Team:Minnesota/ModelingComparator

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Latest revision as of 22:49, 28 October 2008

Minnesota Home	Team Comparator Home	The Team	The Project	Parts Submitted to the Registry	Modeling	Notebook

Computational Tools (all teams invited to use SynBioSS)

Team Comparator is also developing two tools named the "SynBioSS Designer" and "SynBioSS Wiki". SynBioSS stands for Synthetic Biology Software Suite. It is a software suite that can assist in synthetic biology applications. It is freely available at synbioss.sourceforge.net [1]. As with any engineering problem, modeling the behavior of a putative synthetic biological system is a key step in the design process. To date, many of these simulations of synthetic systems have used coarse-grained models and deterministic kinetic equations. Our team, however, strives to use stochastic models spanning multiple time scales. One major bottleneck is that the detailed molecular-level reaction networks required for such simulations are time consuming to construct. Moreover, while many of the promoters, operators, repressors, etc. used in synthetic biology have been well studied, the necessary quantitative information is scattered throughout the literature. The SynBioSS Designer facilitates the construction of detailed and accurate models, while the SynBioSS Wiki addresses the challenges of data collection and curation.

Computational Tools

A schematic representation of how the Designer translates a series of BioBricks into a kinetic model of the reaction network.

Both Designer and Wiki can be found via the SynBioSS home page.

SynBioSS Designer

SynBioSS Designer is an application for the automatic generation of sets of biomolecular reactions. This software allows a user to input the molecular parts involved in gene expression and regulation (e.g. promoters, transcription factors, ribosomes, etc.) The software then generates complete networks of reactions that represent transcription, translation, regulation, induction and degradation of those parts. To facilitate the creation of detailed kinetic models of synthetic gene networks composed of BioBricks, we have adapted SynBioSS Designer to automatically generate a kinetic model from a construct composed entirely of BioBricks. A NetCDF or SBML file is generated for simulations.

SynBioSS Wiki

SynBioSS Wiki's main page as of October 28th, 2008.

The inaccessibility of requisite kinetic data complicates the generation of detailed mechanistic models. We address this barrier by creating a web accessible database curated by users in a “Wiki” format. SynBioSS Wiki is a significant extension of the open-source Mediawiki software. The Wiki stores reaction kinetic data in a formatted and searchable scheme with references to the relevant literature. This framework allows for the input of reactions whose rates are described either by elementary first & second order rate equations or any arbitrarily complex rate equation defined using MathML (e.g. Hill type reactions). Reactions may be searched via participating molecules which may be proteins, DNA sequences, small molecules, etc. Once located, reactions of interest (along with their associated kinetic data) may be collected. The completed model may be exported in SBML format for additional editing or simulation.

It is also through the SynBioSS Wiki databases that SynBioSS Designer can access and proliferate kinetic information related to the simulation of BioBricks, thus extending the utility of the database for the benefit of the greater modeling community. To jumpstart the process, we have entered the known biomolecular interactions in the expression and regulation of well-studied operons, such as the lactose, the tetracycline and the arabinose operons.

Mathematical Modeling for Team Comparator

We will be modeling our system using our in-house software called Synthetic Biology Software Suite (SynBioSS is open source available http://synbioss.sourceforge.net/) and a network of reactions. Our first try at the reaction network is shown below.

First Reaction Network

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-{|align="justify"
-|The Minnesota iGEM '08 team consists  of groups working on two different projects. One team is located primarily in Minneapolis and is designing a comparator for their project. The other team is based in St. Paul and is working on a time bomb.
-|[[Image:Minnesota.gif|200px|right|frame]]
-|-
-|
-'''Team Comparator'''
-|-
-|Control systems are an integral component of almost all aspects of life. Whether it is in industrial, biological, or chemical applications, controllers provide a way to keep systems functioning properly. A vital part of any control system is the comparator. This component compares a set point value and a measured value, and determines which is larger. It then sends the appropriate signal to the controller, which reacts to bring the system back to the set point. In typical applications, the controller equipment is electronic. However, our team set out to create a comparator using only genetic components. This comparator could potentially be used as part of a new, solely biological control system that could be used to treat many diseases afflicting humans, for example diabetes. This comparator could compare the blood sugar of a patient to what it should be, and send this result to a control system that could compensate, for example by changing the levels of insulin.
-In order to undertake this task, a system involving six genes was designed. For our system, the two inputs (one representing the set point and one representing the measured value) are IPTG and ATC. These inputs will activate the transcription of the LacI and TetR proteins, and set in motion the rest of the system to produce the outputs. Depending on the amounts of the two inducer molecules added to the system, either green fluorescent protein (GFP) or red fluorescent protein(RFP) will be produced. The actual design of the system can be seen below. In order to complete this project, a total of six genes will have to be cloned into plasmids, and two new BioBrick parts will be produced. One will be a TetR and p22-MNT dual-repressed promoter, and the other will be a LacI and lambdaphage cI dual-repressed promoter. We will also build mathematical models and conduct computer simulations that will help with the designs. This project will pave the way for other parts of a true genetic PID controller to be produced, which could be an exciting scientific development in the near future.
-|[[Image:Team_Pic_Minnesota.jpg|300px|right|thumb|Team Comparator]]
-|-
-|
-|
-|}
-<!--- The Mission, Experiments --->
 {| style="color:gold;background-color:#800000;" cellpadding="3" cellspacing="1" border="1" bordercolor="#fff" width="90%" align="center"
 !align="center"|[[Team:Minnesota|<font color="gold">Minnesota Home</font>]]
@@ Line 33: / Line 9: @@
 |}
+'''Computational Tools (all teams invited to use SynBioSS)'''
+Team Comparator is also developing two tools named the "SynBioSS Designer" and "SynBioSS Wiki". SynBioSS stands for '''Syn'''thetic '''Bio'''logy '''S'''oftware '''S'''uite. It is a software suite that can assist in synthetic biology applications. It is freely available at synbioss.sourceforge.net [http://synbioss.sourceforge.net]. As with any engineering problem, modeling the behavior of a putative synthetic biological system is a key step in the design process. To date, many of these simulations of synthetic systems have used coarse-grained models and deterministic kinetic equations. Our team, however, strives to use stochastic models spanning multiple time scales. One major bottleneck is that the detailed molecular-level reaction networks required for such simulations are time consuming to construct. Moreover, while many of the promoters, operators, repressors, etc. used in synthetic biology have been well studied, the necessary quantitative information is scattered throughout the literature. The SynBioSS Designer facilitates the construction of detailed and accurate models, while the SynBioSS Wiki addresses the challenges of data collection and curation.
-===Mathematical Modeling===
+== Computational Tools ==
+[[Image:SynBioSS_Designer.jpg|300px|right|thumb|A schematic representation of how the Designer translates a series of BioBricks into a kinetic model of the reaction network.]]
+Both Designer and Wiki can be found via the SynBioSS [http://synbioss.sourceforge.net home page].
+=== SynBioSS Designer ===
+SynBioSS Designer is an application for the automatic generation of sets of biomolecular reactions. This software allows a user to input the molecular parts involved in gene expression and regulation (e.g. promoters, transcription factors, ribosomes, etc.) The software then generates complete networks of reactions that represent transcription, translation, regulation, induction and degradation of those parts. To facilitate the creation of detailed kinetic models of synthetic gene networks composed of BioBricks, we have adapted SynBioSS Designer to automatically generate a kinetic model from a construct composed entirely of BioBricks. A NetCDF or SBML file is generated for simulations.
+=== SynBioSS Wiki ===
+[[Image:SynBioSS_Wiki.jpg|300px|right|thumb|SynBioSS Wiki's main page as of October 28th, 2008.]]
+The inaccessibility of requisite kinetic data complicates the generation of detailed mechanistic models. We address this barrier by creating a web accessible database curated by users in a “Wiki” format. SynBioSS Wiki is a significant
+extension of the open-source Mediawiki software. The Wiki stores reaction kinetic data in a formatted and searchable
+scheme with references to the relevant literature. This framework allows for the input of reactions whose rates are described either by elementary first & second order rate equations or any arbitrarily complex rate equation defined using MathML (e.g. Hill type reactions). Reactions may be searched via participating molecules which may be proteins, DNA sequences, small molecules, etc. Once located, reactions of interest (along with their associated kinetic data) may be collected. The completed model may be exported in SBML format for additional editing or simulation.
+It is also through the SynBioSS Wiki databases that SynBioSS Designer can access and proliferate kinetic information related to the simulation of BioBricks, thus extending the utility of the database for the benefit of the greater modeling community. To jumpstart the process, we have entered the known biomolecular interactions in the expression and regulation of well-studied operons, such as the lactose, the tetracycline and the arabinose operons.
+==Mathematical Modeling for Team Comparator==
 We will be modeling our system using our in-house software called Synthetic Biology Software Suite (SynBioSS is open source available http://synbioss.sourceforge.net/) and a network of reactions.
 Our first try at the reaction network is shown below.
 {|
-|[[Media:Comparator_Rxn_Network_Model,_Try_1.pdf|First Reaction Network]]
+|[[Media:Comparator_Model_2-1.pdf|First Reaction Network]]
+|}
+{|
+|[[Image:35gfp.jpg|500px|thumb]]
+|-
+|[[Image:35rfp.jpg|500px|thumb]]
+|-
+|[[Image:217GFP.jpg|500px|thumb]]
+|-
+|[[Image:217RFP.jpg|500px|thumb]]
 |}