There are certain aspects my CytoComp project where I see solutions in Bitcoin 2.0 / BlockChain technology.
DNA sequencing and synthesis plays a central role in synthetic biology.
One problem is the secure sharing and analysis of DNA data. It is possible to track the identity of a person from shared DNA sequences without an identifier http://www.sciencemag.org/content/339/6117/321.abstract. As genomics play an increasingly important role in modern medicine, this is a major problem. DNA data are highly sensitive and sequencing information has a huge potential for misuse. I think it is possible to use BlockChain technology to securely share these kind of data P2P.
Moreover, DNA data are huge files and will in the future need increasing computing power to be rapidly analyzed. The design of DNA sequences might also sometimes need larger computing power. I see the option to chop up these large DNA data files and analyze these parts by utilizing secure multiparty computing. I think platforms like Ethereum are well suited to build a secure DNA analysis app.
A token, specific coin would be great to use in this system in order to pay for expenses.
Thus as a starting point, please share your thoughts and suggest a name.
BTW if anybody is interested to join such a project - let me know.
by Daven Sanassy , Pawel Widera , and Natalio Krasnogor
"Stochastic simulation algorithms (SSAs) are used to trace realistic trajectories of biochemical systems at low species concentrations. As the complexity of modelled bio-systems increases, it is important to select the best performing SSA. Numerous improvements to SSAs have been introduced but they each only tend to apply to a certain class of models. This makes it difficult for a systems or synthetic biologist to decide which algorithm to employ when confronted with a new model that requires simulation. In this paper we demonstrate that it is possible to determine which algorithm is best suited to simulate a particular model, and that this can be predicted a priori to algorithm execution. We present a web based tool ssapredict that allows scientists to upload a biochemical model and obtain a prediction of the best performing SSA. Furthermore, ssapredict gives the user the option to download our high performance simulator ngss preconfigured to perform the simulation of the queried biochemical model with the predicted fastest algorithm as the simulation engine. It is free software and its source code is distributed under the terms of GNU Affero General Public License."
eLife - Open access to the most promising advances in science
Socrates Logos's insight:
by Owen W Ryan, Jeffrey M Skerker, Matthew J Maurer, Xin Li, Jordan C Tsai, Snigdha Poddar, Michael E Lee, Will DeLoache, John E Dueber, Adam P Arkin, Jamie H D Cate
"The directed evolution of biomolecules to improve or change their activity is central to many engineering and synthetic biology efforts. However, selecting improved variants from gene libraries in living cells requires plasmid expression systems that suffer from variable copy number effects, or the use of complex marker-dependent chromosomal integration strategies. We developed quantitative gene assembly and DNA library insertion into the Saccharomyces cerevisiae genome by optimizing an efficient single-step and marker-free genome editing system using CRISPR-Cas9. With this Multiplex CRISPR (CRISPRm) system, we selected an improved cellobiose utilization pathway in diploid yeast in a single round of mutagenesis and selection, which increased cellobiose fermentation rates by over ten-fold. Mutations recovered in the best cellodextrin transporters reveal synergy between substrate binding and transporter dynamics, and demonstrate the power of CRISPRm to accelerate selection experiments and discoveries of the molecular determinants that enhance biomolecule function."
"Cells proliferate by division into similar daughter cells, a process that lies at the heart of cell biology. Extensive research on cell division has led to the identification of the many components and control elements of the molecular machinery underlying cellular division. Here we provide a brief review of prokaryotic and eukaryotic cell division and emphasize how new approaches such as systems and synthetic biology can provide valuable new insight."
"With the recent dawn of synthetic biology, the old idea of man-made artificial life has gained renewed interest. In the context of a bottom-up approach, this entails the de novo construction of synthetic cells that can autonomously sustain themselves and proliferate. Reproduction of a synthetic cell involves the synthesis of its inner content, replication of its information module, and growth and division of its shell. Theoretical and experimental analysis of natural cells shows that, whereas the core synthesis machinery of the information module is highly conserved, a wide range of solutions have been realized in order to accomplish division. It is therefore to be expected that there are multiple ways to engineer division of synthetic cells. Here we survey the field and review potential routes that can be explored to accomplish the division of bottom-up designed synthetic cells. We cover a range of complexities from simple abiotic mechanisms involving splitting of lipid-membrane-encapsulated vesicles due to physical or chemical principles, to potential division mechanisms of synthetic cells that are based on prokaryotic division machineries."
" There is a growing demand for enzymes with improved catalytic performance or tolerance to process-specific parameters, and biotechnology plays a crucial role in the development of biocatalysts for use in industry, agriculture, medicine and energy generation. Metagenomics takes advantage of the wealth of genetic and biochemical diversity present in the genomes of microorganisms found in environmental samples, and provides a set of new technologies directed towards screening for new catalytic activities from environmental samples with potential biotechnology applications. However, biased and low level of expression of heterologous proteins in Escherichia coli together with the use of non-optimal cloning vectors for the construction of metagenomic libraries generally results in an extremely low success rate for enzyme identification. The bottleneck arising from inefficient screening of enzymatic activities has been addressed from several perspectives; however, the limitations related to biased expression in heterologous hosts cannot be overcome by using a single approach, but rather requires the synergetic implementation of multiple methodologies. Here, we review some of the principal constraints regarding the discovery of new enzymes in metagenomic libraries and discuss how these might be resolved by using synthetic biology methods."
by Benjamin Reeve, imageThomas Hargest, imageCharlie Gilbert and Tom Ellis
"In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5'-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed." http://bit.ly/1pDs1vm
by Nunes SF, Hamers C, Ratinier M, Shaw A, Brunet S, Hudelet P, Palmarini M
"Bluetongue is one of the major infectious diseases of ruminants and is caused by Bluetongue virus (BTV), an arbovirus existing in nature in at least 26 distinct serotypes. Here, we describe the development of a vaccine platform for BTV. The advent of synthetic biology approaches and the development of reverse genetics systems, has allowed the rapid and reliable design and production of pathogen genomes which can be subsequently manipulated for vaccine production. We describe BTV vaccines based on "synthetic" viruses in which the outer core proteins of different BTV serotypes are incorporated into a common tissue-culture adapted backbone. As a means of validation for this approach, we selected two BTV-8 synthetic reassortants and demonstrated their ability to protect sheep against virulent BTV-8 challenge. In addition, to further highlight the possibilities of genome manipulation for vaccine production, we also designed and rescued a synthetic BTV chimera containing a VP2 protein including regions derived from both BTV-1 and BTV-8. Interestingly, while the parental viruses were neutralized only by homologous antisera, the chimeric proteins could be neutralized by both BTV-1 and BTV-8 antisera. These data suggest that neutralizing epitopes are present in different areas of the BTV VP2 and likely "bivalent" strains eliciting neutralizing antibodies for multiple strains can be obtained."
"There is a growing demand for enzymes with improved catalytic performance or tolerance to process-specific parameters, and biotechnology plays a crucial role in the development of biocatalysts for use in industry, agriculture, medicine and energy generation. Metagenomics takes advantage of the wealth of genetic and biochemical diversity present in the genomes of microorganisms found in environmental samples, and provides a set of new technologies directed towards screening for new catalytic activities from environmental samples with potential biotechnology applications. However, biased and low level of expression of heterologous proteins in Escherichia coli together with the use of non-optimal cloning vectors for the construction of metagenomic libraries generally results in an extremely low success rate for enzyme identification. The bottleneck arising from inefficient screening of enzymatic activities has been addressed from several perspectives; however, the limitations related to biased expression in heterologous hosts cannot be overcome by using a single approach, but rather requires the synergetic implementation of multiple methodologies. Here, we review some of the principal constraints regarding the discovery of new enzymes in metagenomic libraries and discuss how these might be resolved by using synthetic biology methods."
"The construction of an irreducible minimal cell having all essential attributes of a living system is one of the biggest challenges facing synthetic biology. One ubiquitous task accomplished by any living systems is the division of the cell envelope. Hence, the assembly of an elementary, albeit sufficient, molecular machinery that supports compartment division, is a crucial step towards the realization of self-reproducing artificial cells. Looking backward to the molecular nature of possible ancestral, supposedly more rudimentary, cell division systems may help to identify a minimal divisome. In light of a possible evolutionary pathway of division mechanisms from simple lipid vesicles toward modern life, we define two approaches for recapitulating division in primitive cells: the membrane deforming protein route and the lipid biosynthesis route. Having identified possible proteins and working mechanisms participating in membrane shape alteration, we then discuss how they could be integrated into the construction framework of a programmable minimal cell relying on gene expression inside liposomes. The protein synthesis using recombinant elements (PURE) system, a reconstituted minimal gene expression system, is conceivably the most versatile synthesis platform. As a first step towards the de novo synthesis of a divisome, we showed that the N-BAR domain protein produced from its gene could assemble onto the outer surface of liposomes and sculpt the membrane into tubular structures. We finally discuss the remaining challenges for building up a self-reproducing minimal cell, in particular the coupling of the division machinery with volume expansion and genome replication."
"Synthetic biology uses our understanding of biological systems to develop innovative solutions for challenges in fields as diverse as genetic control and logic devices, bioremediation, materials production or diagnostics and therapy in medicine by designing new biological components. RNA-based elements are key components of these engineered systems. Their structural and functional diversity is ideal for generating regulatory riboswitches that react with many different types of output to molecular and environmental signals. Recent advances have added new sensor and output domains to the existing toolbox, and demonstrated the portability of riboswitches to many different organisms. Improvements in riboswitch design and screens for selecting in vivo active switches provide the means to isolate riboswitches with regulatory properties more like their natural counterparts."
"IN THE SUMMER of 2009, a team of Cambridge University undergraduates built seven strains of the bacterium Escherichia coli, one in each color of the rainbow. Red and orange carotenoid pigments were produced by inserting genes from plant pathogen Pantoea ananatis; a cluster of genes from Chromobacterium violaceum were likewise modified to yield green and purple. The students’ technicolor creations, dubbed “E. chromi” in reference to the organisms’ scientific name, won the Cambridge team the grand prize at that year’s International Genetically Engineered Machines (iGEM) competition, in which high-school and college students engineer biology.
The students’ goals were not merely chromatic. Instead, they were building parts for biological machines. They engineered the genes into standardized forms called BioBricks: pieces of DNA that, like genetic Legos, are designed to be mixed and matched at will. Several thousand of these BioBricks, fulfilling various functions, are already housed in the MIT-based Registry of Standard Biological Parts. Some BioBricks detect chemicals like arsenic; others act as “tuners” that determine the threshold level of chemical input needed to turn on a certain gene. By combining the new color-producing genes with existing parts, the thinking went, one might easily construct biosensors that, in the presence of environmental toxins, produce output visible to the naked eye.
“E. chromi” struck a chord with designers Alexandra Daisy Ginsberg, G ’06, and James King, who began a collaboration with the iGEM team. In a short video that was named best documentary at the Bio:Fiction synthetic biology film festival in 2011, Ginsberg and King imagined possible futures for living color. Soon, they suggested, scientists might search the natural world for new biological pigments and the genes responsible, revolutionizing dye production. “E. chromi” in probiotic yogurt might monitor human disease while traveling through the gut; microbes in the atmosphere might change color to indicate air quality.
“I think it’s a new term to most of the public, synthetic biology,” mused the host of National Public Radio’s Science Friday in the fall of 2009 when he interviewed the Cambridge team. “But I guess we’re going to be hearing a lot more of it.”
How to Build a Biological Machine
ARMED with powerful new genetic tools and a penchant for tinkering, synthetic biologists have built a new menagerie. Photographic “E. coliroid” darken in response to light. Sensor bacteria record the presence of a chemical in a mouse’s gut by turning on certain genes. There are strains of E. coli that count input signals and others that carry out logical operations—steps toward biological computers. Still other strains smell like wintergreen and bananas instead of like the human gut. In 2005, festive researchers “wrote” the first verse of Viktor Rydberg’s Christmas poem “Tomten” into the genome of yet another E. coli strain, using triplets of DNA nucleotides to represent each letter; the resulting bacterium, they wrote, was “the first example of an organism that ‘recites’ poetry.”
Insofar as a common theme unites these diverse creations, it is the transformation of biology into an engineering discipline. Traditional genetic engineering amounted more or less to biological cut-and-paste: scientists could, for instance, transfer a cold-tolerance gene from an Arctic fish into a tomato. Synthetic biology aims for a more radical reorganization. Its organisms are built to be biological machines, with DNA and proteins standing in for circuit components or lines of computer code. In combination, the biological parts perform functions unknown to nature: processing signals, producing new chemicals, storing information.
“I like to say that biological carbon is the silicon of this century,” says Pamela A. Silver, Adams professor of biochemistry and systems biology at Harvard Medical School (HMS; see “Biology in This Century,” September-October 2011, page 72). Just as computers revolutionized the past hundred years, she says, biology is poised to transform the next. “The building of biological machines and biological computers—all of that should soon become a reality.”
To a certain mind, a cell already resembles a tiny, complex machine. It takes in chemicals from the environment and performs reactions to build new biological parts; it monitors signals and turns genes on and off in response. Cells have been compared to computers, to factories, to automatons. For a synthetic biologist with such complex systems already at hand, the task is to identify and manipulate the appropriate parts. “Many of the biomolecular components we’re not building from scratch,” says James J. Collins, Warren Distinguished Professor at Boston University and founding core faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering. “We’re taking native systems and then modifying them.”
Understanding and manipulating this elaborate machinery is a tough job. “I think of it as if some alien intelligence just dropped onto us all their intellectual property without documentation,” says George Church, Winthrop professor of genetics at HMS (see “DNA as Data,” January-February 2004, page 44). There’s no direct biological equivalent of a capacitor or the delete command, and synthetic biologists must creatively recombine existing biological parts in order to build new functions.
Take, for instance, the toggle switch, one of the simplest circuit components. A nonbiological example would be a light switch: it can be flipped between two discrete states, on or off, with nothing in between. In an abstract sense, the toggle switch amounts to a kind of memory, with its two states tantamount to 0’s and 1’s. Such bistability has some analogues in nature. Venus fly traps, for instance, have structures that alternate between open and shut (see “Leaves That Lunch,” May-June 2005, page 14). Specific signals instruct cells whether to remain dormant or divide. Some viruses also toggle between two distinct states of dormancy or active infection.
When Collins’s lab built a bacterial toggle switch—one of the first pieces of biological circuitry—they made it from two genes. Each encoded a repressor protein for the opposite gene; once one gene was turned on, it turned the other gene off. The switch could be flipped by giving the cell a specific chemical signal, disabling the active repressor protein and allowing the other to take hold. With the second gene now turned on, turning off the first, the switch would stay flipped long after the signal had disappeared. “As a cellular memory unit,” wrote Collins when his team published its design in 2000, “the toggle forms the basis for ‘genetic applets’—self-contained, programmable, synthetic gene circuits for the control of cell function.”
Genetic applets (perhaps more aptly, apps today) are one of synthetic biology’s defining goals. Some 40 years after scientists began learning to rearrange DNA, genetic engineering remains something of a cottage industry. In a time-consuming, almost artisanal craft, researchers modify organisms ad hoc to suit their particular needs. Synthetic biology was born out of a desire for greater, more versatile control, says Silver, who took part in early meetings of the Synthetic Biology Working Group at MIT. “The question that forms the core of synthetic biology is, ‘Why can’t biology be easier and more predictable to engineer?’ ”
Indeed, for synthetic biologists, it is not enough to have painstakingly built genetic switches and biological machines. “Right now, people—especially graduate students—just spend an inordinate amount of time making DNA and figuring out how to put DNA together,” says Jeffrey Way, senior staff scientist at the Wyss Institute, who is married to Silver. “It’s extremely time-consuming.”