scholarly journals Engineered phenotype patterns in microbial populations

2019 ◽  
Author(s):  
Philip Bittihn ◽  
Andriy Didovyk ◽  
Lev S. Tsimring ◽  
Jeff Hasty
Keyword(s):  
Gene Expression ◽  
Synthetic Biology ◽  
Expression Patterns ◽  
Local Environment ◽  
Heterogeneous Environments ◽  
Gene Circuits ◽  
Sensor Module ◽  
Dividing Cells ◽  
Actuator Module ◽  
And Control

AbstractRapid advances in cellular engineering1,2have positioned synthetic biology to address therapeutic3,4and industrial5problems, but a significant obstacle is the myriad of unanticipated cellular responses in heterogeneous environments such as the gut6,7, solid tumors8,9, bioreactors10or soil11. Complex interactions between the environment and cells often arise through non-uniform nutrient availability, which can generatebidirectionalcoupling as cells both adjust to and modify their local environment through different growth phenotypes across a colony.12,13While spatial sensing14and gene expression patterns15–17have been explored under homogeneous conditions, the mutual interaction between gene circuits, growth phenotype, and the environment remains a challenge for synthetic biology. Here, we design gene circuits which sense and control spatiotemporal phenotype patterns in a model system of heterogeneous microcolonies containing both growing and dormant bacteria. We implement pattern control by coupling different downstream modules to a tunable sensor module that leveragesE. coli⁉sstress response and is activated upon growth arrest. One is an actuator module that slows growth and thereby creates an environmental negative feedback via nutrient diffusion. We build a computational model of this system to understand the interplay between gene regulation, population dynamics, and chemical transport, which predicts oscillations in both growth and gene expression. Experimentally, this circuit indeed generates robust cycling between growth and dormancy in the interior of the colony. We also use the stress sensor to drive an inducible gating module that enables selective gene expression in non-dividing cells. The ‘stress-gated lysis circuit’ derived from this module radically alters the growth pattern through elimination of the dormant phenotype upon a chemical cue. Our results establish a strategy to leverage and control the presence of distinct microbial growth phenotypes for synthetic biology applications in complex environments.

scholarly journals GLO-Roots: an imaging platform enabling multidimensional characterization of soil-grown root systems

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Rubén Rellán-Álvarez ◽  
Guillaume Lobet ◽  
Heike Lindner ◽  
Pierre-Luc Pradier ◽  
Jose Sebastian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Imaging System ◽  
Expression Patterns ◽  
Local Environment ◽  
Root Systems ◽  
Root System Architecture ◽  
Spatial Integration ◽  
Adaptive Responses ◽  
Physiological Relevance ◽  
Great Utility

Root systems develop different root types that individually sense cues from their local environment and integrate this information with systemic signals. This complex multi-dimensional amalgam of inputs enables continuous adjustment of root growth rates, direction, and metabolic activity that define a dynamic physical network. Current methods for analyzing root biology balance physiological relevance with imaging capability. To bridge this divide, we developed an integrated-imaging system called Growth and Luminescence Observatory for Roots (GLO-Roots) that uses luminescence-based reporters to enable studies of root architecture and gene expression patterns in soil-grown, light-shielded roots. We have developed image analysis algorithms that allow the spatial integration of soil properties, gene expression, and root system architecture traits. We propose GLO-Roots as a system that has great utility in presenting environmental stimuli to roots in ways that evoke natural adaptive responses and in providing tools for studying the multi-dimensional nature of such processes.

Conserved and muscle-group-specific gene expression patterns shape postnatal development of the novel extraocular muscle phenotype

2004 ◽  
Vol 18 (2) ◽  
pp. 184-195 ◽  
Author(s):  
Georgiana Cheng ◽  
Anita P. Merriam ◽  
Bendi Gong ◽  
Patrick Leahy ◽  
Sangeeta Khanna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
System Development ◽  
Expression Patterns ◽  
Neuromuscular Diseases ◽  
Local Environment ◽  
Oculomotor System ◽  
Muscle Group ◽  
Specific Gene ◽  
Extrinsic Factors

Current models in skeletal muscle biology do not fully account for the breadth, causes, and consequences of phenotypic variation among skeletal muscle groups. The muscle allotype concept arose to explain frank differences between limb, masticatory, and extraocular (EOM) muscles, but there is little understanding of the developmental regulation of the skeletal muscle phenotypic range. Here, we used morphological and DNA microarray analyses to generate a comprehensive temporal profile for rat EOM development. Based upon coordinate regulation of morphologic/gene expression traits with key events in visual, vestibular, and oculomotor system development, we propose a model that the EOM phenotype is a consequence of extrinsic factors that are unique to its local environment and sensory-motor control system, acting upon a novel myoblast lineage. We identified a broad spectrum of differences between the postnatal transcriptional patterns of EOM and limb muscle allotypes, including numerous transcripts not traditionally associated with muscle fiber/group differences. Several transcription factors were differentially regulated and may be responsible for signaling muscle allotype specificity. Significant differences in cellular energetic mechanisms defined the EOM and limb allotypes. The allotypes were divergent in many other functional transcript classes that remain to be further explored. Taken together, we suggest that the EOM allotype is the consequence of tissue-specific mechanisms that direct expression of a limited number of EOM-specific transcripts and broader, incremental differences in transcripts that are conserved by the two allotypes. This represents an important first step in dissecting allotype-specific regulatory mechanisms that may, in turn, explain differential muscle group sensitivity to a variety of metabolic and neuromuscular diseases.

scholarly journals Synthetic biology: paving the way with novel drug delivery

2019 ◽  
Vol 41 (3) ◽  
pp. 24-27 ◽  
Author(s):  
Lucas M. Bush ◽  
Chelsea Gibbs ◽  
Tara L. Deans
Keyword(s):  
Gene Expression ◽  
Drug Delivery ◽  
Synthetic Biology ◽  
Rational Design ◽  
Control Cell ◽  
Regulation Of Gene Expression ◽  
Modern Technology ◽  
Gene Circuits ◽  
Basic Concepts ◽  
Novel Drug

Synthetic biology is a multidisciplinary field that focuses on the rational design and construction of novel genetic tools for the purpose of engineering cells to behave in controllable and predictable ways. The promise of this modern technology relies on our understanding of basic genetics and gene expression to engineer cells with unique functions. This is accomplished by designing biological parts and assembling them into higher-order gene circuits that control cell operations through tight regulation of gene expression, effectively reprogramming and rewiring the cells. In this article, we review the basic concepts of gene expression, discuss the framework of how synthetic biologists reprogram cells and outline how cells can be engineered to function as new vehicles for delivering therapeutic proteins.

scholarly journals Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks

2019 ◽  
Author(s):  
Katherine Exelby ◽  
Edgar Herrera-Delgado ◽  
Lorena Garcia Perez ◽  
Ruben Perez-Carrasco ◽  
Andreas Sagner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Cell Fates ◽  
Gene Circuits ◽  
Stochastic Fluctuations ◽  
Network Properties ◽  
Gene Regulatory

AbstractDuring development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.

Actin and tubulin in Tetrahymena

1985 ◽  
Vol 63 (6) ◽  
pp. 389-396 ◽  
Author(s):  
E. Jane Mitchell ◽  
Selma Zimmerman ◽  
Arthur M. Zimmerman
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Tetrahymena Pyriformis ◽  
Model System ◽  
Cytoskeletal Proteins ◽  
Actin Gene ◽  
Ciliated Protozoan ◽  
Dividing Cells ◽  
And Control

Tubulin and actin are cytoskeletal proteins known to play a major role in dividing cells. Tetrahymena pyriformis, a ciliated protozoan, was used as a model system for investigating tubulin synthesis during cilia regeneration and during the cell cycle. Until recently the identification of actin in Tetrahymena has been controversial. In this report evidence for the presence of actin in Tetrahymena is reviewed and control of actin gene expression during the cell cycle is discussed.

scholarly journals A multiscale model of complex endothelial cell dynamics in early angiogenesis

2021 ◽  
Vol 17 (1) ◽  
pp. e1008055
Author(s):  
Daria Stepanova ◽  
Helen M. Byrne ◽  
Philip K. Maini ◽  
Tomás Alarcón
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Experimental Studies ◽  
Notch Pathway ◽  
Local Environment ◽  
Multiscale Model ◽  
Vascular Network ◽  
Border Effect ◽  
Potential Biomarker ◽  
The Impact

We introduce a hybrid two-dimensional multiscale model of angiogenesis, the process by which endothelial cells (ECs) migrate from a pre-existing vascular bed in response to local environmental cues and cell-cell interactions, to create a new vascular network. Recent experimental studies have highlighted a central role of cell rearrangements in the formation of angiogenic networks. Our model accounts for this phenomenon via the heterogeneous response of ECs to their microenvironment. These cell rearrangements, in turn, dynamically remodel the local environment. The model reproduces characteristic features of angiogenic sprouting that include branching, chemotactic sensitivity, the brush border effect, and cell mixing. These properties, rather than being hardwired into the model, emerge naturally from the gene expression patterns of individual cells. After calibrating and validating our model against experimental data, we use it to predict how the structure of the vascular network changes as the baseline gene expression levels of the VEGF-Delta-Notch pathway, and the composition of the extracellular environment, vary. In order to investigate the impact of cell rearrangements on the vascular network structure, we introduce the mixing measure, a scalar metric that quantifies cell mixing as the vascular network grows. We calculate the mixing measure for the simulated vascular networks generated by ECs of different lineages (wild type cells and mutant cells with impaired expression of a specific receptor). Our results show that the time evolution of the mixing measure is directly correlated to the generic features of the vascular branching pattern, thus, supporting the hypothesis that cell rearrangements play an essential role in sprouting angiogenesis. Furthermore, we predict that lower cell rearrangement leads to an imbalance between branching and sprout elongation. Since the computation of this statistic requires only individual cell trajectories, it can be computed for networks generated in biological experiments, making it a potential biomarker for pathological angiogenesis.

scholarly journals Gene Expression Patterns in Calorically Restricted Mice: Partial Overlap with Long-Lived Mutant Mice

2002 ◽  
Vol 16 (11) ◽  
pp. 2657-2666 ◽  
Author(s):  
Richard A. Miller ◽  
Yayi Chang ◽  
Andrzej T. Galecki ◽  
Khalid Al-Regaiey ◽  
John J. Kopchick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Selection Criterion ◽  
Life Extension ◽  
Functional Classes ◽  
Snell Dwarf ◽  
Liver Gene ◽  
Partial Overlap ◽  
And Control ◽  
Dwarf Mice

Abstract To gain insight into the pathways by which caloric restriction (CR) slows aging, gene expression levels were assessed for each of 2352 genes in the livers of 9-month-old CR and control mice. A total of 352 genes were found to be significantly increased or decreased by CR. The distribution of affected genes among functional classes was similar to the distribution of genes within the test set. Surprisingly, a disruption or knockout of the gene for the GH receptor (GHR-KO), which also produces life extension, had a much smaller effect on gene expression, with no more than 10 genes meeting the selection criterion. There was, however, an interaction between the GHR-KO mutation and the CR diet: the effects of CR on gene expression were significantly lower in GHR-KO mice than in control mice. Of the 352 genes altered significantly by CR, 29 had shown a significant and parallel alteration in expression in a previous study of liver gene expression that compared mice of the long-lived Snell dwarf stock (dw/dw) to controls. These 29 genes, altered both by CR and in dwarf mice, provide a list of biochemical features common to both models of delayed aging, and thus merit confirmation and more detailed study.

scholarly journals Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev197566
Author(s):  
Katherine Exelby ◽  
Edgar Herrera-Delgado ◽  
Lorena Garcia Perez ◽  
Ruben Perez-Carrasco ◽  
Andreas Sagner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Cell Fates ◽  
Gene Circuits ◽  
Stochastic Fluctuations ◽  
Network Properties ◽  
Gene Regulatory

ABSTRACTDuring development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.

scholarly journals Transcriptome profiling of ‘Kyoho’ grape at different stages of berry development following 5-azaC treatment

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Da-Long Guo ◽  
Qiong Li ◽  
Xiao-Ru Ji ◽  
Zhen-Guang Wang ◽  
Yi-He Yu
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Transcriptome Profiling ◽  
Grape Berry ◽  
Control Groups ◽  
Hub Genes ◽  
Histone Lysine ◽  
Gene Correlation ◽  
And Control

Abstract Background 5-Azacytidine (5-azaC) promotes the development of ‘Kyoho’ grape berry but the associated changes in gene expression have not been reported. In this study, we performed transcriptome analysis of grape berry at five developmental stages after 5-azaC treatment to elucidate the gene expression networks controlling berry ripening. Results The expression patterns of most genes across the time series were similar between the 5-azaC treatment and control groups. The number of differentially expressed genes (DEGs) at a given developmental stage ranged from 9 (A3_C3) to 690 (A5_C5). The results indicated that 5-azaC treatment had not very great influences on the expressions of most genes. Functional annotation of the DEGs revealed that they were mainly related to fruit softening, photosynthesis, protein phosphorylation, and heat stress. Eight modules showed high correlation with specific developmental stages and hub genes such as PEROXIDASE 4, CAFFEIC ACID 3-O-METHYLTRANSFERASE 1, and HISTONE-LYSINE N-METHYLTRANSFERASE EZA1 were identified by weighted gene correlation network analysis. Conclusions 5-AzaC treatment alters the transcriptional profile of grape berry at different stages of development, which may involve changes in DNA methylation.

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