Team:LCG-UNAM-Mexico:BSD

From 2009.igem.org

(Difference between revisions)
Line 62: Line 62:
<br><br><br><br><br><br><br><br><br><br><br><br>
<br><br><br><br><br><br><br><br><br><br><br><br>
===Sensitivity Analysis for T7 mRNA half-life===
===Sensitivity Analysis for T7 mRNA half-life===
-
<br><br>
+
<br>
 +
----
 +
<br>
 +
Previous intracellar simulations for bacteriophage devolpment didn't take into account the half-life of the phage mRNA.
 +
To answer the question of whether this parameter affects the Burst Size or not, we implemented a sensitivity analysis.
 +
The average half-life reported for early T7 messengers is 6.5 min. []
 +
 
 +
<br>
[[Image:BSD_degradation2.jpg|thumb|300px|right|alt=Sensitivity Analysis for T7 mRNA average lifetime|Sensitivity analysis for the T7 mRNA half-life. For each value of the parameter we performed 1000 simulations of the molecular model and the mean was computed. Standard deviation bars are shown.  .]]
[[Image:BSD_degradation2.jpg|thumb|300px|right|alt=Sensitivity Analysis for T7 mRNA average lifetime|Sensitivity analysis for the T7 mRNA half-life. For each value of the parameter we performed 1000 simulations of the molecular model and the mean was computed. Standard deviation bars are shown.  .]]
Line 78: Line 85:
#De Paepe. Viruses Life History: Towards a Mechanistic Basis of a Trade-Off between Survival and Reproduction among Phage. 2006.<br>
#De Paepe. Viruses Life History: Towards a Mechanistic Basis of a Trade-Off between Survival and Reproduction among Phage. 2006.<br>
#Paul D. Sadowski. Suppression of a Mutation in Gene 3  of Bacteriophage T7 (T7 Endonuclease) by Mutations in Phage and Host Polynucleotide Ligase. 1973<br>
#Paul D. Sadowski. Suppression of a Mutation in Gene 3  of Bacteriophage T7 (T7 Endonuclease) by Mutations in Phage and Host Polynucleotide Ligase. 1973<br>
 +
#Yamada. Chemical Stability of Bacteriophage T7 Early mRNA. 1975

Revision as of 12:54, 21 October 2009


The Burst-Size Distribution


Content



The Burst Size Distribution


In 1939 Ellis and Delbrück obtained values which indicated an exceedingly wide variation of the burst sizes for different bacteriophages. In 1945 Delbrück published the first Burst-Size distribution using an improved technique for bacteriophage T1.

The reported values for the burst size of T7 are in the range 100-300, this values are used in many population models for bacteriophage infection [][][].

It is important to have a reliable simulation of the intracellular dynamics in order to generate values for the burst-size. Creating a Burst-Size distribution is one of the most important things of our work since it will be the link between the intracellular scale and the population scale simulations. The BSD is by no means the only distributions generated by our intracellular simulations, distributions for each species in the model are generated indeed.



T7 Reported Burst Size
WT Measured T7 BS Reference
266±16 Heineman 2007
130±50 Stanley 1989
260 De Paepe 2006
214 Sadowski 1973
300 Brock 1990}

Table1.Experimentally measured T7 Burst Size





Simulated BSD



Burst Size Distribution
Burst Size Distribution obtained from the simulation Results of the Molecular Simulations.




Without defence system our simulated BSD has mean 176 and standard deviation 102. This distribution was created running 1000 simulations of the intracellular model.
We see that experimentally measured values fall within this distribution. The large variance seen by Delbrück and the dispersion in experimental values is congruent with our results (table 1).
Dispersion in our simulations its due only to stochastic fluctuations in ocurrence of chemical reactions.

So using our model we can sample distributions for any of the biochemical species in the system and use those values to assemble more complex stochastic models as we did with the Cellular Automata.













Sensitivity Analysis for T7 mRNA half-life



Previous intracellar simulations for bacteriophage devolpment didn't take into account the half-life of the phage mRNA. To answer the question of whether this parameter affects the Burst Size or not, we implemented a sensitivity analysis. The average half-life reported for early T7 messengers is 6.5 min. []


Sensitivity Analysis for T7 mRNA average lifetime
Sensitivity analysis for the T7 mRNA half-life. For each value of the parameter we performed 1000 simulations of the molecular model and the mean was computed. Standard deviation bars are shown. .




















BSD using the Defense System




References



  1. Thomas D. Brock. Emergence of Bacterial Genetics, 1990.
  2. Delbrück. Burst Size Distribution in the Growth of Bacterial Viruses(Bacteriophages). 1945
  3. Richard H. Heineman and James J. Bull . Testing Optimality with experimental evolution: Lysis Time in time . 2007
  4. De Paepe. Viruses Life History: Towards a Mechanistic Basis of a Trade-Off between Survival and Reproduction among Phage. 2006.
  5. Paul D. Sadowski. Suppression of a Mutation in Gene 3 of Bacteriophage T7 (T7 Endonuclease) by Mutations in Phage and Host Polynucleotide Ligase. 1973
  6. Yamada. Chemical Stability of Bacteriophage T7 Early mRNA. 1975
Retrieved from "http://2009.igem.org/Team:LCG-UNAM-Mexico:BSD"