="5" solid #affaaa" cellspacing="1" cellpadding="1" style="border:1px solid #affaaa; background:#fffaf0" | <font style="font size="3" font face="Times New Roman""> <b>Mammalian systems can be a subject of cellular engineering similarly to bacterial cells. We decided to tinker with the existing cell signalling 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 signalling cascade at the »weak spot« - [[Terms & References#Terms|MyD88]], a consensus adaptor 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.</b>
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'''We would like to express our thanks to the Sponsors'''
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komentarji:  
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| [http://www.ki.si/ http://parts2.mit.edu/wiki/images/9/90/Logo_ki2.jpg]
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#na kratko omenimo, kaj smo počeli
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| [http://www.fkkt.uni-lj.si/en/ http://www.fkkt.uni-lj.si/img/menuleft_logo_unilj.gif]
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#fotka HEK293;
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| [http://www.lek.si/ http://parts2.mit.edu/wiki/images/0/09/Lek2.jpg]
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#glede našega dela se uporablja past tense (ker je že naše delo kao končano)
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| [[Image:EU-flag.gif |thumb|120px|EU Synbiocomm]]
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#predlogi glede rubrike home??????
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|}
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#mogoče bi blo lepš, če bi bla prva stran simetrična, torej znakc zgorej, spodej slika, potem črte in potem naprej (Jelka) (Probal sem, kot si predlagala, vendar ne zgleda najbolje. Potem je boljše, da fotke sploh ni. Pač odločit se je treba. Rok)
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#spodnja zelena črta bo še popravljena tako, da bo komplementarna zgornji (Rok)
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#naš logo naj bo na sredini (ne levo)
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'''and Donators'''
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#se sliko mogoče da obkrožt z zeleno. Sej ne vem koko bi se to vidl ... sam tok da vidmi, če ok zgleda, ker mi stran deluje prazno
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Ad Futura, Krka pharmaceutical company, Mediline, Farmadent

Revision as of 14:01, 28 October 2006

Logo-si1.gif Fotka1b.jpg Logo-si1.gif


Engineered Human Cells: SAY NO TO SEPSIS

Line-si4.jpg

Background and Signalling Pathway
Project
Methods
Results & Conclusions
Terms & References
Team members

Line-si3.jpg

Mammalian systems can be a subject of cellular engineering similarly to bacterial cells. We decided to tinker with the existing cell signalling 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 signalling cascade at the »weak spot« - MyD88, a consensus adaptor 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.
File:Model5.jpg.gif
450px

We would like to express our thanks to the Sponsors

http://parts2.mit.edu/wiki/images/9/90/Logo_ki2.jpg http://www.fkkt.uni-lj.si/img/menuleft_logo_unilj.gif http://parts2.mit.edu/wiki/images/0/09/Lek2.jpg
EU Synbiocomm


and Donators Ad Futura, Krka pharmaceutical company, Mediline, Farmadent

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