Dynamic competition between transcription initiation and repression: Role of nonequilibrium steps in cell-to-cell heterogeneity

Transcriptional repression may cause transcriptional noise by a competition between repressor and RNA polymerase binding. Although promoter activity is often governed by a single limiting step, we argue here that the size of the noise strongly depends on whether this step is the initial equilibrium binding or one of the subsequent unidirectional steps. Overall, we show that nonequilibrium steps of transcription initiation systematically increase the cell-to-cell heterogeneity in bacterial populations. In particular, this allows also weak promoters to give substantial transcriptional noise.Comment: 5 pages, 3 fiugres. Figure and text update

Transición política en Hungría. 1989 - 1990.

Sin resume

EXPERIMENTAL AND NUMERICAL INVESTIGATION INTO NON-ROLLING TYRE

Tyre vibration is an important reason of travell reduction safety when increasing the speed of a vehicle. The tyre circumference can be seen as a loop shaped chain of elastic parts which have their portion of the mass of the tyre. This model is suitable for computer aided investigation on tyre vibration phenomena such as steady waves when rolling. Such an investigation is presented in this article

A Mixed Incoherent Feed-Forward Loop Allows Conditional Regulation of Response Dynamics

Expression of the SodA superoxide dismutase (MnSOD) in Escherichia coli is regulated by superoxide concentration through the SoxRS system and also by Fur (Ferric uptake regulator) through a mixed incoherent feed forward loop (FFL) containing the RyhB small regulatory RNA. In this work I theoretically analyze the function of this feed forward loop as part of the network controlling expression of the two cytoplasmic superoxide dismutases, SodA and SodB. I find that feed forward regulation allows faster response to superoxide stress at low intracellular iron levels compared to iron rich conditions. That is, it can conditionally modulate the response time of a superimposed transcriptional control mechanism

Structure and function of negative feedback loops at the interface of genetic and metabolic networks

The molecular network in an organism consists of transcription/translation regulation, protein-protein interactions/modifications and a metabolic network, together forming a system that allows the cell to respond sensibly to the multiple signal molecules that exist in its environment. A key part of this overall system of molecular regulation is therefore the interface between the genetic and the metabolic network. A motif that occurs very often at this interface is a negative feedback loop used to regulate the level of the signal molecules. In this work we use mathematical models to investigate the steady state and dynamical behaviour of different negative feedback loops. We show, in particular, that feedback loops where the signal molecule does not cause the dissociation of the transcription factor from the DNA respond faster than loops where the molecule acts by sequestering transcription factors off the DNA. We use three examples, the bet, mer and lac systems in E. coli, to illustrate the behaviour of such feedback loops.Comment: 8 pages, 4 figure

Structure and Function of the d-Galactose Network in Enterobacteria

Galactose is important for the survival and virulence of bacteria. In Escherichia coli, galactose is utilized by the Leloir pathway, which is controlled by a complex network. To shed light on the potential functions the galactose network could perform, we performed bioinformatical analysis of reference genome sequences belonging to the Enterobacteriaceae family. We found that several genomes have reduced numbers of components compared to the E. coli galactose system, suggesting that the network can be optimized for different environments. Typically, genes are removed by deletions; however, in Yersinia pestis, the galactose mutarotase (galM) gene is inactivated by a single-base-pair deletion. Lack of GalM activity indicates that the two anomers of d-galactose are used for different purposes, α-d-galactose as a carbon source and β-d-galactose for induction of UDP-galactose synthesis for biosynthetic glycosylation. We demonstrate that activity of the galM gene can be restored by different single-base-pair insertions. During the evolution of Y. pestis to become a vector-transmitted systemic pathogen, many genes were converted to pseudogenes. It is not clear whether pseudogenes are present to maintain meiotrophism or are in the process of elimination. Our results suggest that the galM pseudogene has not been deleted because its reactivation may be beneficial in certain environments

Coupled positive and negative feedbacks produce diverse gene expression patterns in colonies

Formation of patterns is a common feature in the development of multicellular organism as well as of microbial communities. To investigate the formation of gene expression patterns in colonies, we build a mathematical model of two-dimensional colony growth, where cells carry a coupled positive-and-negative-feedback circuit. We demonstrate that the model can produce sectored, target (concentric), uniform, and scattered expression patterns of regulators, depending on gene expression dynamics and nutrient diffusion. We reconstructed the same regulatory structure in Escherichia coli cells and found gene expression patterns on the surface of colonies similar to the ones produced by the computer simulations. By comparing computer simulations and experimental results, we observed that very simple rules of gene expression can yield a spectrum of well-defined patterns in a growing colony. Our results suggest that variations of the protein content among cells lead to a high level of heterogeneity in colonies. Importance Formation of patterns is a common feature in the development of microbial communities. In this work, we show that a simple genetic circuit composed of a positive-feedback loop and a negative-feedback loop can produce diverse expression patterns in colonies. We obtained similar sets of gene expression patterns in the simulations and in the experiments. Because the combination of positive feedback and negative feedback is common in intracellular molecular networks, our results suggest that the protein content of cells is highly diversified in colonies