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Author: Fuqing Wu
Publisher:
ISBN:
Category : Gene regulatory networks
Languages : en
Pages : 0
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Book Description
Synthetic gene networks have evolved from simple proof-of-concept circuits to complex therapy-oriented networks over the past fifteen years. This advancement has greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a mechanism that cells use to achieve a discrete number of mutually exclusive states in response to environmental inputs. However, complex contextual connections of gene regulatory networks in natural settings often impede the experimental establishment of the function and dynamics of each specific gene network. In this work, diverse synthetic gene networks are rationally designed and constructed using well-characterized biological components to approach the cell fate determination and state transition dynamics in multistable systems. Results show that unimodality and bimodality and trimodality can be achieved through manipulation of the signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to communicate with each other. Moreover, a synthetic quadrastable circuit is also built and experimentally demonstrated to have four stable steady states. Experiments, guided by mathematical modeling predictions, reveal that sequential inductions generate distinct cell fates by changing the landscape in sequence and hence navigating cells to different final states. Circuit function depends on the specific protein expression levels in the circuit. We then establish a protein expression predictor taking into account adjacent transcriptional regions' features through construction of 120 synthetic gene circuits (operons) in Escherichia coli. The predictor's utility is further demonstrated in evaluating genes' relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks. These combined results illustrate applications of synthetic gene networks to understand the cell fate determination and state transition dynamics in multistable systems. A protein-expression predictor is also developed to evaluate and tune circuit dynamics.
Author: Bor-Sen Chen
Publisher: CRC Press
ISBN: 1466592699
Category : Mathematics
Languages : en
Pages : 218
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Book Description
This book develops a rational design and systematic approach to construct a gene network with desired behaviors. In order to achieve this goal, the registry of standard biological parts and experimental techniques are introduced at first. Then these biological components are characterized by a standard modeling method and collected in the component libraries, which can be efficiently reused in engineering synthetic gene networks. Based on the system theory, some design specifications are provided to engineer the synthetic gene networks to robustly track the desired trajectory by employing the component libraries.
Author: Fuqing Wu
Publisher:
ISBN:
Category : Gene regulatory networks
Languages : en
Pages : 0
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Book Description
Synthetic gene networks have evolved from simple proof-of-concept circuits to complex therapy-oriented networks over the past fifteen years. This advancement has greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a mechanism that cells use to achieve a discrete number of mutually exclusive states in response to environmental inputs. However, complex contextual connections of gene regulatory networks in natural settings often impede the experimental establishment of the function and dynamics of each specific gene network. In this work, diverse synthetic gene networks are rationally designed and constructed using well-characterized biological components to approach the cell fate determination and state transition dynamics in multistable systems. Results show that unimodality and bimodality and trimodality can be achieved through manipulation of the signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to communicate with each other. Moreover, a synthetic quadrastable circuit is also built and experimentally demonstrated to have four stable steady states. Experiments, guided by mathematical modeling predictions, reveal that sequential inductions generate distinct cell fates by changing the landscape in sequence and hence navigating cells to different final states. Circuit function depends on the specific protein expression levels in the circuit. We then establish a protein expression predictor taking into account adjacent transcriptional regions' features through construction of 120 synthetic gene circuits (operons) in Escherichia coli. The predictor's utility is further demonstrated in evaluating genes' relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks. These combined results illustrate applications of synthetic gene networks to understand the cell fate determination and state transition dynamics in multistable systems. A protein-expression predictor is also developed to evaluate and tune circuit dynamics.
Author: Wilfried Weber
Publisher: Humana Press
ISBN: 9781493962242
Category : Science
Languages : en
Pages : 408
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Book Description
This book shows how to design and build synthetic gene networks in different host backgrounds. Coverage includes concepts for devising synthetic gene networks and application of mathematical models to the predictable engineering of desired network features.
Author: Pratik Saxena
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309219396
Category : Science
Languages : en
Pages : 570
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Book Description
Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases. On March 14 and 15, 2011, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to explore the current state of the science of synthetic biology, including its dependency on systems biology; discussed the different approaches that scientists are taking to engineer, or reengineer, biological systems; and discussed how the tools and approaches of synthetic and systems biology were being applied to mitigate the risks associated with emerging infectious diseases. The Science and Applications of Synthetic and Systems Biology is organized into sections as a topic-by-topic distillation of the presentations and discussions that took place at the workshop. Its purpose is to present information from relevant experience, to delineate a range of pivotal issues and their respective challenges, and to offer differing perspectives on the topic as discussed and described by the workshop participants. This report also includes a collection of individually authored papers and commentary.
Author: Bor-Sen Chen
Publisher:
ISBN: 9781306868075
Category :
Languages : en
Pages : 216
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Book Description
This book develops a rational design and systematic approach to construct a gene network with desired behaviors. In order to achieve this goal, the registry of standard biological parts and experimental techniques are introduced at first. Then these biological components are characterized by a standard modeling method and collected in the component libraries, which can be efficiently reused in engineering synthetic gene networks. Based on the system theory, some design specifications are provided to engineer the synthetic gene networks to robustly track the desired trajectory by employing the component libraries.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 448
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Book Description
Author: Melissa Kimie Takahashi
Publisher:
ISBN:
Category :
Languages : en
Pages : 299
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Book Description
A major goal of synthetic biology is to reliably engineer microorganisms to perform a variety of functions with impact in the fields of biotechnology and medicine. Cells naturally control their behavior and process information via genetic networks - webs of interactions between cellular regulatory molecules that ultimately control when specific genes are expressed. Therefore, the route that synthetic biologists have taken to engineer microorganisms has been through constructing synthetic gene networks. Historically, these networks were built using proteins that regulate transcription, but recently RNAs have emerged as versatile molecules that can be engineered to regulate all aspects of gene expression. Aside from their versatility, RNAs offer potential advantages over protein regulators for engineering synthetic gene networks. RNAs are relatively easy to engineer due to the direct relationship between their structure and function as well as the abundance of new technologies that allow us to determine RNA secondary structures. RNA regulators are typically compact in size making networks constructed out of them easier to build. Finally, RNA networks have the potential to propagate signals faster than protein networks due to their fast degradation rates. For these reasons the focus of the work presented here has been to develop new RNA transcription regulators and to lay the groundwork for using them to build RNA synthetic gene networks. Antisense RNA transcriptional attenuators (repressors) were shown to be a key component of the synthetic biology toolbox, with their ability to serve as building blocks for both signal integration logic networks and transcriptional cascades. However, in order to build more sophisticated networks, larger libraries of orthogonal attenuators that function independently are required. To address this bottleneck we developed a strategy to create chimeric fusions between the pT181 transcriptional attenuator and other natural antisense RNA translational regulators. This strategy resulted in a library of 7 orthogonal regulators. While the strategy was successful, many of the attenuators engineered during the process did not regulate gene expression. To help understand the relationship between the structure and function of these RNA regulators we characterized their structures using in-cell SHAPE-Seq and molecular dynamics simulations. In-cell SHAPE-Seq provides nucleotide-resolution chemical reactivity spectra for RNAs that reflect their structural state within the cell. By probing functional and non-functional regulators we uncovered a design principle that brings us closer to designing chimeric attenuators in silico, thus expanding the synthetic biology toolbox even further. Next, we expand the capabilities of RNAs by engineering small transcription activating RNAs (STARs). In order to build complex RNA synthetic gene networks the ability to both activate and repress gene expression is required. However, there are no known natural small RNA (sRNA) mechanisms that activate transcription. To fill this gap, we developed two sRNA regulators to activate transcription. These STAR regulators were then used to engineer new RNA logic gates, thus expanding the RNA synthetic biology toolbox. One of the bottlenecks to developing new RNA gene networks is the slow process of testing network designs in cells. To prevent this we adapted a cell- free transcription-translation (TX-TL) system to rapidly test our RNA parts and to prototype new networks. TX-TL systems incorporate all the cellular machinery necessary for gene expression, but do so in an in vitro environment therefore bypassing the limitations that come with growing cells. We use TX-TL to prototype a new RNA network, an RNA single input module and to show that RNA networks do in fact propagate signals on the fast timescales of RNA degradation rates. Finally, we aim to expand the capabilities of RNA networks by developing an RNA genetic oscillator. Our goal is to build a dual-feedback oscillator that combines two autoregulatory network motifs - negative autoregulation and positive autoregulation using the pT181 attenuator and the best STAR regulator, respectively. We describe the progress that has been made in building these two networks as well as a path forward to engineering the RNA oscillator. Altogether the work presented here has made significant progress in our ability to engineer RNA synthetic gene networks. We anticipate that the RNA regulators and tools developed here will pave the way toward future studies of RNA structure-function principles as well as the development of new RNA networks.
Author: Filippo Menolascina
Publisher: Humana
ISBN: 9781071610343
Category : Medical
Languages : en
Pages : 353
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Book Description
This volume provides clear and direct protocols to implement automated Design-Build-Test-Learn (DBTL) into synthetic biology research. Chapters detail techniques to model and simulate biological systems, redesign biological systems, setting up of an automated biolaboratory, step-by-step guide on how to perform computer aided design, RNA sequencing, microfluidics -using bacterial cell free extracts, live mammalian cells, computational and experimental procedures, metabolic burden, computational techniques to predict such burden from models, and how DNA parts can be engineered in mammalian cells to sense, and respond to, and intracellular signals in general. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Synthetic Gene Circuits: Methods and Protocols aims to ensure successful results in the further study of this vital field.
Author: Hitoshi Iba
Publisher: John Wiley & Sons
ISBN: 1118911512
Category : Computers
Languages : en
Pages : 464
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Book Description
Introducing a handbook for gene regulatory network research using evolutionary computation, with applications for computer scientists, computational and system biologists This book is a step-by-step guideline for research in gene regulatory networks (GRN) using evolutionary computation (EC). The book is organized into four parts that deliver materials in a way equally attractive for a reader with training in computation or biology. Each of these sections, authored by well-known researchers and experienced practitioners, provides the relevant materials for the interested readers. The first part of this book contains an introductory background to the field. The second part presents the EC approaches for analysis and reconstruction of GRN from gene expression data. The third part of this book covers the contemporary advancements in the automatic construction of gene regulatory and reaction networks and gives direction and guidelines for future research. Finally, the last part of this book focuses on applications of GRNs with EC in other fields, such as design, engineering and robotics. • Provides a reference for current and future research in gene regulatory networks (GRN) using evolutionary computation (EC) • Covers sub-domains of GRN research using EC, such as expression profile analysis, reverse engineering, GRN evolution, applications • Contains useful contents for courses in gene regulatory networks, systems biology, computational biology, and synthetic biology • Delivers state-of-the-art research in genetic algorithms, genetic programming, and swarm intelligence Evolutionary Computation in Gene Regulatory Network Research is a reference for researchers and professionals in computer science, systems biology, and bioinformatics, as well as upper undergraduate, graduate, and postgraduate students. Hitoshi Iba is a Professor in the Department of Information and Communication Engineering, Graduate School of Information Science and Technology, at the University of Tokyo, Toyko, Japan. He is an Associate Editor of the IEEE Transactions on Evolutionary Computation and the journal of Genetic Programming and Evolvable Machines. Nasimul Noman is a lecturer in the School of Electrical Engineering and Computer Science at the University of Newcastle, NSW, Australia. From 2002 to 2012 he was a faculty member at the University of Dhaka, Bangladesh. Noman is an Editor of the BioMed Research International journal. His research interests include computational biology, synthetic biology, and bioinformatics.
