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God does not throw dice – but do bacteria?

Many properties of any living being are encoded in its genetic material. This includes the species of an organism, but also many aspects of its appearance: For instance the color of the human eye is encoded in the DNA.

Even for identical twins having the very same genetic material, there exist physical differences which are manifested for example in liver spots or fingerprints. In this context one distinguishes identical genotype (same genes) from different phenotype (distinct appearance). This is caused by the combination of active genes which actually trigger the production of proteins. Interestingly, which genes are active depends not only on past and present environmental influences but also on random fluctuations. For single celled organisms such as bacteria, the impact of phenotypes is much more pronounced: Depending on availability of nutrients, competition with other cells and further environmental conditions, they can adapt their metabolism, release antibiotics or react in another manner.

The soil-dwelling bacterium Bacillus subtilis reacts in a particularly interesting way to nutrient deprivation and excess of population: Though being genetically identical, about 15% of all individuals acquire the ability to take up genetic material from the surrounding medium. This property is called „competence“. Competent cells have a higher probability to take up alien (and potentially useful) genes and thereby ensure survival of the species. However, alien genes can also be harmful and much energy has to be invested in producing the proteins necessary for competence. Keeping this in mind it is quite reasonable to have only a fraction of the population becoming competent. This raises some crucial question: What determines which fraction of the cells in the population should become competent? How is switching to the competent phenotype triggered in a single bacterium?

 

 

Picture: © Biophysical Journal, 96, 3 (2009)

Figure: Bacteria exhibiting the competent phenotype express a fluorescent protein. Characteristics of competence development can be attained from the time-dependent fluorescence intensity.
A simplified gene-regulatory network for competence emergence is given. Mathematical modeling yields equations for the evolution of the key competence protein (K) and the corresponding mRNA (M).
Analysis of the model (red and blue lines) predicts stable phenotypes, while computer simulations (black line) show how switching between phenotypes is achieved. Simulation and experiments show excellent agreement.

 

 

 

To answer these questions, Madeleine Leisner and Jan-Timm Kuhr from the International Doctorate Program NanoBioTechnology, followed the transformation of phenotype in single cell experiments and compared the results with a theoretical model. According to this, a high cell density increases the probability to activate self-enhancing production of the key competence protein. However, in which bacterium this happens is determined by random fluctuations in the number of corresponding mRNA molecules. A time window, during which fluctuations are sufficiently strong to permit startup of protein production, sets the relative fraction of the total population.
The non-linear model of this cooperative project predicts the fraction of competent cells and the time to switch between phenotypes. Furthermore, the model makes the process more comprehensible in an intuitive way and fully explains additional experiments, in which all bacteria acquire competence.

This collaboration of PhD students from experimental and theoretical biophysics describes new experimental methods, a theoretical model and stochastic simulations. These approaches were employed to investigate in the switching between phenotypes and elucidate the underlying mechanism.

 

Publication:
"Kinetics of Genetic Switching into the State of Bacterial Competence"
M. Leisner, J. Kuhr, J. O. Rädler, E. Frey, B. Maier
Biophysical Journal, 96, 3 (2009)

Madeleine Leisner
Education

since 2008
Postdoctoral research at Harvard University, USA

2004 - 2008
Doctoral Thesis,
Supervisor: Prof. Joachim Rädler, LMU Munich

1999 - 2004
Diploma in biology, University of Regensburg, Germany

Selected Publication

Leisner et al.:
"Basal expression rate of comK sets a "switching-window" into the K-stat of Bacillus subtilis"

Mol. Microbiol, 63(6) 1806-1816 (2007)

Jan-Timm Kuhr
Education

since 2009
PhD candidate in the group of
Prof. Erwin Frey, LMU Munich

1999 - 2006
Diploma in Physics, LMU Munich

2001 - 2002
Studies of Physics at the University of Nottingham

Selected Publication

M. Leisner, J. Kuhr, J. O. Rädler, E. Frey, B. Maier:
"Kinetics of Genetic Switching into the State of Bacterial Competence"
Biophysical Journal, 96, 3 (2009)