Team:LCG-UNAM-Mexico

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='''The Project in a nutshell'''=
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Bacteriophage infection represents an interesting process in microbiology and industry. The idea of being able to contend at a population level with such infections is the main motivation for the development of our project.<br>
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We propose a population level approach relaying on a defense system delivered by an engineered version of the enterobacteria phage P4. The purpose of the defense construction is to modify bacteria in order to hold back the process of infection by triggering a cellular death response when a cell encounters a specific component of the infective phage. Such response will be fast enough to stop the formation process of viral particles, thus preventing the phage proliferation and population decline.<br>
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<H3>About Us</h3><br>
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Hi, welcome to our site!  We are students from the undergraduate program in Genomic Sciences which is part of the National Autonomous University of Mexico. We are working on the official version of the wiki. Here you will find advances and general information about our project.<br> Here are some links:<br><br><a href='www.lcg.unam.mx'>LCG web site</a><br><a href='www.ccg.unam.mx'>Center For Genomic Sciences</a><br><a href='www.unam.mx'>UNAM</a><br>
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The delivery system takes advantage of the satellite properties of P4 phage. This means that a P4 phage engineered with the defense construction will be able to infect an ''E.coli'' strain which harbors some genes from helper phage P2 that are used for complementing and completing P4 life cycle, hence creating a production line of our version of P4.<br>
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Besides, the defense system will consist of DNA and RNA degradation by toxins which will be transcribed by T3 or T7 RNA-Polymerases fast enough to stop phage assembly and scattering in the environment. Simultaneously, a quorum sensing signal will be diffusing to the non-infected bacteria acting as a transcriptional activator of an antisense RNA against bacteriophage's transcriptional machinery , hence "warning" the population to prepare against further T3 or T7 infection.<br>
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<br>
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We implemented a stochastic [[Team:LCG-UNAM-Mexico: | multi-scale model]]. The model will simulate the behaviour at the intracellular scale using [[Team:LCG-UNAM-Mexico:Molecular model | stochastic molecular simulations]] and at the populations scale using a [[Team:LCG-UNAM-Mexico:CA | Cellular Automata]] and a [[Team:LCG-UNAM-Mexico:odes | system of ODE's]]. <br> Simulations results are in good agreement with existing experimental data. Thanks to the structure and design of the model this can be easily modified in order to simulate infection dynamics for different bacteria and phages. Furthermore, our Molecular model can be used as a reliable tool for sampling biomolecules distributions involved in phage infection processes. <br>
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<h3>Our Project</h3>
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Bacteriophage infection represents a major problem in the industry and
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research fields. The idea of being able to contend at a population
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level with such infections is the main motivation for the development of our
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project. We plan to modify an Escherichia coli phage in order to deliver
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genetic
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material codifying a construction in defense against other phages
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taking advantage of some of the properties they have.
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The purpose of this construction is that a bacterial population can
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manage to fight back the spreading of some phage by triggering on
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a cellular death response when a cell encounters an
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specific component of the phage. Such response will be faster than the
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formation process of viral particles preventing the death of the bacterial
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population. This population resistance can
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be seen as a sort of "vaccine" that will hold back the process of
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infection.
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The design of the delivery system includes the use the P4 phage and
 
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its auxiliary genes present in the P2 helper phage. In the case of the
 
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"vaccine" construct, the cellular death response will be induced by
 
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the presence of T3 or T7 RNA polymerases which will also turn on the
 
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transcription of toxines used for the
 
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degradation of DNA and RNA to stop the phage´s genetic material from
 
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assembling and scattering in the environment. Furthermore, we will
 
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implement a stochastic population model based on the basic properties
 
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of the bacterial cells and the phages such as movement, reproduction,
 
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etc., that will allow us to simulate the infection processes and
 
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quantify the efficiency of our system. A possible extensión of the
 
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system includes the expansion of  an AHL signal through the quorum
 
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sensing system of Vibrio fischeri in which the population will be
 
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"warned" to prepare against the viral infection in the presence of T3
 
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or T7.
 
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<!--- The Mission, Experiments --->
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{| style="color:#1b2c8a;background-color:#0c6;" cellpadding="3" cellspacing="1" border="1" bordercolor="#fff" width="62%" align="center"
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!align="center"|[[Team:LCG-UNAM-Mexico|Home]]
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!align="center"|[[Team:LCG-UNAM-Mexico/Team|The Team]]
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<header>
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!align="center"|[[Team:LCG-UNAM-Mexico/Project|The Project]]
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!align="center"|[[Team:LCG-UNAM-Mexico/Parts|Parts Submitted to the Registry]]
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!align="center"|[[Team:LCG-UNAM-Mexico/Modeling|Modeling]]
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!align="center"|[[Team:LCG-UNAM-Mexico/Notebook|Notebook]]
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Latest revision as of 01:15, 22 October 2009


The Project in a nutshell

Bacteriophage infection represents an interesting process in microbiology and industry. The idea of being able to contend at a population level with such infections is the main motivation for the development of our project.

We propose a population level approach relaying on a defense system delivered by an engineered version of the enterobacteria phage P4. The purpose of the defense construction is to modify bacteria in order to hold back the process of infection by triggering a cellular death response when a cell encounters a specific component of the infective phage. Such response will be fast enough to stop the formation process of viral particles, thus preventing the phage proliferation and population decline.

The delivery system takes advantage of the satellite properties of P4 phage. This means that a P4 phage engineered with the defense construction will be able to infect an E.coli strain which harbors some genes from helper phage P2 that are used for complementing and completing P4 life cycle, hence creating a production line of our version of P4.
Besides, the defense system will consist of DNA and RNA degradation by toxins which will be transcribed by T3 or T7 RNA-Polymerases fast enough to stop phage assembly and scattering in the environment. Simultaneously, a quorum sensing signal will be diffusing to the non-infected bacteria acting as a transcriptional activator of an antisense RNA against bacteriophage's transcriptional machinery , hence "warning" the population to prepare against further T3 or T7 infection.

We implemented a stochastic multi-scale model. The model will simulate the behaviour at the intracellular scale using stochastic molecular simulations and at the populations scale using a Cellular Automata and a system of ODE's.
Simulations results are in good agreement with existing experimental data. Thanks to the structure and design of the model this can be easily modified in order to simulate infection dynamics for different bacteria and phages. Furthermore, our Molecular model can be used as a reliable tool for sampling biomolecules distributions involved in phage infection processes.












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