Related papers: Dynamics of transcription factor binding site evol…
A transversal topic of my research has been the development and application of computational methods for DNA sequence analysis. The methods I have been developing aim at improving our understanding of the regulation processes happening in…
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,…
In unicellular organisms such as bacteria the same acquired mutations beneficial in one environment can be restrictive in another. However, evolving Escherichia coli populations demonstrate remarkable flexibility in adaptation. The…
Genetic circuits need a cellular environment to operate in, which naturally couples the circuit function with the overall functionality of gene regulatory network. To execute their functions all gene circuits draw resources in the form of…
Cells coordinate adjustments in genome expression to accommodate changes in their environment. A drug in culture media for in vitro preclinical testing sometimes cause drastic regime shifting of genome expression system depending on the…
Models of transcriptional regulation that assume equilibrium binding of transcription factors have been very successful at predicting gene expression from sequence in bacteria. However, analogous equilibrium models do not perform as well in…
DNA looping participates in transcriptional regulation, for instance, by allowing distal binding sites to act synergistically. Here we study this process and compare different regulatory mechanisms based on repression with and without…
Large sets of genotypes give rise to the same phenotype because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as thegenotype mutates into another one on the…
In the course of various biological processes, specific DNA-binding proteins must find a particular target sequence/protein or a damaged site on the DNA efficiently. DNA-binding proteins perform this task based on diffusion. Yet,…
Under constant selection, each trait has a fixed fitness, and small mutation rates allow populations to efficiently exploit the optimal trait. Therefore it is reasonable to expect mutation rates will evolve downwards. However, we find this…
Gene regulation involves a hierarchy of events that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. The effects of DNA sequence on these processes have typically been studied based…
In early development, regulation of transcription results in precisely positioned and highly reproducible expression patterns that specify cellular identities. How transcription, a fundamentally noisy molecular process, is regulated to…
Gene transcription is a stochastic process that involves thousands of reactions. The first set of these reactions, which happen near a gene promoter, are considered to be the most important in the context of stochastic noise. The most…
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…
Genetic variation affecting gene regulation is a central driver of phenotypic differences between individuals and can be used to uncover how biological processes are organized in a cell. Although detecting cis-eQTLs is now routine,…
Cells integrate signals and make decisions about their future state in short amounts of time. A lot of theoretical effort has gone into asking how to best design gene regulatory circuits that fulfill a given function, yet little is known…
Understanding how transcription factors (TFs) regulate mammalian gene expression in space and time is a central topic in biology. To activate a gene, a TF has first to diffuse in the available space of the nucleus until it reaches a target…
Riboswitches, structured elements in the untranslated regions of messenger RNAs, regulate gene expression by binding specific metabolites. We introduce a kinetic network model that describes the functions of riboswitches at the systems…
Recent work has shown that expression level is the main predictor of a gene’s evolutionary rate, and that more highly expressed genes evolve slower. A possible explanation for this observation is selection for proteins which fold…
Delay is an inherent feature of genetic regulatory networks. It represents the time required for the assembly of functional regulator proteins. The protein production process is complex, as it includes transcription, translocation,…