scholarly journals Ecological feedback in quorum-sensing microbial populations can induce heterogeneous production of autoinducers

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Matthias Bauer ◽  
Johannes Knebel ◽  
Matthias Lechner ◽  
Peter Pickl ◽  
Erwin Frey
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Promoter Activity ◽  
Phenotypic Heterogeneity ◽  
Microbial Populations ◽  
Alternative Mechanism ◽  
Stochastic Gene Expression ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

Autoinducers are small signaling molecules that mediate intercellular communication in microbial populations and trigger coordinated gene expression via ‘quorum sensing’. Elucidating the mechanisms that control autoinducer production is, thus, pertinent to understanding collective microbial behavior, such as virulence and bioluminescence. Recent experiments have shown a heterogeneous promoter activity of autoinducer synthase genes, suggesting that some of the isogenic cells in a population might produce autoinducers, whereas others might not. However, the mechanism underlying this phenotypic heterogeneity in quorum-sensing microbial populations has remained elusive. In our theoretical model, cells synthesize and secrete autoinducers into the environment, up-regulate their production in this self-shaped environment, and non-producers replicate faster than producers. We show that the coupling between ecological and population dynamics through quorum sensing can induce phenotypic heterogeneity in microbial populations, suggesting an alternative mechanism to stochastic gene expression in bistable gene regulatory circuits.

scholarly journals Variation, Variegation and Heritable Gene Repression in S. cerevisiae

2021 ◽  
Vol 12 ◽  
Author(s):  
Kholoud Shaban ◽  
Safia Mahabub Sauty ◽  
Krassimir Yankulov
Keyword(s):  
Gene Expression ◽  
Current Knowledge ◽  
Regulatory Circuits ◽  
Epigenetic Diversity ◽  
Short And Long Term ◽  
Unstructured Proteins ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits ◽  
Insight Into

Phenotypic heterogeneity provides growth advantages for a population upon changes of the environment. In S. cerevisiae, such heterogeneity has been observed as “on/off” states in the expression of individual genes in individual cells. These variations can persist for a limited or extended number of mitotic divisions. Such traits are known to be mediated by heritable chromatin structures, by the mitotic transmission of transcription factors involved in gene regulatory circuits or by the cytoplasmic partition of prions or other unstructured proteins. The significance of such epigenetic diversity is obvious, however, we have limited insight into the mechanisms that generate it. In this review, we summarize the current knowledge of epigenetically maintained heterogeneity of gene expression and point out similarities and converging points between different mechanisms. We discuss how the sharing of limiting repression or activation factors can contribute to cell-to-cell variations in gene expression and to the coordination between short- and long- term epigenetic strategies. Finally, we discuss the implications of such variations and strategies in adaptation and aging.

scholarly journals Gene Circuit Explorer (GeneEx): an interactive web-app for visualizing, simulating and analyzing gene regulatory circuits

2020 ◽  
Author(s):  
Vivek Kohar ◽  
Danya Gordin ◽  
Ataur Katebi ◽  
Herbert Levine ◽  
José N Onuchic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Simulated Data ◽  
Random Parameter ◽  
Supplementary Information ◽  
Gene Expression Noise ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Web App ◽  
Parameter Ranges ◽  
Gene Regulatory Circuits

Abstract Summary GeneEx is an interactive web-app that uses an ODE-based mathematical modeling approach to simulate, visualize and analyze gene regulatory circuits (GRCs) for an explicit kinetic parameter set or for a large ensemble of random parameter sets. GeneEx offers users the freedom to modify many aspects of the simulation such as the parameter ranges, the levels of gene expression noise and the GRC network topology itself. This degree of flexibility allows users to explore a variety of hypotheses by providing insight into the number and stability of attractors for a given GRC. Moreover, users have the option to upload, and subsequently compare, experimental gene expression data to simulated data generated from the analysis of a built or uploaded custom circuit. Finally, GeneEx offers a curated database that contains circuit motifs and known biological GRCs to facilitate further inquiry into these. Overall, GeneEx enables users to investigate the effects of parameter variation, stochasticity and/or topological changes on gene expression for GRCs using a systems-biology approach. Availability and implementation GeneEx is available at https://geneex.jax.org. This web-app is released under the MIT license and is free and open to all users and there is no mandatory login requirement. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Role of noise and parametric variation in the dynamics of gene regulatory circuits

2018 ◽  
Author(s):  
Vivek Kohar ◽  
Mingyang Lu
Keyword(s):  
Gene Expression ◽  
Stochastic Analysis ◽  
Computational Cost ◽  
Basins Of Attraction ◽  
Gillespie Algorithm ◽  
Extrinsic Factors ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

AbstractStochasticity in gene expression impacts the dynamics and functions of gene regulatory circuits. Intrinsic noises, including those that are caused by low copy number of molecules and transcriptional bursting, are usually studied by stochastic analysis methods, such as Gillespie algorithm and Langevin simulation. However, the role of extrinsic factors, such as cell-to-cell variability and heterogeneity in microenvironment, is still elusive. To evaluate the effects of both intrinsic and extrinsic noises, we develop a new method, named sRACIPE, by integrating stochastic analysis with random circuit perturbation (RACIPE) method. Unlike traditional methods, RACIPE generates and analyzes an ensemble of mathematical models with random kinetic parameters. Previously, we have shown that the gene expression from random models form robust and functionally related clusters. Under the framework of this randomization-based approach, here we develop two stochastic simulation schemes, aiming to reduce the computational cost without sacrificing the convergence of statistics. One scheme uses constant noise to capture the basins of attraction, and the other one uses simulated annealing to detect the stability of states. By testing the methods on several gene regulatory circuits, we found that high noise, but not large parameter variation, merges clusters together. Our approach quantifies the robustness of a gene circuit in the presence of noise and sheds light on a new mechanism of noise induced hybrid states. We have implemented sRACIPE into a freely available R package.

scholarly journals Robustness and evolvability in transcriptional regulation

2021 ◽  
Author(s):  
José Aguilar-Rodríguez ◽  
Joshua L. Payne
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Central Position ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Living Organisms ◽  
Gene Regulatory Circuits ◽  
The Relationship

The relationship between genotype and phenotype is central to our understanding of development, evolution, and disease. This relationship is known as the genotype- phenotype map. Gene regulatory circuits occupy a central position in this map, because they control when, where, and to what extent genes are expressed, and thus drive fundamental physiological, developmental, and behavioral processes in living organisms as different as bacteria and humans. Mutations that affect these gene expression patterns are often implicated in disease, so it is important that gene regulatory circuits are robust to mutation. Such mutations can also bring forth beneficial phenotypic variation that embodies or leads to evolutionary adaptations or innovations. Here we review recent theoretical and experimental work that sheds light on the robustness and evolvability of gene regulatory circuits.

scholarly journals Integrated Gene Regulatory Circuits: Celebrating the 50th Anniversary of the Operon Model

2011 ◽  
Vol 43 (4) ◽  
pp. 505-514 ◽  
Author(s):  
Shahragim Tajbakhsh ◽  
Giacomo Cavalli ◽  
Evelyne Richet
Keyword(s):  
50Th Anniversary ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

scholarly journals Synthetic 5’ UTRs can either up- or down-regulate expression upon RBP binding

2017 ◽  
Author(s):  
Noa Katz ◽  
Roni Cohen ◽  
Oz Solomon ◽  
Beate Kaufmann ◽  
Orna Atar ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Cooperative Behavior ◽  
Transcriptional Level ◽  
Rna Molecules ◽  
Regulatory Modules ◽  
Regulatory Circuits ◽  
Rna Hairpins ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

SUMMARYThe construction of complex gene regulatory networks requires both inhibitory and up-regulatory modules. However, the vast majority of RNA-based regulatory “parts” are inhibitory. Using a synthetic biology approach combined with SHAPE-Seq, we explored the regulatory effect of RBP-RNA interactions in bacterial 5’-UTRs. By positioning a library of RNA hairpins upstream of a reporter gene and co-expressing them with the matching RBP, we observed a set of regulatory responses, including translational stimulation, translational repression, and cooperative behavior. Our combined approach revealed three distinct states in-vivo: in the absence of RBPs, the RNA molecules can be found either in a molten state that is amenable to translation, or a structured phase that inhibits translation. In the presence of RBPs, the RNA molecules are in a semi-structured phase with partial translational capacity. Our work provides new insight into RBP-based regulation and a blueprint for designing complete gene regulatory circuits at the post-transcriptional level.

scholarly journals The miRNA-gene regulatory circuits in nSARS-CoV-2 and their potential correlations with pulmonary and thrombotic disorders

2020 ◽  
Author(s):  
Pankaj Khurana ◽  
Apoorv Gupta ◽  
Ragumani Sugadev ◽  
Y K Sharma ◽  
Rajeev Varshney ◽  
...  
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Cell Cycle Control ◽  
Mirna Gene ◽  
Protein Stabilization ◽  
Common Mechanism ◽  
The Novel ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

Abstract In view of the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates, diagnostic markers etc have created a new race to curb the disease. To uncover nSARS-CoV-2-related important biological features and understanding the molecular basis of this disease, network biology and miRNA-gene regulatory motif-based approach is used. 11 antiviral human-microRNAs (miRNAs) which can potentially target SARS-CoV-2 genes were collated; their direct miRNA interactors were identified and a comprehensive nSARS-CoV-2 responsive miRNA:Transcription Factor (TF):gene coregulatory network was built. 1385 miRNA:TF:gene tripartite, Feed-Forward Loops (FFLs) were identified from the network. The network topology was mapped into the biological space and the overrepresented pathways were identified. Four regulatory circuits: hsa-mir-9-5p-EP300-PLCB4, hsa-mir-324-3p-MYC-HLA-F, hsa-mir-1827-E2F1-CTSV and hsa-mir-1277-5p-SP1-CANX are identified. These miRNA-gene regulatory circuits are found to regulate signalling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. Some novel computational evidences for understanding nSARS-CoV-2 molecular mechanisms controlled by these regulatory circuits is put forth. The novel associations of miRNAs and genes identified with this infection are open for experimental validation. Further, these regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection and pulmonary diseases and thromboembolic disorders. A detailed molecular snapshot of TGF-β signalling pathway as the common mechanism that could play an important role in controlling common pathophysiology i.e. systemic inflammation, increased pulmonary pressure, ground glass opacities, D-dimer overexpression is also put forth.

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