Synthetic Biology engineering complexity and refactoring cell capabilities

Synthetic Biology engineering complexity and refactoring cell capabilities PDF

Author: Pablo Carbonell

Publisher: Frontiers Media SA

Published: 2015-10-26

Total Pages: 125

ISBN-13: 2889196852

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One of the key features of biological systems is complexity, where the behavior of high level structures is more than the sum of the direct interactions between single components. Synthetic Biologists aim to use rational design to build new systems that do not already exist in nature and that exhibit useful biological functions with different levels of complexity. One such case is metabolic engineering, where, with the advent of genetic and protein engineering, by supplying cells with chemically synthesized non-natural amino acids and sugars as new building blocks, it is now becoming feasible to introduce novel physical and chemical functions and properties into biological entities. The rules of how complex behaviors arise, however, are not yet well understood. For instance, instead of considering cells as inert chassis in which synthetic devices could be easily operated to impart new functions, the presence of these systems may impact cell physiology with reported effects on transcription, translation, metabolic fitness and optimal resource allocation. The result of these changes in the chassis may be failure of the synthetic device, unexpected or reduced device behavior, or perhaps a more permissive environment in which the synthetic device is allowed to function. While new efforts have already been made to increase standardization and characterization of biological components in order to have well known parts as building blocks for the construction of more complex devices, also new strategies are emerging to better understand the biological dynamics underlying the phenomena we observe. For example, it has been shown that the features of single biological components [i.e. promoter strength, ribosome binding affinity, etc] change depending on the context where the sequences are allocated. Thus, new technical approaches have been adopted to preserve single components activity, as genomic insulation or the utilization of prediction algorithms able to take biological context into account. There have been noteworthy advances for synthetic biology in clinical technologies, biofuel production, and pharmaceuticals production; also, metabolic engineering combined with microbial selection/adaptation and fermentation processes allowed to make remarkable progress towards bio-products formation such as bioethanol, succinate, malate and, more interestingly, heterologous products or even non-natural metabolites. However, despite the many progresses, it is still clear that ad hoc trial and error predominates over purely bottom-up, rational design approaches in the synthetic biology community. In this scenario, modelling approaches are often used as a descriptive tool rather than for the prediction of complex behaviors. The initial confidence on a pure reductionist approach to the biological world has left space to a new and deeper investigation of the complexity of biological processes to gain new insights and broaden the categories of synthetic biology. In this Research Topic we host contributions that explore and address two areas of Synthetic Biology at the intersection between rational design and natural complexity: (1) the impact of synthetic devices on the host cell, or "chassis" and (2) the impact of context on the synthetic devices. Particular attention will be given to the application of these principles to the rewiring of cell metabolism in a bottom-up fashion to produce non-natural metabolites or chemicals that should eventually serve as a substitute for petrol-derived chemicals, and, on a long-term view, to provide economical, ecological and ethical solutions to today’s energetic and societal challenges.

A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems

A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems PDF

Author: Vishwesh V. Kulkarni

Publisher: Springer

Published: 2014-07-03

Total Pages: 298

ISBN-13: 9401790477

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The complexity of biological systems has intrigued scientists from many disciplines and has given birth to the highly influential field of systems biology wherein a wide array of mathematical techniques, such as flux balance analysis, and technology platforms, such as next generation sequencing, is used to understand, elucidate, and predict the functions of complex biological systems. More recently, the field of synthetic biology, i.e., de novo engineering of biological systems, has emerged. Scientists from various fields are focusing on how to render this engineering process more predictable, reliable, scalable, affordable, and easy. Systems and control theory is a branch of engineering and applied sciences that rigorously deals with the complexities and uncertainties of interconnected systems with the objective of characterising fundamental systemic properties such as stability, robustness, communication capacity, and other performance metrics. Systems and control theory also strives to offer concepts and methods that facilitate the design of systems with rigorous guarantees on these properties. Over the last 100 years, it has made stellar theoretical and technological contributions in diverse fields such as aerospace, telecommunication, storage, automotive, power systems, and others. Can it have, or evolve to have, a similar impact in biology? The chapters in this book demonstrate that, indeed, systems and control theoretic concepts and techniques can have a significant impact in systems and synthetic biology. Volume II contains chapters contributed by leading researchers in the field of systems and synthetic biology that concern modeling physiological processes and bottom-up constructions of scalable biological systems. The modeling problems include characterisation and synthesis of memory, understanding how homoeostasis is maintained in the face of shocks and relatively gradual perturbations, understanding the functioning and robustness of biological clocks such as those at the core of circadian rhythms, and understanding how the cell cycles can be regulated, among others. Some of the bottom-up construction problems investigated in Volume II are as follows: How should biomacromolecules, platforms, and scalable architectures be chosen and synthesised in order to build programmable de novo biological systems? What are the types of constrained optimisation problems encountered in this process and how can these be solved efficiently? As the eminent computer scientist Donald Knuth put it, "biology easily has 500 years of exciting problems to work on". This edited book presents but a small fraction of those for the benefit of (1) systems and control theorists interested in molecular and cellular biology and (2) biologists interested in rigorous modelling, analysis and control of biological systems.

Genome Refactoring

Genome Refactoring PDF

Author: Natalie Kuldell

Publisher: Springer Nature

Published: 2022-06-01

Total Pages: 66

ISBN-13: 3031025695

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The science of biology celebrates the discovery and understanding of biological systems that already exist in nature. In parallel, the engineering of biology must learn how to make use of our understanding of the natural world to design and build new useful biological systems. ""Synthetic biology"" represents one example of recent work to engineer biological systems. This emerging field aims to replace the ad hoc process of assembling biological systems by primarily developing tools to assemble reliable-but-complex living organisms from standard components that can later be reused in new combination. The focus of this book is ""genome refactoring,"" one of several approaches to manage the complexity of a biological system in which the goal is to redesign the genetic elements that encode a living form--preserving the function of that form but encoding it with a genome far easier to study and extend. This book presents genome refactoring in two ways: as an important aspect of the emerging field of synthetic biology and as a powerful teaching tool to train would be professionals in the subject. Chapters focus on the overarching goals of synthetic biology and their alignment with the motivations and achievements in genome engineering; the engineering frameworks of refactoring, including genome synthesis, standardization of biological parts, and abstraction; a detailed description of the bacteriophages that have been refactored up to this point; and the methods of refactoring and contexts for that work drawn from the bacteriophage M13. Overall, these examples offer readers the potential for synthetic biology and the areas in need of further research. If successful, synthetic biology and genome refactoring could address any number of persistent societal needs, including sustainable energy, affordable and effective medicine, and green manufacturing practices. Table of Contents: Tools for Genome Engineering and Synthetic Biology / Bacteriophage as Templates for Refactoring / Methods/Teaching Protocols for M13 Reengineering / Writing and Speaking as Biological Engineers / Summary and Future Directions / Appendix A / Appendix B / Appendix C

A Systems Theoretic Approach to Systems and Synthetic Biology I: Models and System Characterizations

A Systems Theoretic Approach to Systems and Synthetic Biology I: Models and System Characterizations PDF

Author: Vishwesh V. Kulkarni

Publisher: Springer

Published: 2014-07-03

Total Pages: 332

ISBN-13: 9401790418

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The complexity of biological systems has intrigued scientists from many disciplines and has given birth to the highly influential field of systems biology wherein a wide array of mathematical techniques, such as flux balance analysis, and technology platforms, such as next generation sequencing, is used to understand, elucidate, and predict the functions of complex biological systems. More recently, the field of synthetic biology, i.e., de novo engineering of biological systems, has emerged. Scientists from various fields are focusing on how to render this engineering process more predictable, reliable, scalable, affordable, and easy. Systems and control theory is a branch of engineering and applied sciences that rigorously deals with the complexities and uncertainties of interconnected systems with the objective of characterising fundamental systemic properties such as stability, robustness, communication capacity, and other performance metrics. Systems and control theory also strives to offer concepts and methods that facilitate the design of systems with rigorous guarantees on these properties. Over the last 100 years, it has made stellar theoretical and technological contributions in diverse fields such as aerospace, telecommunication, storage, automotive, power systems, and others. Can it have, or evolve to have, a similar impact in biology? The chapters in this book demonstrate that, indeed, systems and control theoretic concepts and techniques can have a significant impact in systems and synthetic biology. Volume I provides a panoramic view that illustrates the potential of such mathematical methods in systems and synthetic biology. Recent advances in systems and synthetic biology have clearly demonstrated the benefits of a rigorous and systematic approach rooted in the principles of systems and control theory - not only does it lead to exciting insights and discoveries but it also reduces the inordinately lengthy trial-and-error process of wet-lab experimentation, thereby facilitating significant savings in human and financial resources. In Volume I, some of the leading researchers in the field of systems and synthetic biology demonstrate how systems and control theoretic concepts and techniques can be useful, or should evolve to be useful, in order to understand how biological systems function. As the eminent computer scientist Donald Knuth put it, "biology easily has 500 years of exciting problems to work on". This edited book presents but a small fraction of those for the benefit of (1) systems and control theorists interested in molecular and cellular biology and (2) biologists interested in rigorous modelling, analysis and control of biological systems.

Synthetic Biology

Synthetic Biology PDF

Author: Manuel Porcar

Publisher: Springer

Published: 2014-09-09

Total Pages: 86

ISBN-13: 9401793824

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Synthetic Biology (SB) is a revolutionary discipline with a vast range of practical applications, but is SB research really based on engineering principles? Does it contributing to the artificial synthesis of life or does it utilise approaches sufficiently advanced to fall outside the scope of biotechnology or metabolic engineering? This volume reviews the development of SB and includes the major milestones of the discipline, the ‘top-down’ and ‘bottom-up’ approaches towards the construction of an artificial cell and the development of the “iGEM” competition. We conclude that SB is an emerging field with extraordinary technological potential, but that most research projects actually are an extension of metabolic engineering since the complexity of living organisms, their tight dependence on evolution and our limited knowledge of the interactions between the molecules, actually make life difficult to engineer.

Synthetic Biology

Synthetic Biology PDF

Author: Huimin Zhao

Publisher: Academic Press

Published: 2013-03-21

Total Pages: 352

ISBN-13: 0123978203

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Synthetic Biology provides a framework to examine key enabling components in the emerging area of synthetic biology. Chapters contributed by leaders in the field address tools and methodologies developed for engineering biological systems at many levels, including molecular, pathway, network, whole cell, and multi-cell levels. The book highlights exciting practical applications of synthetic biology such as microbial production of biofuels and drugs, artificial cells, synthetic viruses, and artificial photosynthesis. The roles of computers and computational design are discussed, as well as future prospects in the field, including cell-free synthetic biology and engineering synthetic ecosystems. Synthetic biology is the design and construction of new biological entities, such as enzymes, genetic circuits, and cells, or the redesign of existing biological systems. It builds on the advances in molecular, cell, and systems biology and seeks to transform biology in the same way that synthesis transformed chemistry and integrated circuit design transformed computing. The element that distinguishes synthetic biology from traditional molecular and cellular biology is the focus on the design and construction of core components that can be modeled, understood, and tuned to meet specific performance criteria and the assembly of these smaller parts and devices into larger integrated systems that solve specific biotechnology problems. Includes contributions from leaders in the field presents examples of ambitious synthetic biology efforts including creation of artificial cells from scratch, cell-free synthesis of chemicals, fuels, and proteins, engineering of artificial photosynthesis for biofuels production, and creation of unnatural living organisms Describes the latest state-of-the-art tools developed for low-cost synthesis of ever-increasing sizes of DNA and efficient modification of proteins, pathways, and genomes Highlights key technologies for analyzing biological systems at the genomic, proteomic, and metabolomic levels which are especially valuable in pathway, whole cell, and multi-cell applications Details mathematical modeling tools and computational tools which can dramatically increase the speed of the design process as well as reduce the cost of development

Design and Analysis of Biomolecular Circuits

Design and Analysis of Biomolecular Circuits PDF

Author: Heinz Koeppl

Publisher: Springer Science & Business Media

Published: 2011-05-21

Total Pages: 407

ISBN-13: 1441967664

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The book deals with engineering aspects of the two emerging and intertwined fields of synthetic and systems biology. Both fields hold promise to revolutionize the way molecular biology research is done, the way today’s drug discovery works and the way bio-engineering is done. Both fields stress the importance of building and characterizing small bio-molecular networks in order to synthesize incrementally and understand large complex networks inside living cells. Reminiscent of computer-aided design (CAD) of electronic circuits, abstraction is believed to be the key concept to achieve this goal. It allows hiding the overwhelming complexity of cellular processes by encapsulating network parts into abstract modules. This book provides a unique perspective on how concepts and methods from CAD of electronic circuits can be leveraged to overcome complexity barrier perceived in synthetic and systems biology.

A Systems Theoretic Approach to Systems and Synthetic Biology I: Models and System Characterizations

A Systems Theoretic Approach to Systems and Synthetic Biology I: Models and System Characterizations PDF

Author: Vishwesh Kulkarni

Publisher: Springer

Published: 2014-07-16

Total Pages: 0

ISBN-13: 9789401790406

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The complexity of biological systems has intrigued scientists from many disciplines and has given birth to the highly influential field of systems biology wherein a wide array of mathematical techniques, such as flux balance analysis, and technology platforms, such as next generation sequencing, is used to understand, elucidate, and predict the functions of complex biological systems. More recently, the field of synthetic biology, i.e., de novo engineering of biological systems, has emerged. Scientists from various fields are focusing on how to render this engineering process more predictable, reliable, scalable, affordable, and easy. Systems and control theory is a branch of engineering and applied sciences that rigorously deals with the complexities and uncertainties of interconnected systems with the objective of characterising fundamental systemic properties such as stability, robustness, communication capacity, and other performance metrics. Systems and control theory also strives to offer concepts and methods that facilitate the design of systems with rigorous guarantees on these properties. Over the last 100 years, it has made stellar theoretical and technological contributions in diverse fields such as aerospace, telecommunication, storage, automotive, power systems, and others. Can it have, or evolve to have, a similar impact in biology? The chapters in this book demonstrate that, indeed, systems and control theoretic concepts and techniques can have a significant impact in systems and synthetic biology. Volume I provides a panoramic view that illustrates the potential of such mathematical methods in systems and synthetic biology. Recent advances in systems and synthetic biology have clearly demonstrated the benefits of a rigorous and systematic approach rooted in the principles of systems and control theory - not only does it lead to exciting insights and discoveries but it also reduces the inordinately lengthy trial-and-error process of wet-lab experimentation, thereby facilitating significant savings in human and financial resources. In Volume I, some of the leading researchers in the field of systems and synthetic biology demonstrate how systems and control theoretic concepts and techniques can be useful, or should evolve to be useful, in order to understand how biological systems function. As the eminent computer scientist Donald Knuth put it, "biology easily has 500 years of exciting problems to work on". This edited book presents but a small fraction of those for the benefit of (1) systems and control theorists interested in molecular and cellular biology and (2) biologists interested in rigorous modelling, analysis and control of biological systems.

Systems and Synthetic Biology

Systems and Synthetic Biology PDF

Author: Vikram Singh

Publisher: Springer

Published: 2014-12-15

Total Pages: 383

ISBN-13: 9401795142

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This textbook has been conceptualized to provide a detailed description of the various aspects of Systems and Synthetic Biology, keeping the requirements of M.Sc. and Ph.D. students in mind. Also, it is hoped that this book will mentor young scientists who are willing to contribute to this area but do not know from where to begin. The book has been divided into two sections. The first section will deal with systems biology – in terms of the foundational understanding, highlighting issues in biological complexity, methods of analysis and various aspects of modelling. The second section deals with the engineering concepts, design strategies of the biological systems ranging from simple DNA/RNA fragments, switches and oscillators, molecular pathways to a complete synthetic cell will be described. Finally, the book will offer expert opinions in legal, safety, security and social issues to present a well-balanced information both for students and scientists.

Systems Biology and Synthetic Biology

Systems Biology and Synthetic Biology PDF

Author: Pengcheng Fu

Publisher: John Wiley & Sons

Published: 2009-08-13

Total Pages: 672

ISBN-13: 9780470437971

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The genomic revolution has opened up systematic investigations and engineering designs for various life forms. Systems biology and synthetic biology are emerging as two complementary approaches, which embody the breakthrough in biology and invite application of engineering principles. Systems Biology and Synthetic Biology emphasizes the similarity between biology and engineering at the system level, which is important for applying systems and engineering theories to biology problems. This book demonstrates to students, researchers, and industry that systems biology relies on synthetic biology technologies to study biological systems, while synthetic biology depends on knowledge obtained from systems biology approaches.