In Silico Biology - Volume 12, issue 1,2

Authors: Bray, Dennis

Article Type: Research Article

Abstract: Are we close to a complete inventory of living processes so that we might expect in the near future to reproduce every essential aspect necessary for life? Or are there mechanisms and processes in cells and organisms that are presently inaccessible to us? Here I argue that a close examination of a particularly well-understood system— that of Escherichia coli chemotaxis— shows we are still a long way from a complete description. There is a level of molecular uncertainty, particularly that responsible for fine-tuning and adaptation to myriad external conditions, which we presently cannot resolve or reproduce on a computer. …Moreover, the same uncertainty exists for any process in any organism and is especially pronounced and important in higher animals such as humans. Embryonic development, tissue homeostasis, immune recognition, memory formation, and survival in the real world, all depend on vast numbers of subtle variations in cell chemistry most of which are presently unknown or only poorly characterized. Overcoming these limitations will require us to not only accumulate large quantities of highly detailed data but also develop new computational methods able to recapitulate the massively parallel processing of living cells. Show more

DOI: 10.3233/ISB-140461

Citation: In Silico Biology, vol. 12, no. 1,2, pp. 1-7, 2012

Authors: Gupta, Abhishekh | Lloyd-Price, Jason | Ribeiro, Andre S.

Article Type: Research Article

Abstract: Recent evidence suggests that cells employ functionally asymmetric partitioning schemes in division to cope with aging. We explore various schemes in silico , with a stochastic model of Escherichia coli that includes gene expression, non-functional proteins generation, aggregation and polar retention, and molecule partitioning in division. The model is implemented in SGNS2, which allows stochastic, multi-delayed reactions within hierarchical, transient, interlinked compartments. After setting parameter values of non-functional proteins’ generation and effects that reproduce realistic intracellular and population dynamics, we investigate how the spatial organization of non-functional proteins affects mean division times of cell populations in lineages and, thus, …mean cell numbers over time. We find that division times decrease for increasingly asymmetric partitioning. Also, increasing the clustering of non-functional proteins decreases division times. Increasing the bias in polar segregation further decreases division times, particularly if the bias favors the older pole and aggregates’ polar retention is robust. Finally, we show that the non-energy consuming retention of inherited non-functional proteins at the older pole via nucleoid occlusion is a source of functional asymmetries and, thus, is advantageous. Our results suggest that the mechanisms of intracellular organization of non-functional proteins, including clustering and polar retention, affect the vitality of E. coli populations. Show more

Keywords: Non-functional proteins, partitioning schemes, functional asymmetries, division times, In silico models

DOI: 10.3233/ISB-140462

Citation: In Silico Biology, vol. 12, no. 1,2, pp. 9-21, 2012

Authors: Mackey, Michael C. | Santillán, Moisés | Tyran-Kamińska, Marta | Zeron, Eduardo S.

Article Type: Research Article

Abstract: In this review, we survey work that has been carried out in the attempts of biomathematicians to understand the dynamic behaviour of simple bacterial operons starting with the initial work of the 1960’s. We concentrate on the simplest of situations, discussing both repressible and inducible systems and then turning to concrete examples related to the biology of the lactose and tryptophan operons. We conclude with a brief discussion of the role of both extrinsic noise and so-called intrinsic noise in the form of translational and/or transcriptional bursting.

DOI: 10.3233/ISB-140463

Citation: In Silico Biology, vol. 12, no. 1,2, pp. 23-53, 2012

Authors: Ingalls, Brian P. | Bembenek, Eric

Article Type: Research Article

Abstract: Analysis of metabolic networks typically begins with construction of the stoichiometry matrix, which characterizes the network topology. This matrix provides, via the balance equation, a description of the potential steady-state flow distribution. This paper begins with the observation that the balance equation depends only on the structure of linear redundancies in the network, and so can be stated in a succinct manner, leading to computational efficiencies in steady-state analysis. This alternative description of steady-state behaviour is then used to provide a novel method for network reduction, which complements existing algorithms for describing intracellular networks in terms of input-output macro-reactions (to …facilitate bioprocess optimization and control). Finally, it is demonstrated that this novel reduction method can be used to address elementary mode analysis of large networks: the modes supported by a reduced network can capture the input-output modes of a metabolic module with significantly reduced computational effort. Show more

Keywords: Metabolic network, metabolic flux analysis, metabolic control analysis, network reduction, metabolic module, elementary flux modes

DOI: 10.3233/ISB-140464

Citation: In Silico Biology, vol. 12, no. 1,2, pp. 55-67, 2012

Authors: Zamora-Chimal, CG | Zeron, ES

Article Type: Research Article

Abstract: We develop an exact and flexible mathematical model for Lutz and Bujard’s controllable promoters. It can be used as a building block for modeling genetic systems based on them. Special attention is paid to deduce all the model parameters from reported (in vitro ) experimental data. We validate our model by comparing the regulatory ranges measured in vivo by Lutz and Bujard against the ranges predicted by the model, and which are calculated as the reporter activity obtained under inducing conditions divided by the activity measured under maximal repression. In particular, we verify Bond et al. assertion that the cooperativity …between two lac operators can be assumed to be negligible when their central base pairs are separated by 22 or 32 bp [Gene repression by minimal lac loops in vivo , Nucleic Acids Res, 38 (2010) 8072–8082]. Moreover, we also find that the probability that two repressors LacI bind to these operators at the same time can be assumed to be negligible as well. We finally use the model for the promoter P LlacO -1 to analyze a synthetic genetic oscillator recently build by Stricker et al. [A fast, robust and tunable synthetic gene oscillator, Nature, 456 (2008) 516–519]. Show more

Keywords: Synthetic promoters, lac and tet operators, biochemical oscillations

DOI: 10.3233/ISB-150465

Citation: In Silico Biology, vol. 12, no. 1,2, pp. 69-82, 2012