Ljubljana, Slovenia 2006

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[[Ljubljana, Slovenia 2006 | <font face="trebuchet ms" style="color:#ffffff"> '''Home''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Ljubljana, Slovenia 2006/News | <font face="trebuchet ms" style="color:#ffffff"> '''News''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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<center><font style="font size="5" face="Times New Roman"><b>Engineered Human Cells: SAY NO TO SEPSIS</b></font>
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[[Ljubljana, Slovenia 2006/Team Members | <font face="trebuchet ms" style="color:#ffffff"> '''Team Members''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Ljubljana, Slovenia 2006/Project | <font face="trebuchet ms" style="color:#ffffff"> '''Project''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Ljubljana, Slovenia 2006/Progress | <font face="trebuchet ms" style="color:#ffffff"> '''Progress''' </font>]]
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[[Ljubljana, Slovenia 2006/Back Door | <font face="trebuchet ms" style="color:#ffffff"> '''Internal''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Ljubljana, Slovenia 2006/Slovenia | <font face="trebuchet ms" style="color:#ffffff"> '''Slovenia''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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<tr><th>[[Ljubljana, Slovenia 2006/Background and Signalling Pathway|Background and Signalling Pathway]]</th></tr>
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<tr><th>[[Ljubljana, Slovenia 2006/Project & Model|Project & Model]]</th></tr>
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<tr><th>[[Ljubljana, Slovenia 2006/Methods|Methods]]</th></tr>
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<tr><th>[[Ljubljana, Slovenia 2006/Results & Conclusions|Results & Conclusions]]</th></tr>
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<tr><th>[[Ljubljana, Slovenia 2006/Terms & References|Terms & References]]</th></tr>
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<tr><th>[[Ljubljana, Slovenia 2006/Team members|Team members]]</th></tr>
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Our team is composed of 8 students of different undergraduate programs within the [http://www.uni-lj.si/English/description.asp University of Ljubljana], 3 instructors from the National Institute of Chemistry and 2 supervisors. Project research will be conducted at the [http://www.ki.si/eng/ki/Introduction.html National Institute of Chemistry] (in the group of Prof. Roman Jerala) and at the [http://www.fkkt.uni-lj.si/en/ Faculty of Chemistry and Chemical Technology], [http://openwetware.org/wiki/FCCT_Biochemistry_Lab Biochemistry Chair] (under supervision of Asst. Prof. Marko Dolinar).
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|border="5" solid #affaaa" cellspacing="1" cellpadding="1" style="border:1px solid #affaaa; background:#cedff2" | <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« - [[Ljubljana, Slovenia 2006/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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| [http://www.ki.si/ http://parts2.mit.edu/wiki/images/9/90/Logo_ki2.jpg]
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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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| [http://www.lek.si/ http://parts2.mit.edu/wiki/images/0/09/Lek2.jpg]
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| [[Image:EU-flag.gif |thumb|120px|EU Synbiocomm (thank you Sven)]]
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34 students initially applied for the team. Project proposals were due March 10. We received 13 different project ideas. Both supervisors evaluated the proposed projects and had interviews in the week from April 3 to 7. The 'lab' team members were selected on April 12 and two physics students one week later. In May, we were mainly discussing possible projects and soon focused on a cellular signalisation issue. Laboratory work started on June 7. We were first preparing vector constructs and soon thereafter started testing detection systems (including enzyme-linked immune assays, cell sorter analyses and luminiscence measurements). The model (CellDesigner) of the signalling pathway was developed as well. We work hard to get the anticipated response in genetically modified cells. In parallel, we are preparing the final version of the wiki on another Web server, so expect to have the almost complete version here by the deadline.
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'''and Donators'''
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<br>Ad Futura, Krka pharmaceutical company, Mediline, Farmadent
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<small>''In the center of the photograph is the rectorate building of the University of Ljubljana. Right behind, in the white building the first [http://www.fkkt.uni-lj.si/attachments/521/realka.jpg laboratories] of the Chemistry Department were located since 1919.''</small>
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Revision as of 12:34, 29 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 & Model
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.
Model5.gif

We would like to express our thanks to the Sponsors

[http://www.ki.si/ http://parts2.mit.edu/wiki/images/9/90/Logo_ki2.jpg] [http://www.fkkt.uni-lj.si/en/ http://www.fkkt.uni-lj.si/img/menuleft_logo_unilj.gif] [http://www.lek.si/ http://parts2.mit.edu/wiki/images/0/09/Lek2.jpg]
EU Synbiocomm (thank you Sven)


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

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