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SYNTHETIC BIOLOGY - A PRIMER
Synthetic Biology -- A Primer gives a broad overview of the emerging field of synthetic biology and the foundational concepts on which it is built. It will be of interest to final year undergraduates, postgraduates and established researchers who are interested in learning about this exciting new field. The book introduces readers to fundamental concepts in molecular biology and engineering and then explores the two major themes for synthetic biology, namely 'bottom-up' and 'top-down' engineering approaches. 'Top-down' engineering utilises a conceptual framework of engineering and systematic design to build new biological systems by integrating robustly characterised biological parts into an existing system through the use of extensive mathematical modelling. The 'bottom-up' approach involves the design and building of synthetic protocells using basic chemical and biochemical building blocks from scratch. Exemplars of cutting-edge applications designed using synthetic biology principles are presented, including the production of novel biofuels from renewable feedstocks, microbial synthesis of pharmaceuticals and fine chemicals, and the design and implementation of biosensors to detect infections and environmental waste. The book also uses the Internationally Genetically Engineered Machine (iGEM) competition to illustrate the power of synthetic biology as an innovative research and training science. Finally, the primer includes a chapter on the ethical, legal and societal issues surrounding synthetic biology, illustrating the integration of social sciences in synthetic biology research.
196 pages, Hardcover
First published June 8, 2012
23 people are currently reading
302 people want to read
About the author
Geoff Baldwin
6 books1 followerGeoff Baldwin spent 37 years in the IT Industry until his retirement in 2010 after
which he studied law with the Open University.
Geoff was inspired to write 'Flee from the Shadows' after having read extensively on the horrors perpetrated by the nazis against the Hungarian Jews when the country was occupied in 1944.
His second novel 'My Sister Forever', published in early 2017 focused on the trauma experienced by a woman living in a house haunted by it's past.
Part 1 of his third 'The Dubious Exploits of a Digital Traveller' is a light-hearted look at the experiences of growing up in the 1960's. He hopes to complete Part 2 in early 2022.
Geoff lives in the village of Liss, East Hampshire.
which he studied law with the Open University.
Geoff was inspired to write 'Flee from the Shadows' after having read extensively on the horrors perpetrated by the nazis against the Hungarian Jews when the country was occupied in 1944.
His second novel 'My Sister Forever', published in early 2017 focused on the trauma experienced by a woman living in a house haunted by it's past.
Part 1 of his third 'The Dubious Exploits of a Digital Traveller' is a light-hearted look at the experiences of growing up in the 1960's. He hopes to complete Part 2 in early 2022.
Geoff lives in the village of Liss, East Hampshire.
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Displaying 1 - 9 of 9 reviews
June 23, 2024
#nsreads 19
A 101-type barebones introduction that does the trick. Reminded me of how much I've forgotten, though it was gratifying to, after an embarrassing pause, have memories from a distant scholarly past come back to me (the 9 essential amino acids are..., the central dogma is..., viral replication includes... and so on).
It was a pleasure to learn that the stirrings I felt when I first opened Campbells and realized a great deal of biological processes were amenable to physical analysis were not in vain, and indeed form the foundation of an entire field of very active inquiry. Particularly, it's at the frontiers of rational design that the core principles of engineering are most apparent and best appreciated - and this book certainly does not disappoint.
Inasmuch as it can be a bit disappointing to realize the not-so-spectacular reality behind overhyped headlines proclaiming smart cancer-curing nanobots (really they're just cleverly designed protein assemblies or liposomes, stuff you could make in a day in the lab), there's a certain elegance to it that's reminiscent of the romance of mechanical engineering. True, proper engineering dictates that replaceable, modular parts build the robustness of a system, but you can't help but stand amazed at the beautiful design of the various mechanisms and assemblies that transduce, translate and transmit motion. A very similar feeling is quickly apparent in synthetic biology, and the bibliography of this introductory text does an excellent job of guiding readers to key works.
5/5 well earnt
A 101-type barebones introduction that does the trick. Reminded me of how much I've forgotten, though it was gratifying to, after an embarrassing pause, have memories from a distant scholarly past come back to me (the 9 essential amino acids are..., the central dogma is..., viral replication includes... and so on).
It was a pleasure to learn that the stirrings I felt when I first opened Campbells and realized a great deal of biological processes were amenable to physical analysis were not in vain, and indeed form the foundation of an entire field of very active inquiry. Particularly, it's at the frontiers of rational design that the core principles of engineering are most apparent and best appreciated - and this book certainly does not disappoint.
Inasmuch as it can be a bit disappointing to realize the not-so-spectacular reality behind overhyped headlines proclaiming smart cancer-curing nanobots (really they're just cleverly designed protein assemblies or liposomes, stuff you could make in a day in the lab), there's a certain elegance to it that's reminiscent of the romance of mechanical engineering. True, proper engineering dictates that replaceable, modular parts build the robustness of a system, but you can't help but stand amazed at the beautiful design of the various mechanisms and assemblies that transduce, translate and transmit motion. A very similar feeling is quickly apparent in synthetic biology, and the bibliography of this introductory text does an excellent job of guiding readers to key works.
5/5 well earnt
March 31, 2023
CAD block diagram. These include Clotho, GenoCAD, TinkerCell
FlyBase for Drosophila fruit fly
OpenWetWare.org, partsregistry.org
high-throughput techniques
it may be possible to limit variation by vigilant standardisation of cell strains, chemical reagents, equipment and experimental protocols. A good example of a reference element is the metre.
Abstraction allows the construction of complex devices without the full understanding of the processes at each scale (Fig. 3.5). For example, in the computer industry, a laptop is designed and assembled by people who have no expertise in how transistors are fabricated into microchips.
molecular biology is time-consuming, expensive and can be unpredictable. Computational design and simulation is cheap and rapid. By placing more of the process of the synthetic biology engineering cycle in silico there is accelerated innovation and application at lower costs.
BioBrick™ and iGEM
Using engineered cells would be more predictable than using natural cells that we don’t fully understand.
What is the minimum that we call life?
Viruses act by infecting and reprogramming cells, but cannot reproduce without them. So viruses, along with transposons and prions, are not classed as free-living, and so typically they don’t count as life, instead being something more like aberrant genetic programs.
how many parts are needed to make a cell, and what is the minimum possible cell that acts as free-living life?
Prokaryotic cells with the ‘smallest’ genome and the ‘fewest’ genes seem to be discovered every few years. It seems that the more we search through nature, the smaller the cell we can find. Two recent examples discovered are Hodgkinia cicadicola with 188 genes and a genome of 144,000 bp and Carsonella ruddii with 213 genes and a genome of 144,000 bp. Both of these microbes show just how few genes are required to encode the workings of a cell; however, both are not free-living but have entered into parasitic or symbiotic relationships with other cells — effectively being dependent on genes encoded elsewhere. Perhaps the smallest known microbe that is truly free-living is Pelagibacter ubique, which is a bacterium that lives in the sea and fresh water worldwide.
An active area of research is to determine the minimal number of genes required in a living cell or to find the minimal genome (either for all life or for a specific organism). One such project has been underway since the 1990s, led by Nobel Laureate Hamilton Smith. It focuses on taking natural cells with small genomes and reducing the number of genes in these further until only the essential genes for life remain. Smith’s project has centred on M. genitalium and its 482 genes. M. genitalium contains the necessary genes for the central dogma of life — DNA replication, transcription and translation. It also contains the genes for metabolising phospholipids, utilising vitamins and for undergoing glycolysis. But by being a parasite it has managed to remove many of the genes needed for amino acid and nucleic acid biosynthesis and it does not have the enzymes required for oxidative metabolism. It also has very few regulatory genes like transcription factors or two-component systems.
comparative approach or a reductionist approach
specialised chassis cells that do not mutate would be a useful option. Contrary to this, it would also be desirable in other circumstances to have custom cells that had little protection against mutation. Chassis cells could be engineered specifically for fast evolution, containing many recombination hotspots and lacking DNA repair mechanisms. This evolution could be programmed into designer cells to enable drug discovery to be optimised in cells by synthetic biology.
Researchers have recently engineered a membrane-encapsulated chemical ‘metabolism’ that is able to synthesise complex carbohydrates from the feedstock formaldehyde, and trigger the quorum-sensing mechanism of the bacteria Vibrio harveyi. The chemical cell was able to trigger quorum sensing and bioluminescence in bacteria, indicating that a completely artificial ‘lifelike’system was able to interact with a living system. The interaction between living and non-living systems will be an important area for synthetic biology in the future.
Synthetic biology follows a hierarchical structure, building up systems from smaller components. Systems can have fairly simple behaviour (e.g. an oscillator) or more complicated behaviour (e.g. a set of metabolic pathways to synthesise a product). This means that it is assumed that they can be exchanged without affecting the behaviour of other system components that are left untouched, which is problematic in biological systems. The chassis can be a living organism (also called in vivo implementation), or it can be abiotic, providing only the necessary biochemical components for in vitro transcription and translation.
International Genetically Engineered Machine (iGEM) competition
Constitutive promoters are useful in synthetic biology for providing a constant level of a protein of interest to a system. By varying the sequence of the DNA encoding the RNA polymerase binding site, it is possible to vary the strength of the promoter and to increase or decrease the number of mRNA copies that are made from it per second.
light offers a means of controlling expression that is noninvasive and potentially has a higher degree of spatial control. Light-gathering elements to date have mostly been photoreceptors from organisms that naturally respond to light, usually plants or cyanobacteria. Often the absorption of photons by the chromophore results in a conformational change in the protein receptor, which helps to signal to the effector that light has been received. Once the effector has received a signal from the light-gathering element, it then controls gene expression in response.
Sender and receiver devices can be combined into two different cell populations to form an oscillator that is governed by the Lotka–Volterra equations. These are the same equations which govern the behaviour of predator–prey interactions in ecosystems.
parameters appearing in the model (e.g. production and decay rates)
what is the minimal amount of information necessary in order to be able to estimate the parameters of a given model.
BioModels (http://www.ebi.ac.uk/biomodels-main/
Systems Biology Markup Language (SBML) (http://sbml.org/Main_Page) or the CellML format (http://www.cellml.org/
BioNumbers (http://bionumbers.hms.harvard.edu/
Likelihood Ratio Test (LRT), the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC)
Matlab Robust Control (http://www.mathworks.com/products/rob...
ClothoCAD (http://www.clothocad.org/
The danger of accidental release of the synthetic system into unintended areas can be minimised through the use of ‘kill’ or fail-safe switches
ethanol has a relatively low energy density and is hygroscopic (takes up water),
The healthcare industry is one of the largest markets in the world
Analytical devices capable of measuring biomolecular species in patients are invaluable in characterising normal and pathological processes and to alert clinicians to appropriate medical treatment. The most widespread and developed example is the blood glucose sensors, which are used by millions of people daily. However, these technologies are limited to the detection of one compound (glucose) and cannot be tailored to sense other biomolecules. The generation of biosensors remains very much a research project, where significant amounts of resources are required to develop unique solutions for each compound one desires to detect. Given the explosion in biomolecular data from laboratory and clinical studies, the lack of a platform for tailoring biomolecular detection is a fundamental bottleneck to the era of personalised medicine. A detection platform that could be rapidly tailored for nucleic acids or proteins would enable clinicians to take advantage of the wealth of genomic and proteomic data available.
The involvement of microbes in metal extraction (known as biomining) has a long history
One of the frontiers of synthetic biology is the design and engineering of crops able to survive drought, high salinity soil and heavy metal exposure while producing high yields of safe produce.
prizes are awarded for projects that stand out in key aspects, such as the best mathematical models, the best wiki, the best poster, the best human practices and the best new part.
cause chronic illness or be targeted to attack certain ethnic groups
constructing an Ebola virus in their garage.
‘bioterror’ and ‘bioerror’
software has run into the problem of being too functional to fit within copyright law, but also too algorithmic and nontangible to be patentable.
Current DNA sequencing is based on a method developed by Fredrick Sanger. At its heart is a PCR amplification reaction similar to what is described above, but with modified nucleotides mixed in. These nucleotides lack the necessary chemical group to enable further chain extension and thus cause early termination of the amplification.
fluorescent dye which intercalates into the DNA that is formed. This allows a measurement of DNA concentration
Deterministic model: Mathematical model in which outcomes are precisely determined through known relationships among states and events, without any room for random variation.
Genome Engineering: The rational re-writing, editing or complete novel design of whole genomes.
High-throughput techniques: Experimental methods that process hundreds or thousands of samples in parallel, rather than one at a time.
High-value added: Molecules which can be sold for much more than the cost of the starting materials.
In silico: Performed on computer or via computer simulation.
In vitro: Performed not in a living organism but in a controlled environment, such as in a test tube or Petri dish.
In vivo: Performed in live cells or living organisms.
Inverter: Another term for NOT gate
Orthogonal/orthogonality: When two or more similar systems are engineered so that they cannot interact with each other.
Parsimony or Occam’s Razor Principle: Principle which generally recommends selecting the competing hypothesis that makes the fewest new assumptions when the hypotheses are equal in other respects. The Razor is a principle that suggests we should tend towards simpler theories until we can trade some simplicity for increased explanatory power/accurateness.
Prion: A self-replicating protein.
Scale-up: The act of moving a manufacturing process from the laboratory into larger reactors.
FlyBase for Drosophila fruit fly
OpenWetWare.org, partsregistry.org
high-throughput techniques
it may be possible to limit variation by vigilant standardisation of cell strains, chemical reagents, equipment and experimental protocols. A good example of a reference element is the metre.
Abstraction allows the construction of complex devices without the full understanding of the processes at each scale (Fig. 3.5). For example, in the computer industry, a laptop is designed and assembled by people who have no expertise in how transistors are fabricated into microchips.
molecular biology is time-consuming, expensive and can be unpredictable. Computational design and simulation is cheap and rapid. By placing more of the process of the synthetic biology engineering cycle in silico there is accelerated innovation and application at lower costs.
BioBrick™ and iGEM
Using engineered cells would be more predictable than using natural cells that we don’t fully understand.
What is the minimum that we call life?
Viruses act by infecting and reprogramming cells, but cannot reproduce without them. So viruses, along with transposons and prions, are not classed as free-living, and so typically they don’t count as life, instead being something more like aberrant genetic programs.
how many parts are needed to make a cell, and what is the minimum possible cell that acts as free-living life?
Prokaryotic cells with the ‘smallest’ genome and the ‘fewest’ genes seem to be discovered every few years. It seems that the more we search through nature, the smaller the cell we can find. Two recent examples discovered are Hodgkinia cicadicola with 188 genes and a genome of 144,000 bp and Carsonella ruddii with 213 genes and a genome of 144,000 bp. Both of these microbes show just how few genes are required to encode the workings of a cell; however, both are not free-living but have entered into parasitic or symbiotic relationships with other cells — effectively being dependent on genes encoded elsewhere. Perhaps the smallest known microbe that is truly free-living is Pelagibacter ubique, which is a bacterium that lives in the sea and fresh water worldwide.
An active area of research is to determine the minimal number of genes required in a living cell or to find the minimal genome (either for all life or for a specific organism). One such project has been underway since the 1990s, led by Nobel Laureate Hamilton Smith. It focuses on taking natural cells with small genomes and reducing the number of genes in these further until only the essential genes for life remain. Smith’s project has centred on M. genitalium and its 482 genes. M. genitalium contains the necessary genes for the central dogma of life — DNA replication, transcription and translation. It also contains the genes for metabolising phospholipids, utilising vitamins and for undergoing glycolysis. But by being a parasite it has managed to remove many of the genes needed for amino acid and nucleic acid biosynthesis and it does not have the enzymes required for oxidative metabolism. It also has very few regulatory genes like transcription factors or two-component systems.
comparative approach or a reductionist approach
specialised chassis cells that do not mutate would be a useful option. Contrary to this, it would also be desirable in other circumstances to have custom cells that had little protection against mutation. Chassis cells could be engineered specifically for fast evolution, containing many recombination hotspots and lacking DNA repair mechanisms. This evolution could be programmed into designer cells to enable drug discovery to be optimised in cells by synthetic biology.
Researchers have recently engineered a membrane-encapsulated chemical ‘metabolism’ that is able to synthesise complex carbohydrates from the feedstock formaldehyde, and trigger the quorum-sensing mechanism of the bacteria Vibrio harveyi. The chemical cell was able to trigger quorum sensing and bioluminescence in bacteria, indicating that a completely artificial ‘lifelike’system was able to interact with a living system. The interaction between living and non-living systems will be an important area for synthetic biology in the future.
Synthetic biology follows a hierarchical structure, building up systems from smaller components. Systems can have fairly simple behaviour (e.g. an oscillator) or more complicated behaviour (e.g. a set of metabolic pathways to synthesise a product). This means that it is assumed that they can be exchanged without affecting the behaviour of other system components that are left untouched, which is problematic in biological systems. The chassis can be a living organism (also called in vivo implementation), or it can be abiotic, providing only the necessary biochemical components for in vitro transcription and translation.
International Genetically Engineered Machine (iGEM) competition
Constitutive promoters are useful in synthetic biology for providing a constant level of a protein of interest to a system. By varying the sequence of the DNA encoding the RNA polymerase binding site, it is possible to vary the strength of the promoter and to increase or decrease the number of mRNA copies that are made from it per second.
light offers a means of controlling expression that is noninvasive and potentially has a higher degree of spatial control. Light-gathering elements to date have mostly been photoreceptors from organisms that naturally respond to light, usually plants or cyanobacteria. Often the absorption of photons by the chromophore results in a conformational change in the protein receptor, which helps to signal to the effector that light has been received. Once the effector has received a signal from the light-gathering element, it then controls gene expression in response.
Sender and receiver devices can be combined into two different cell populations to form an oscillator that is governed by the Lotka–Volterra equations. These are the same equations which govern the behaviour of predator–prey interactions in ecosystems.
parameters appearing in the model (e.g. production and decay rates)
what is the minimal amount of information necessary in order to be able to estimate the parameters of a given model.
BioModels (http://www.ebi.ac.uk/biomodels-main/
Systems Biology Markup Language (SBML) (http://sbml.org/Main_Page) or the CellML format (http://www.cellml.org/
BioNumbers (http://bionumbers.hms.harvard.edu/
Likelihood Ratio Test (LRT), the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC)
Matlab Robust Control (http://www.mathworks.com/products/rob...
ClothoCAD (http://www.clothocad.org/
The danger of accidental release of the synthetic system into unintended areas can be minimised through the use of ‘kill’ or fail-safe switches
ethanol has a relatively low energy density and is hygroscopic (takes up water),
The healthcare industry is one of the largest markets in the world
Analytical devices capable of measuring biomolecular species in patients are invaluable in characterising normal and pathological processes and to alert clinicians to appropriate medical treatment. The most widespread and developed example is the blood glucose sensors, which are used by millions of people daily. However, these technologies are limited to the detection of one compound (glucose) and cannot be tailored to sense other biomolecules. The generation of biosensors remains very much a research project, where significant amounts of resources are required to develop unique solutions for each compound one desires to detect. Given the explosion in biomolecular data from laboratory and clinical studies, the lack of a platform for tailoring biomolecular detection is a fundamental bottleneck to the era of personalised medicine. A detection platform that could be rapidly tailored for nucleic acids or proteins would enable clinicians to take advantage of the wealth of genomic and proteomic data available.
The involvement of microbes in metal extraction (known as biomining) has a long history
One of the frontiers of synthetic biology is the design and engineering of crops able to survive drought, high salinity soil and heavy metal exposure while producing high yields of safe produce.
prizes are awarded for projects that stand out in key aspects, such as the best mathematical models, the best wiki, the best poster, the best human practices and the best new part.
cause chronic illness or be targeted to attack certain ethnic groups
constructing an Ebola virus in their garage.
‘bioterror’ and ‘bioerror’
software has run into the problem of being too functional to fit within copyright law, but also too algorithmic and nontangible to be patentable.
Current DNA sequencing is based on a method developed by Fredrick Sanger. At its heart is a PCR amplification reaction similar to what is described above, but with modified nucleotides mixed in. These nucleotides lack the necessary chemical group to enable further chain extension and thus cause early termination of the amplification.
fluorescent dye which intercalates into the DNA that is formed. This allows a measurement of DNA concentration
Deterministic model: Mathematical model in which outcomes are precisely determined through known relationships among states and events, without any room for random variation.
Genome Engineering: The rational re-writing, editing or complete novel design of whole genomes.
High-throughput techniques: Experimental methods that process hundreds or thousands of samples in parallel, rather than one at a time.
High-value added: Molecules which can be sold for much more than the cost of the starting materials.
In silico: Performed on computer or via computer simulation.
In vitro: Performed not in a living organism but in a controlled environment, such as in a test tube or Petri dish.
In vivo: Performed in live cells or living organisms.
Inverter: Another term for NOT gate
Orthogonal/orthogonality: When two or more similar systems are engineered so that they cannot interact with each other.
Parsimony or Occam’s Razor Principle: Principle which generally recommends selecting the competing hypothesis that makes the fewest new assumptions when the hypotheses are equal in other respects. The Razor is a principle that suggests we should tend towards simpler theories until we can trade some simplicity for increased explanatory power/accurateness.
Prion: A self-replicating protein.
Scale-up: The act of moving a manufacturing process from the laboratory into larger reactors.
December 19, 2022
A great introductory text on Synthetic Biology. In 140 pages, the text gives a good description of the fundamental principles of the field (use of abstraction, standardized biological parts that are well described) as well as the developments of the field up to the book's publication in 2012.
July 11, 2017
Get introduction to this fascination new field!
June 1, 2020
Quite dated but good.
March 14, 2015
A pretty good survey of the state of current (as of 2012) synthetic biology, with particular attention to the application of systems engineering concepts to the development of biological applications.
There's a nice chapter on general engineering principles, such as the Laplace Domain and block diagrams, demonstrating how they can be applied to genetic systems; likewise signal and control theory, the Nyquist-Shannon sampling critereon of information theory, and so on. The book also offers a nice overview of technologies such as PCR, BioCAD, and efforts such as the development of genetic registries for parts/devices/systems approaches to designing application-oriented life.
It's dense, and somewhat technical, but easily accessible to anyone with an undergraduate background in biochemistry or molecular biology; I read it to "update" my knowledge of what we *used* to call genetic engineering, since I'm from the era of recombinant DNA. It has an excellent, comprehensive bibliography as well, for those seeking to delve further.
There's a nice chapter on general engineering principles, such as the Laplace Domain and block diagrams, demonstrating how they can be applied to genetic systems; likewise signal and control theory, the Nyquist-Shannon sampling critereon of information theory, and so on. The book also offers a nice overview of technologies such as PCR, BioCAD, and efforts such as the development of genetic registries for parts/devices/systems approaches to designing application-oriented life.
It's dense, and somewhat technical, but easily accessible to anyone with an undergraduate background in biochemistry or molecular biology; I read it to "update" my knowledge of what we *used* to call genetic engineering, since I'm from the era of recombinant DNA. It has an excellent, comprehensive bibliography as well, for those seeking to delve further.
May 13, 2023
BAgus lah untuk yang mau tau basic Synbio secara informasi (bukan secara teknis ya). Saya bisa enjoy baca buku ini dengan bermodalkan penmgetahuan kimia dan biology SMA. Tapi ada juga bebberapa bab yang perlu wawasan tambahan yang mungkin harus dicari di sumber lain (YT, jurnal dkk). Ya intinya kalau mau info synbio yang keren ya memang dari jurnal/artikel sihhh, dan juga masih dikit banget buku tentang synbio (yg teknis).
b uku ini ga direkom untuk yang mau tau mendalam tentang synbio, terutama tentang aplikasi synbio di bidang yang lebih spesifik (mungkin karena synbio juga masih baru jdnya jarang ada buku yang lebih sbahas bidang spesifik). tapi So far bole la utk basic aja....
b uku ini ga direkom untuk yang mau tau mendalam tentang synbio, terutama tentang aplikasi synbio di bidang yang lebih spesifik (mungkin karena synbio juga masih baru jdnya jarang ada buku yang lebih sbahas bidang spesifik). tapi So far bole la utk basic aja....
June 14, 2016
Enjoyable overview. Mostly geared towards a general audience, with some detailed science thrown in the mix.
May 17, 2016
Chapters on the actual synthetic biology techniques are great, but lots of systems biology stuff is portly explained for people without mathematical/ engineering background.
Displaying 1 - 9 of 9 reviews