Daniel A. Charlebois

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We show that the effect of stress on the reproductive fitness of noisy cell populations can be modeled as a first-passage time problem, and demonstrate that even relatively short-lived fluctuations in gene expression can ensure the long-term survival of a drug-resistant population. We examine how this effect contributes to the development of drug-resistant(More)
We present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics. The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a constant-number Monte Carlo method to simulate time-dependent statistical characteristics of growing cell populations. To benchmark performance,(More)
Fluctuations in gene expression give identical cells access to a spectrum of phenotypes that can serve as a transient, nongenetic basis for natural selection by temporarily increasing drug resistance. In this study, we demonstrate using mathematical modeling and simulation that certain gene regulatory network motifs, specifically coherent feedforward loop(More)
UNLABELLED We present CellLine, a simulator of the dynamics of gene regulatory networks (GRN) in the cells of a lineage. From user-defined reactions and initial substance quantities, it generates cell lineages, i.e. genealogic pedigrees of cells related through mitotic division. Each cell's dynamics is driven by a delayed stochastic simulation algorithm(More)
The appearance of microarray technology led to the development of algorithms to infer the structure underlying the dynamics of gene regulatory networks (GRNs) from gene expression data. Yet, this technique is currently highly noisy, leading to the question of how inferable are GRNs from this data. To answer this question, we use realistic models of GRNs [1,(More)
The benefits of “bet-hedging” strategies have been assumed to be the main cause of phenotypic diversity in biological populations. However, in their recent work, Healey et al (2016) provide experimental support for negative frequency-dependent selection (NFDS) as an alternative driving force of diversity. NFDS favors rare phenotypes over common ones,(More)
Synthetic biology aims to design new biological systems for predefined purposes, such as the controlled secretion of biofuels, pharmaceuticals, or other chemicals. Synthetic gene circuits regulating an efflux pump from the ATP-binding cassette (ABC) protein family could achieve this. However, ABC efflux pumps can also drive out intracellular inducer(More)
Gene expression is a stochastic process that affects cellular and population fitness. Noise in gene expression can enhance fitness by increasing cell to cell variability as well as the time cells spend in favorable expression states. Using a stochastic model of gene expression together with a fitness function that incorporates the costs and benefits of gene(More)
Here we present a complete description of the example models that we tested and the results we obtained using CellLine. We also provide all reactions files (see Availability section). To demonstrate the use of CellLine, we first simulate a model of the P53-Mdm2 feedback loop, where transcription and translation are modelled by multiple time delayed(More)
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