scholarly journals picCASO: A Cellular Automaton for Spatial Organisation

2021 ◽  
Author(s):  
Sankalpa Venkatraghavan ◽  
Sathvik Anantakrishnan ◽  
Karthik Raman
Keyword(s):  
Quorum Sensing ◽  
Cellular Automaton ◽  
Computational Models ◽  
Spatial Organization ◽  
Effective Means ◽  
Microbial Consortia ◽  
Attractive Alternative ◽  
Genetic Circuits ◽  
Natural Systems ◽  
Circuit Components

AbstractMicrobial consortia exhibit spatial patterning in several environments. However, the study of such patterning is limited by the inherent complexity of natural systems. An attractive alternative to study such systems involves the use of model synthetic microbial communities, which are convenient frameworks that allow the reuse of circuit components by eliminating cross-talk through compartmentalization of modules in genetic circuits. Computational models facilitate the understanding of how spatial organization can be harnessed as a tunable parameter in 2D cultures. We propose a Quorum Sensing-Mediated Model to engineer communication between strains in a consortium. This is implemented using a cellular automaton. We further analyze the properties of this model and compare them with those of the traditionally used Metabolite Mediated Model. Our studies indicate that modulating the rate of secretion of quorum sensing molecules is the most effective means of regulating community behavior. The models and codes are available from https://github.com/RamanLab/picCASO.

Quorum Sensing Communication: Molecularly Connecting Cells, Their Neighbors, and Even Devices

2020 ◽  
Vol 11 (1) ◽  
pp. 447-468 ◽  
Author(s):  
Sally Wang ◽  
Gregory F. Payne ◽  
William E. Bentley
Keyword(s):  
Quorum Sensing ◽  
Biological Function ◽  
Cell Communication ◽  
Microbial Consortia ◽  
Cell Behavior ◽  
Molecular Signaling ◽  
Genetic Circuits ◽  
Interkingdom Signaling ◽  
The One ◽  
Synthetic Microbial Consortia

Quorum sensing (QS) is a molecular signaling modality that mediates molecular-based cell–cell communication. Prevalent in nature, QS networks provide bacteria with a method to gather information from the environment and make decisions based on the intel. With its ability to autonomously facilitate both inter- and intraspecies gene regulation, this process can be rewired to enable autonomously actuated, but molecularly programmed, genetic control. On the one hand, novel QS-based genetic circuits endow cells with smart functions that can be used in many fields of engineering, and on the other, repurposed QS circuitry promotes communication and aids in the development of synthetic microbial consortia. Furthermore, engineered QS systems can probe and intervene in interkingdom signaling between bacteria and their hosts. Lastly, QS is demonstrated to establish conversation with abiotic materials, especially by taking advantage of biological and even electronically induced assembly processes; such QS-incorporated biohybrid devices offer innovative ways to program cell behavior and biological function.

scholarly journals Model-guided design of mammalian genetic programs

2021 ◽  
Vol 7 (8) ◽  
pp. eabe9375
Author(s):  
J. J. Muldoon ◽  
V. Kandula ◽  
M. Hong ◽  
P. S. Donahue ◽  
J. D. Boucher ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Computational Models ◽  
Biological Complexity ◽  
Genetic Circuits ◽  
Cellular Functions ◽  
High Performing ◽  
Design Objective ◽  
Complex Functions ◽  
Mammalian Genetic ◽  
Analog Processing

Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multifunctional proteins integrating both transcriptional and posttranslational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.

Assessment of Machine Learning-Based Audiovisual Quality Predictors

2021 ◽  
Vol 17 (2) ◽  
pp. 1-22
Author(s):  
Mythili K. ◽  
Manish Narwaria
Keyword(s):  
Machine Learning ◽  
Signal Processing ◽  
Quality Assessment ◽  
Computational Models ◽  
Model Development ◽  
Multimedia Communication ◽  
Current Approach ◽  
Learning Ability ◽  
Data Uncertainty ◽  
Attractive Alternative

Quality assessment of audiovisual (AV) signals is important from the perspective of system design, optimization, and management of a modern multimedia communication system. However, automatic prediction of AV quality via the use of computational models remains challenging. In this context, machine learning (ML) appears to be an attractive alternative to the traditional approaches. This is especially when such assessment needs to be made in no-reference (i.e., the original signal is unavailable) fashion. While development of ML-based quality predictors is desirable, we argue that proper assessment and validation of such predictors is also crucial before they can be deployed in practice. To this end, we raise some fundamental questions about the current approach of ML-based model development for AV quality assessment and signal processing for multimedia communication in general. We also identify specific limitations associated with the current validation strategy which have implications on analysis and comparison of ML-based quality predictors. These include a lack of consideration of: (a) data uncertainty, (b) domain knowledge, (c) explicit learning ability of the trained model, and (d) interpretability of the resultant model. Therefore, the primary goal of this article is to shed some light into mentioned factors. Our analysis and proposed recommendations are of particular importance in the light of significant interests in ML methods for multimedia signal processing (specifically in cases where human-labeled data is used), and a lack of discussion of mentioned issues in existing literature.

scholarly journals Live-cell imaging reveals the spatiotemporal organization of endogenous RNA polymerase II phosphorylation at a single gene

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linda S. Forero-Quintero ◽  
William Raymond ◽  
Tetsuya Handa ◽  
Matthew N. Saxton ◽  
Tatsuya Morisaki ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Single Molecule ◽  
Computational Models ◽  
Spatial Organization ◽  
Fluorescent Antibody ◽  
Single Gene ◽  
Single Copy ◽  
Living Cells ◽  
Live Cell

AbstractThe carboxyl-terminal domain of RNA polymerase II (RNAP2) is phosphorylated during transcription in eukaryotic cells. While residue-specific phosphorylation has been mapped with exquisite spatial resolution along the 1D genome in a population of fixed cells using immunoprecipitation-based assays, the timing, kinetics, and spatial organization of phosphorylation along a single-copy gene have not yet been measured in living cells. Here, we achieve this by combining multi-color, single-molecule microscopy with fluorescent antibody-based probes that specifically bind to different phosphorylated forms of endogenous RNAP2 in living cells. Applying this methodology to a single-copy HIV-1 reporter gene provides live-cell evidence for heterogeneity in the distribution of RNAP2 along the length of the gene as well as Serine 5 phosphorylated RNAP2 clusters that remain separated in both space and time from nascent mRNA synthesis. Computational models determine that 5 to 40 RNAP2 cluster around the promoter during a typical transcriptional burst, with most phosphorylated at Serine 5 within 6 seconds of arrival and roughly half escaping the promoter in ~1.5 minutes. Taken together, our data provide live-cell support for the notion of efficient transcription clusters that transiently form around promoters and contain high concentrations of RNAP2 phosphorylated at Serine 5.

scholarly journals Controlled spatial organization of bacterial clusters reveals cell filamentation is vital for Xylella fastidiosa biofilm formation

2021 ◽  
Author(s):  
Silambarasan Anbumani ◽  
Aldeliane M. da Silva ◽  
Eduarda R. Fischer ◽  
Mariana de Souza e Silva ◽  
Antonio A.G. von Zuben ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Spatial Organization ◽  
Xylella Fastidiosa ◽  
Cell Formation ◽  
Formation Mechanisms ◽  
Cell Morphogenesis ◽  
Cell Clusters ◽  
Filamentous Cell

The morphological plasticity of bacteria to form filamentous cells commonly represents an adaptive strategy induced by stresses. In contrast, for diverse pathogens filamentous cells have been observed during biofilm formation, with function yet to be elucidated. To identify prior hypothesized quorum sensing as trigger of such cell morphogenesis, spatially controlled cell adhesion is pivotal. Here, we demonstrate highly-selective cell adhesion of the biofilm-forming phytopathogen Xylella fastidiosa to gold-patterned SiO2 substrates with well-defined geometries and dimensions. The consequent control of both cell density and distances between cell clusters using these patterns provided evidence of quorum sensing governing filamentous cell formation. While cell morphogenesis is induced by cell cluster density, filamentous cell growth is oriented towards neighboring cell clusters and distance-dependent; large interconnected cell clusters create the early biofilm structural framework. Together, our findings and investigative platform could facilitate therapeutic developments targeting biofilm formation mechanisms of X. fastidiosa and other pathogens.

scholarly journals The Weathering Microbiome of an Outcropping Granodiorite

2020 ◽  
Vol 11 ◽  
Author(s):  
Stephanie A. Napieralski ◽  
Eric E. Roden
Keyword(s):  
Essential Elements ◽  
Cellular Growth ◽  
Metabolic Energy ◽  
Microbial Consortia ◽  
Extracellular Electron Transfer ◽  
Silicate Mineral ◽  
Near Surface ◽  
Natural Systems ◽  
Luquillo Mountains ◽  
Metabolic Energy Generation

Microorganisms have long been recognized for their capacity to catalyze the weathering of silicate minerals. While the vast majority of studies on microbially mediated silicate weathering focus on organotrophic metabolism linked to nutrient acquisition, it has been recently demonstrated that chemolithotrophic ferrous iron [Fe(II)] oxidizing bacteria (FeOB) are capable of coupling the oxidation of silicate mineral Fe(II) to metabolic energy generation and cellular growth. In natural systems, complex microbial consortia with diverse metabolic capabilities can exist and interact to influence the biogeochemical cycling of essential elements, including iron. Here we combine microbiological and metagenomic analyses to investigate the potential interactions among metabolically diverse microorganisms in the near surface weathering of an outcrop of the Rio Blanco Quartz Diorite (DIO) in the Luquillo Mountains of Puerto Rico. Laboratory based incubations utilizing ground DIO as metabolic energy source for chemolithotrophic FeOB confirmed the ability of FeOB to grow via the oxidation of silicate-bound Fe(II). Dramatically accelerated rates of Fe(II)-oxidation were associated with an enrichment in microorganisms with the genetic capacity for iron oxidizing extracellular electron transfer (EET) pathways. Microbially oxidized DIO displayed an enhanced susceptibility to the weathering activity of organotrophic microorganisms compared to unoxidized mineral suspensions. Our results suggest that chemolithotrophic and organotrophic microorganisms are likely to coexist and contribute synergistically to the overall weathering of the in situ bedrock outcrop.

scholarly journals ARCHITECTURAL-URBAN-MODELING OF THE NETWORK OF PUBLIC SPACES IN THE CENTRAL PART OF THE LARGEST CITY (ON THE EXAMPLE OF KHARKIV)

2021 ◽  
Vol 3 (163) ◽  
pp. 88-93
Author(s):  
I. Dreval ◽  
A. Zhabina
Keyword(s):  
Spatial Organization ◽  
Graphical Model ◽  
Effective Means ◽  
Public Spaces ◽  
Major City ◽  
Integrated Network ◽  
Downtown Area ◽  
Subway Stations ◽  
City Structure ◽  
The City

The paper is dedicated to the problem of creating a network of public spaces in the downtown area of a major city as an effective means of its humanization. The goal of the work is to justify and develop a graphical model of the network of public spaces in the structure of the downtown area of a major city on example of Kharkiv. Analysis of the scientific works of foreign and domestic authors has shown that the issues relating to the formation of a spatially integrated network of public spaces have not been subjected to special scientific scrutiny. The use of the law of isomorphism of structures of urban planning systems suggested that a network of public spaces could have a linear-nodal spatial organization. It is shown that open public spaces are located along the streets and should be seen as part of the city’s communication framework. The placement of a significant variety of small public service elements on the first floors of the city center neighborhood development contributes to the formation of public spaces along the streets. These pedestrian spaces providing connections to subway stations are “linear” components of the network. The presence of open, undeveloped spaces in areas close to the entrances to subway stations creates attractive conditions for the formation of new types of public spaces. On the basis of analysis of placement of 8 subway stations in the structure of the downtown area of Kharkiv there was justified the assumption that it is their areas that are considered to be “nodal” elements of the networks of public spaces. In this way, a spatially integrated network of public spaces is created and presents an effective means of humanizing the urban environment as a whole. The study of the architectural and urban construction of the network of public spaces in the city structure led to the conclusion of the effectiveness of such a measure in social, economic and aesthetic aspects.

scholarly journals Investigating the dynamics of microbial consortia in spatially structured environments

2020 ◽  
Author(s):  
Sonali Gupta ◽  
Tyler D. Ross ◽  
Marcella M. Gomez ◽  
Job L. Grant ◽  
Philip A. Romero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Organization ◽  
Expression Patterns ◽  
Interaction Network ◽  
Spatial Separation ◽  
Microbial Consortia ◽  
Ecosystem Functions ◽  
Pass Filter ◽  
Low Pass Filter ◽  
Microfluidic Platform

ABSTRACTThe spatial organization of microbial communities arises from a complex interplay of biotic and abiotic interactions and is a major determinant of ecosystem functions. We design a microfluidic platform to investigate how the spatial arrangement of microbes impacts gene expression and growth. We elucidate key biochemical parameters that dictate the mapping between spatial positioning and gene expression patterns. We show that distance can establish a low-pass filter to periodic inputs, and can enhance the fidelity of information processing. Positive and negative feedback can play disparate roles in the synchronization and robustness of a genetic oscillator distributed between two strains to spatial separation. Quantification of growth and metabolite release in an amino-acid auxotroph community demonstrates that the interaction network and stability of the community are highly sensitive to temporal perturbations and spatial arrangements. In sum, our microfluidic platform can quantify spatiotemporal parameters influencing diffusion-mediated interactions in microbial consortia.

scholarly journals Virtual Parts Repository 2: Model-driven design of genetic regulatory circuits

2021 ◽  
Author(s):  
Göksel Mısırlı ◽  
Bill Yang ◽  
Katherine James ◽  
Anil Wipat
Keyword(s):  
Design Patterns ◽  
Computational Models ◽  
Environmental Changes ◽  
Computational Design ◽  
Language Models ◽  
Design Tools ◽  
Hierarchical Systems ◽  
Genetic Circuits ◽  
Model Driven ◽  
Regulatory Circuits

Engineering genetic regulatory circuits is key to the creation of biological applications that are responsive to environmental changes. Computational models can assist in understanding especially large and complex circuits where manual analysis is infeasible, permitting a model-driven design process. However, there are still few tools that offer the ability to simulate the system under design. One of the reasons for this is the lack of accessible model repositories or libraries that cater for the modular composition of models of synthetic systems that do not yet exist in nature. Here, we present the Virtual Parts Repository 2, a resource to facilitate the model-driven design of genetic regulatory circuits, which provides reusable, modular and composable models. The repository is service-oriented and can be utilized by design tools in computational workflows. Designs provided in Synthetic Biology Open Language documents are used to derive system-scale and hierarchical Systems Biology Markup Language models. We also present a rule-based modeling abstraction based on reaction networks to facilitate scalable and modular modeling of complex and large designs. This modeling abstraction incorporates design patterns such as roadblocking, distributed deployment of genetic circuits using plasmids and cellular resource dependency. The computational resources and the modeling abstraction presented in this paper allow computational design tools to take advantage of computational simulations and ultimately help facilitate more predictable applications.

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