From 2009.igem.org
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| + | Bacteria play a fundamental role in human life. They are still the preferred models in science for the study of the molecular dynamics of organisms; probiotics are of vital importance in industry and food manufacturing. Infection by phages represents a relevant and expensive problem. That is the reason why we decided to construct a system to contend bacteriophage infection.<br> |
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- | Bacteriophage infection represents an interesting process in science 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>
| + | Using a population approach makes feasible to achieve a faster and wider protection response by amplifying the infection signal of the delivery phage in order to increase the number of "immune" bacteria at every lytic cycle.<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 make a bacteria 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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- | Delivery of the defense system take 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 the 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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- | On the other hand 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 difunding to the non-infected bacterias 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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- | Furthermore, we will implement 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>
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| + | The idea for structuring our project on two subsystems emerges from this global protection vision. The coupled expression of the subsystems leads to a cascade dependent on the presence of an infectious phage. This property gives an extra versatility to our project because the defense turns on fast enough to hold back infection and remains enough to give immunity to the population.<br> |
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| =='''Design'''== | | =='''Design'''== |
Revision as of 02:25, 20 October 2009