Team:KULeuven/Project

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__NOTOC__
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== Dr. Coli,  the bacterial drug delivery system ==
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!style="text-align:center; background-color:#003E81; border-width:0px; padding:3px;"|[[Team:KULeuven/Project|<font color="#ffffff">The Project</font>]]
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Our team’s project is Dr. Coli, an ''E. coli'' bacterium that produces a drug when and where it is needed in the human body. It does this in an intelligent way, such that the drug production meets the individual patient’s needs. And when the patient is cured, Dr. Coli eliminates itself from the body. To achieve this, a molecular timer registers the time since the last disease signal sensed. Then after a certain time, Dr. Coli self-destructs. However, when the disease flares up again – above a certain noise level - the timer is reset and new drug is produced. Finally, the timer will not start counting during the production of Dr. Coli, thanks to its disease-memory.
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[[Image:kulbanner.jpg|960px]]
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Dr. Coli thus has several advantages over classical drugs, and, if proven successful, could have many medical applications. One example could be the delivery of a vasoactive intestinal peptide as a potential treatment for Crohn's disease.
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=Project brainstorm=
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== Favourite previous iGEM projects ==
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Within the time frame of the iGEM competition, we aim at delivering a proof of concept of Dr. Coli. For the input and output of the system, i.e. sensing the disease signal and producing the appropriate amount of drug, we use a dummy system. The most important assets of our proof of concept are the different control mechanisms. Since these are very much dependent on kinetic and other constants, Dr. Coli heavily relies on proper [https://2008.igem.org/Team:KULeuven/Model/Overview modeling].
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<br>
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==Essential aspects of Dr. Coli==
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'''Maarten Breckpot'''
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===Dr. Coli delivers drugs ''in situ''===
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<div class="floatleft">[[Image:pictogram_input.png|40px]]
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[[Image:pictogram_output.png|40px]]</div>
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Dr. Coli produces a drug when it senses a certain disease signal in the human body. In our project, we replaced the input disease marker by a dummy [https://2008.igem.org/Team:KULeuven/Project/Input input] of anhydrotetracyclin. The proportional [https://2008.igem.org/Team:KULeuven/Project/Output output] drug production is mimicked with a fluorescent protein.
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'''Nathalie Busschaert'''
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===Dr. Coli self-destructs===
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<div class="floatleft">[[Image:pictogram_filter.png|40px]]
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[[Image:pictogram_inverter.png|40px]]</div>
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<div class="floatleft">[[Image:logo_reset.jpg|40px]]
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[[Image:pictogram_celldeath.png|40px]]</div>
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When the patient is cured, Dr. Coli is no longer needed and will eliminate itself from its host. Therefore, we placed an [https://2008.igem.org/Team:KULeuven/Project/Inverter inverter], a [https://2008.igem.org/Team:KULeuven/Project/Inverter molecular timer] and a [https://2008.igem.org/Team:KULeuven/Project/CellDeath cell death] mechanism in cascade. When no input signal is present, the inverter initiates the molecular timer, eventually leading to cell death. Upon renewed presence of the disease signal, the molecular timer is [https://2008.igem.org/Team:KULeuven/Project/Reset reset]. A [https://2008.igem.org/Team:KULeuven/Project/Filter filter], finally, ensures that the timer is not reset when only “noisy” disease signals  are sensed.
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'''Jonas Demeulemeester'''
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===Dr. Coli in production===
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* [http://parts.mit.edu/igem07/index.php/Ljubljana Virotrap Ljubljana 2007]
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[[Image:pictogram_memory.png|40px|left]]
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* [http://parts.mit.edu/igem07/index.php/Princeton RNAi enhanced logic circuit Princeton 2007]
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* Other nice parts/devices:
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** Caltech: Riboswitch design for targeted cell death/molecular sensor
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** Cambridge: Inducible bigger pore protein for E.coli
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** Harvard: Quorum-sensing & targeting!
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** Melbourne: Red/blue light responsive system through chimeric photoreceptors-kinases
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** Peking U: λ-based bistable switch = very powerful
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** UCSF: compartmentalization! Rewired MAPK cascade signaling through scaffolds ≅ circuit board   
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<br> 
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'''Andim Doldurucu'''
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To enable the production of Dr. Coli without it self-destructing, we included a [https://2008.igem.org/Team:KULeuven/Project/Memory memory] device. This is a stable switch that is activated by the first input signal. Only from then on, the clock can start ticking towards cell death.
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'''Jan Mertens'''
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'''Benjamien Moeyaert'''
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* [http://openwetware.org/wiki/IGEM:Harvard/2006/DNA_nanostructures Harvard 20006: nanostructured DNA containers]
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* [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood]
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'''Stefanie Roberfroid'''
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'''Hanne Tytgat'''
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'''Elke Van Assche'''
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* [http://parts.mit.edu/wiki/index.php/MIT_2006 Eau d'E.coli MIT 2006]
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* [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood Berkeley UC 2007]
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* [http://parts.mit.edu/igem07/index.php/Princeton RNAi enhanced logic circuit Princeton 2007]
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'''Nick Van Damme'''
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'''Antoine Vandermeersch'''
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*[http://parts2.mit.edu/wiki/index.php/University_of_Texas_2006 Texas 2006: Edge Detector]
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*[http://parts.mit.edu/igem07/index.php/Rice/Project_B:_Quorumtaxis Rice 2007: Quorumtaxis]
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*[http://parts.mit.edu/igem07/index.php/Berkeley_LBL Berkeley LBL 2007: Solar Bacter]
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'''Dries Vercruysse'''
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'''Sigrid De Keersmaecker'''
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* [http://parts.mit.edu/igem07/index.php/MIT Sensing & removing Hg ions - MIT 2007]
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* [http://parts.mit.edu/igem07/index.php/Edinburgh Self-flavouring yoghurt - Edinburgh 2007]
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* [http://parts.mit.edu/igem07/index.php/Missouri_Miners Biological Timer - Missouri Miners 2007]
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* [http://parts.mit.edu/igem07/index.php/Ljubljana Virotrap - Ljubljana 2007]
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* [http://parts.mit.edu/igem07/index.php/Taipei/Taipei GlucOperon - Taipei 2007]
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* [http://parts.mit.edu/igem07/index.php/Berkeley_LBL Solar Bacter - Berkeley_LBL 2007]
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* [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood - Berkeley_UC 2007]
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== Other ==
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[http://openwetware.org/wiki/IGEM:Idea_exchange Idea exchange - iGEM ideas posted by other teams]
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=Our project=
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Our abstract
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= Our project details=
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== Part 2 ==
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== The Experiments ==
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== Part 3 ==
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= Results =
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Latest revision as of 21:33, 3 October 2008

  dock/undock dropdown  

Dr. Coli, the bacterial drug delivery system

Our team’s project is Dr. Coli, an E. coli bacterium that produces a drug when and where it is needed in the human body. It does this in an intelligent way, such that the drug production meets the individual patient’s needs. And when the patient is cured, Dr. Coli eliminates itself from the body. To achieve this, a molecular timer registers the time since the last disease signal sensed. Then after a certain time, Dr. Coli self-destructs. However, when the disease flares up again – above a certain noise level - the timer is reset and new drug is produced. Finally, the timer will not start counting during the production of Dr. Coli, thanks to its disease-memory.

Dr. Coli thus has several advantages over classical drugs, and, if proven successful, could have many medical applications. One example could be the delivery of a vasoactive intestinal peptide as a potential treatment for Crohn's disease.

Within the time frame of the iGEM competition, we aim at delivering a proof of concept of Dr. Coli. For the input and output of the system, i.e. sensing the disease signal and producing the appropriate amount of drug, we use a dummy system. The most important assets of our proof of concept are the different control mechanisms. Since these are very much dependent on kinetic and other constants, Dr. Coli heavily relies on proper modeling.

Essential aspects of Dr. Coli

Dr. Coli delivers drugs in situ

Pictogram input.png Pictogram output.png

Dr. Coli produces a drug when it senses a certain disease signal in the human body. In our project, we replaced the input disease marker by a dummy input of anhydrotetracyclin. The proportional output drug production is mimicked with a fluorescent protein.

Dr. Coli self-destructs

Pictogram filter.png Pictogram inverter.png
Logo reset.jpg Pictogram celldeath.png

When the patient is cured, Dr. Coli is no longer needed and will eliminate itself from its host. Therefore, we placed an inverter, a molecular timer and a cell death mechanism in cascade. When no input signal is present, the inverter initiates the molecular timer, eventually leading to cell death. Upon renewed presence of the disease signal, the molecular timer is reset. A filter, finally, ensures that the timer is not reset when only “noisy” disease signals are sensed.

Dr. Coli in production

Pictogram memory.png

To enable the production of Dr. Coli without it self-destructing, we included a memory device. This is a stable switch that is activated by the first input signal. Only from then on, the clock can start ticking towards cell death.