RESUMEN

The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including fluorescence and sequencing readouts have raised the bar for what it means to quantitatively understand transcriptional regulation. In particular our understanding of the simplest genetic circuit is sufficiently refined both experimentally and theoretically that it has become possible to carefully discriminate between different conceptual pictures of how this regulatory system works. This regulatory motif, originally posited by Jacob and Monod in the 1960s, consists of a single transcriptional repressor binding to a promoter site and inhibiting transcription. In this paper, we show how seven distinct models of this so-called simple-repression motif, based both on thermodynamic and kinetic thinking, can be used to derive the predicted levels of gene expression and shed light on the often surprising past success of the thermodynamic models. These different models are then invoked to confront a variety of different data on mean, variance and full gene expression distributions, illustrating the extent to which such models can and cannot be distinguished, and suggesting a two-state model with a distribution of burst sizes as the most potent of the seven for describing the simple-repression motif.

Asunto(s)

Regulación Bacteriana de la Expresión Génica/genética , Modelos Genéticos , Regiones Promotoras Genéticas/genética , Transcripción Genética/genética , Proteínas Bacterianas/genética , Biología Computacional , Cinética , ARN Bacteriano/genética , ARN Bacteriano/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Termodinámica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo

RESUMEN

Given the stochastic nature of gene expression, genetically identical cells exposed to the same environmental inputs will produce different outputs. This heterogeneity has been hypothesized to have consequences for how cells are able to survive in changing environments. Recent work has explored the use of information theory as a framework to understand the accuracy with which cells can ascertain the state of their surroundings. Yet the predictive power of these approaches is limited and has not been rigorously tested using precision measurements. To that end, we generate a minimal model for a simple genetic circuit in which all parameter values for the model come from independently published data sets. We then predict the information processing capacity of the genetic circuit for a suite of biophysical parameters such as protein copy number and protein-DNA affinity. We compare these parameter-free predictions with an experimental determination of protein expression distributions and the resulting information processing capacity of E. coli cells. We find that our minimal model captures the scaling of the cell-to-cell variability in the data and the inferred information processing capacity of our simple genetic circuit up to a systematic deviation.

Asunto(s)

Redes Reguladoras de Genes , Modelos Genéticos , Escherichia coli/citología , Escherichia coli/genética , Dosificación de Gen

RESUMEN

Membrane transporters carry key metabolites across the cell membrane and, from a resource standpoint, are hypothesized to be produced when necessary. The expression of membrane transporters in metabolic pathways is often upregulated by the transporter substrate. In E. coli, such systems include for example the lacY, araFGH, and xylFGH genes, which encode for lactose, arabinose, and xylose transporters, respectively. As a case study of a minimal system, we build a generalizable physical model of the xapABR genetic circuit, which features a regulatory feedback loop via membrane transport (positive feedback) and enzymatic degradation (negative feedback) of an inducer. Dynamical systems analysis and stochastic simulations show that the membrane transport makes the model system bistable in certain parameter regimes. Thus, it serves as a genetic "on-off" switch, enabling the cell to only produce a set of metabolic enzymes when the corresponding metabolite is present in large amounts. We find that the negative feedback from the degradation enzyme does not significantly disturb the positive feedback from the membrane transporter. We investigate hysteresis in the switching and discuss the role of cooperativity and multiple binding sites in the model circuit. Fundamentally, this work explores how a stable genetic switch for a set of enzymes is obtained from transcriptional auto-activation of a membrane transporter through its substrate.

Asunto(s)

Adaptación Fisiológica/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Redes Reguladoras de Genes , Genes de Cambio , Modelos Biológicos , Sitios de Unión , Transporte Biológico/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Retroalimentación Fisiológica , Regulación Bacteriana de la Expresión Génica , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Pentosiltransferasa/genética , Pentosiltransferasa/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Ribonucleósidos/metabolismo , Procesos Estocásticos , Transactivadores/genética , Transactivadores/metabolismo , Transcripción Genética , Xantinas

RESUMEN

Although initially introduced to mimic the spin-ice pyrochlores, no artificial spin ice has yet exhibited the expected degenerate ice phase with critical correlations similar to the celebrated Coulomb phase in the pyrochlore lattice. Here we study a novel artificial spin ice based on a vertex-frustrated rather than pairwise frustrated geometry and show that it exhibits a quasicritical ice phase of extensive residual entropy and, significantly, algebraic correlations. Interesting in its own regard as a novel realization of frustration in a vertex system, our lattice opens new pathways to study defects in a critical manifold and to design degeneracy in artificial magnetic nanoarrays, a task so far elusive.

RESUMEN

Using cryogenic helium buffer-gas cooling, we have prepared dense samples of atomic lithium and molecular calcium monohydride at temperatures as low as 1 K. We have measured the Li+CaH→LiH+Ca chemical reaction, observed in both the accelerated disappearance of CaH in the presence of high densities of lithium and in the appearance of the LiH molecule.