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Transcription factors (TFs) are proteins that bind to specific sites on the DNA and regulate gene activity. Identifying where TF molecules bind and how much time they spend on their target sites is key for understanding transcriptional…
Gene expression is a readily-observed quantification of transcriptional activity and cellular state that enables the recovery of the relationships between regulators and their target genes. Reconstructing transcriptional regulatory networks…
A wide range of organisms use circadian clocks to keep internal sense of daily time and regulate their behavior accordingly. Most of these clocks use intracellular genetic networks based on positive and negative regulatory elements. The…
Regulatory interactions between genes show a large amount of cross-species variability, even when the underlying functions are conserved: There are many ways to achieve the same function. Here we investigate the ability of regulatory…
Transcription factors (TFs) interact with a multitude of binding sites on DNA and partner proteins inside cells. We investigate how nonspecific binding/unbinding to such decoy binding sites affects the magnitude and time-scale of random…
We model the transcription factor based regulation network of yeast using a content-based network model that mimicks the recognition of binding motifs on the regulatory regions of the genes. We are thereby able to faithfully reproduce many…
Two synthetic gene circuits -- the genetic toggle switch and the repressilator -- are analyzed quantitatively and discussed in the context of an educational module on gene circuits and feedback that constitutes the final topic of a…
Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor,…
Gene expression is a biochemical process, where stochastic binding and un-binding events naturally generate fluctuations and cell-to-cell variability in gene dynamics. These fluctuations typically have destructive consequences for proper…
We introduce simple models of genetic regulatory networks and we proceed to the mathematical analysis of their dynamics. The models are discrete time dynamical systems generated by piecewise affine contracting mappings whose variables…
We present an approach for constructing dynamic models for the simulation of gene regulatory networks from simple computational elements. Each element is called a ``gene gate'' and defines an input/output-relationship corresponding to the…
Genetic oscillators play important roles in cell life regulation. The regulatory efficiency usually depends strongly on the emergence of stable collective dynamic modes, which requires designing the interactions between genetic networks. We…
The regulatory mechanisms driving progression of the yeast cell cycle appears to be comprised of an interacting network of transcription factors (TFs), cyclin-dependent kinases (CDK) and ubiquitin ligases. From a systems perspective the…
The transient response to a stimulus and subsequent recovery to a steady state are the fundamental characteristics of a living organism. Here we study the relaxation kinetics of autoregulatory gene networks based on the chemical master…
The impact of random fluctuations on the dynamical behavior a complex biological systems is a longstanding issue, whose understanding would shed light on the evolutionary pressure that nature imposes on the intrinsic noise levels and would…
According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell…
Changes in a cell's external or internal conditions are usually reflected in the concentrations of the relevant transcription factors. These proteins in turn modulate the expression levels of the genes under their control and sometimes need…
In 2000, Elowitz and Leibler introduced the repressilator--a synthetic gene circuit with three genes that cyclically repress transcription of the next gene--as well as a corresponding mathematical model. Experimental data and model…
A prominent feature of gene transcription regulatory networks is the presence in large numbers of motifs, i.e, patterns of interconnection, in the networks. One such motif is the feed forward loop (FFL) consisting of three genes X, Y and Z.…
From the response to external stimuli to cell division and death, the dynamics of living cells is based on the expression of specific genes at specific times. The decision when to express a gene is implemented by the binding and unbinding…