Section: New Results

Stochastic Modeling of Biological Networks

Participants : Emanuele Leoncini, Philippe Robert.

This is a collaboration with Vincent Fromion from INRA Jouy en Josas, which started on October 2010.

The goal is to propose a mathematical model of the production of proteins in prokaryotes. Proteins are biochemical compounds that play a key role in almost all the cell functions and are crucial for cell survival and for life in general. In bacteria the protein production system has to be capable to produce abut 2500 different types of proteins in different proportions (from few dozens for the replication machinery to more than 100000 for certain key metabolic enzymes). Bacteria uses more than the 85% of their resources to the protein production, making it the most relevant process in these organisms. Moreover this production system must meet two opposing problems: on one side it must provide the minimal proteins quantities in order to ensure the smooth-running of the cell, on the other side it can not choose a “overproduction policy” for all the proteins, since this would impact the global performance of the system and of the bacterium itself.

Gene expression is intrinsically a stochastic process: gene activation/deactivation occurs by means the encounter of polymerase/repressor with the specific gene, moreover many molecules that take part in the protein production act at extremely low concentrations.

We have restated mathematically the classical model using Poisson point processes. This representation, well-known in the field of queueing networks but, as far as we know, new in the gene expression modeling, allowed us to weaken few hypothesis of the existing models, in particular the Poisson hypothesis, which is well-suited in some cases, but that, in some situations, is far from the biological reality as we consider for instance the protein assemblage.

The theoretical environment of Poisson point processes has lead us to propose a new model of gene expression which captures on one side the main mechanisms of the gene expression and on the other side it tries to consider hypothesis that are more significant from a biological viewpoint. In particular we have modeled: gene activation/deactivation, mRNA production and degradation, ribosome attachment on mRNA, protein production and degradation.

We have shown how the probability distribution of the protein production and the protein lifetime may have a significant impact on the fluctuations of the number of proteins. We have obtained analytic formulas when the duration of protein assemblage and degradation follows a general probability distribution, i.e. without the Poisson hypothesis. We have used our model to compare the variances resulting by choosing different hypotheses for the probability distribution of the protein production and degradation, in particular we have hypothesize the protein assembly and degradation to be deterministic. The model has showed how, under the previous hypothesis, the variance on the number of proteins is bigger than the classical model with the Poisson hypothesis.