Team:LCG-UNAM-Mexico/Modelling
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='''Multi-Scale stochastic model for a defense system against Bacteriophage Infection.''' = | ='''Multi-Scale stochastic model for a defense system against Bacteriophage Infection.''' = | ||
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==Contents== | ==Contents== | ||
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###[[Team:LCG-UNAM-Mexico:KZM | Kamikaze Model]] | ###[[Team:LCG-UNAM-Mexico:KZM | Kamikaze Model]] | ||
###[[Team:LCG-UNAM-Mexico:BSD | The Burst Size Distribution]] | ###[[Team:LCG-UNAM-Mexico:BSD | The Burst Size Distribution]] | ||
- | ##[[Team:LCG-UNAM-Mexico:Population | + | ##[[Team:LCG-UNAM-Mexico:Population | Population Scale]]<br> |
###[[Team:LCG-UNAM-Mexico:CA | Multi-Scale integration using Cellular Automata]]<br> | ###[[Team:LCG-UNAM-Mexico:CA | Multi-Scale integration using Cellular Automata]]<br> | ||
- | ###[[Team:LCG-UNAM-Mexico:odes | Mathematical | + | ###[[Team:LCG-UNAM-Mexico:odes | Mathematical Modelling using Delay Differential Equations ]]<br> |
###[[Team:LCG-UNAM-Mexico:ABmodel | Agent Based Simulation Applet]] | ###[[Team:LCG-UNAM-Mexico:ABmodel | Agent Based Simulation Applet]] | ||
</span> | </span> | ||
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==''Summary : Modelling the Defense System''== | ==''Summary : Modelling the Defense System''== | ||
+ | [[Image:Modelling_Diagram.png|480px|thumb|right|'''Logic diagram of our multi-scale stochastic model''']] | ||
Bacteriophage infection is a complicated process, once the virus has infected it steals the translation machinery of its host. Bacterium ribosomes synthesize virus proteins and virus assembly takes place. Beyond a phage and time threshold bacterium can’t take it anymore and explodes setting free the newly synthesized bacteriophages. | Bacteriophage infection is a complicated process, once the virus has infected it steals the translation machinery of its host. Bacterium ribosomes synthesize virus proteins and virus assembly takes place. Beyond a phage and time threshold bacterium can’t take it anymore and explodes setting free the newly synthesized bacteriophages. | ||
Let’s take a look at the big picture: biochemical reactions taking place inside infected bacterium, new synthesized phage for each infected bacterium, other bacteria get infected, infection propagation. We need to approach this problem in a multi-scale fashion: molecular scale and population scale. | Let’s take a look at the big picture: biochemical reactions taking place inside infected bacterium, new synthesized phage for each infected bacterium, other bacteria get infected, infection propagation. We need to approach this problem in a multi-scale fashion: molecular scale and population scale. | ||
We designed and implemented a [[Team:LCG-UNAM-Mexico:Molecular_model| Stochastic Molecular Model]] for the essential reactions involved in the infection process: T7’s DNA insertion, transcription, translation, capsid assembly, etc. to create a Wild Type Simulation. Then we added the toxins to the model to simulate the dynamics of the kamikaze system.<br><br> | We designed and implemented a [[Team:LCG-UNAM-Mexico:Molecular_model| Stochastic Molecular Model]] for the essential reactions involved in the infection process: T7’s DNA insertion, transcription, translation, capsid assembly, etc. to create a Wild Type Simulation. Then we added the toxins to the model to simulate the dynamics of the kamikaze system.<br><br> | ||
- | With a fairly big number of simulations we are going to generate Probability Distributions for the number of molecules for each metabolite as a function of time. We are particularly interested in the [[Team:LCG-UNAM-Mexico:BSD |Burst-Size Distribution (BSD)]]; the burst-size is the number of phages an infected cell will produce. | + | [[Image:Deterministic_model.png|300px|thumb|left|'''Deterministic Molecular Dynamics Model''']] |
+ | <br><br><br><br>With a fairly big number of simulations we are going to generate Probability Distributions for the number of molecules for each metabolite as a function of time. We are particularly interested in the [[Team:LCG-UNAM-Mexico:BSD |Burst-Size Distribution (BSD)]]; the burst-size is the number of phages an infected cell will produce. | ||
Once we have the BSD we are ready for the Spatial Population Model. The kamikaze system we designed is meant to increase the probability that the population as a whole survive an infection process. We make infected-E. Coli commit suicide for the benefit of the population. In case suicide wasn’t altruistic enough we thought an alarm system might be useful: once a bacterium gets infected it will produce AHL to communicate the message that phages are near, advised bacteria will produce antisense RNA against T7’s DNA polymerase. | Once we have the BSD we are ready for the Spatial Population Model. The kamikaze system we designed is meant to increase the probability that the population as a whole survive an infection process. We make infected-E. Coli commit suicide for the benefit of the population. In case suicide wasn’t altruistic enough we thought an alarm system might be useful: once a bacterium gets infected it will produce AHL to communicate the message that phages are near, advised bacteria will produce antisense RNA against T7’s DNA polymerase. | ||
- | To simulate the population scale dynamics we used two different approaches:<br> | + | |
+ | To simulate the population scale dynamics we used two different approaches:<br><br><br><br><br> | ||
We solved the a [[Team:LCG-UNAM-Mexico:odes| system of Delay Differential Equations (DDE’s)]] described in [[Team:LCG-UNAM-Mexico:odes#References | Beretta (2001)]] and We designed and implemented a [[Team:LCG-UNAM-Mexico:CA | Cellular Automaton (CA)]] to approach the spatial dynamics. | We solved the a [[Team:LCG-UNAM-Mexico:odes| system of Delay Differential Equations (DDE’s)]] described in [[Team:LCG-UNAM-Mexico:odes#References | Beretta (2001)]] and We designed and implemented a [[Team:LCG-UNAM-Mexico:CA | Cellular Automaton (CA)]] to approach the spatial dynamics. | ||
- | Using the [[Team:LCG-UNAM-Mexico:CA | CA]] we simulate:<br><br> | + | Using the [[Team:LCG-UNAM-Mexico:CA | CA]] we simulate:<br><br><br> |
* a) ''' Bacteria’s duplication, movement, infection and lysis. | * a) ''' Bacteria’s duplication, movement, infection and lysis. | ||
* b) Quorum Sensing and T7 Diffusion. | * b) Quorum Sensing and T7 Diffusion. | ||
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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. | 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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+ | ---- | ||
+ | <center>[[Team:LCG-UNAM-Mexico:ABmodel |'''Try our applet''']]</center> | ||
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+ | ---- | ||
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==Motivation== | ==Motivation== | ||
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+ | Some bacteriophages are parasites of bacteria, and as such, must prudently exploit their resources (in this case bacteria) to avoid killing bacterium before reproduce enough copies of itself. It has been suggested that parasites have evolved to tune their degree of virulence (amount of damage the parasite causes to the host) to achieve a balance between rapid reproduction and a prudent use of resources [[Team:LCG-UNAM-Mexico:odes#References | [1]]]. It is this fine balance which we intend to break, increasing the virulence of phage in such a way that kills the bacterium so fast that the phage is unable to assemble their own copies.<br><br> | ||
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Bacteria-phage interaction essentially is a fight for survival between two populations. | Bacteria-phage interaction essentially is a fight for survival between two populations. | ||
Although we modified ''E. coli'' at the molecular level to prevent the replication of T7 and T3 , our ultimate goal is that ''E. coli'' can contend against infection at population level. | Although we modified ''E. coli'' at the molecular level to prevent the replication of T7 and T3 , our ultimate goal is that ''E. coli'' can contend against infection at population level. |
Latest revision as of 03:13, 22 October 2009