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Gene regulation in higher eukaryotes involves a complex interplay between the gene proximal promoter and distal genomic elements (such as enhancers) which work in concert to drive spatio-temporal expression. The experimental…
In this paper we study an important global regulation mechanism of transcription of biological cells using specific macro-molecules, 6S RNAs. The functional property of 6S RNAs is of blocking the transcription of RNAs when the environment…
Considerable evidence suggests that anticipating sudden shifts from one state to another in bistable dynamical systems is a challenging task, examples include ecosystems, financial markets, complex diseases, etc. In this paper, we…
Pluripotent embryonic stem cells are of paramount importance for biomedical research thanks to their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent…
In this paper, we consider two stochastic models of gene expression in prokaryotic cells. In the first model, sixteen biochemical reactions involved in transcription, translation and transcriptional regulation in the presence of inducer…
Transcription factor binding sites vary in their specificity, both within and between species. Binding specificity has a strong impact on the evolution of gene expression, because it determines how easily regulatory interactions are gained…
We show how one may analytically compute the stationary density of the distribution of molecular constituents in populations of cells in the presence of noise arising from either bursting transcription or translation, or noise in…
Regulatory networks describe the interactions between molecular or cellular regulators, like transcription factors and genes in gene regulatory networks, kinases and their receptors in signalling networks, or neurons in neural networks. A…
Mathematical models of stem cell differentiation are commonly based upon the concept of subsequent cell fate decisions, each controlled by a gene regulatory network. These networks exhibit a multistable behavior and cause the system to…
During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signaling molecules - morphogens - guide this process. The continuous positional information…
Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of…
In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be…
Transcription commonly occurs in bursts, with alternating productive (ON) and quiescent (OFF) periods, governing mRNA production rates. Yet, how transcription is regulated through bursting dynamics remains unresolved. Here, we conduct…
We consider the dynamics of a population of organisms containing two mutually inhibitory gene regulatory networks, that can result in a bistable switch-like behaviour. We completely characterize their local and global dynamics in the…
Even under constant external conditions, the expression levels of genes fluctuate. Much emphasis has been placed on the components of this noise that are due to randomness in transcription and translation; here we analyze the role of noise…
Mathematical models of gene regulatory networks are widely used to study cell fate changes and transcriptional regulation. When designing such models, it is important to accurately account for sources of stochasticity. However, doing so can…
Cells receive a wide variety of cellular and environmental signals, which must be processed combinatorially to generate specific and timely genetic responses. We present here a theoretical study on the combinatorial control and integration…
Cell-fate transition can be modeled by ordinary differential equations (ODEs) which describe the behavior of several molecules in interaction, and for which each stable equilibrium corresponds to a possible phenotype (or 'biological…
Auto-regulatory feedback loops are one of the most common network motifs. A wide variety of stochastic models have been constructed to understand how the fluctuations in protein numbers in these loops are influenced by the kinetic…
Genetic switch systems with mutual repression of two transcription factors are studied using deterministic methods (rate equations) and stochastic methods (the master equation and Monte Carlo simulations). These systems exhibit bistability,…