"The design process of complex systems in all the fields of engineering requires a set of quantitatively characterized components and a method to predict the output of systems composed by such elements. This strategy relies on the modularity of the used components or the prediction of their context-dependent behaviour, when parts functioning depends on the specific context. Mathematical models usually support the whole process by guiding the selection of parts and by predicting the output of interconnected systems. Such bottom-up design process cannot be trivially adopted for biological systems engineering, since parts function is hard to predict when components are reused in different contexts. This issue and the intrinsic complexity of living systems limit the capability of synthetic biologists to predict the quantitative behaviour of biological systems. The high potential of synthetic biology strongly depends on the capability of mastering this issue. This review discusses the predictability issues of basic biological parts (promoters, ribosome binding sites, coding sequences, transcriptional terminators, and plasmids) when used to engineer simple and complex gene expression systems in Escherichia coli. A comparison between bottom-up and trial-and-error approaches is performed for all the discussed elements and mathematical models supporting the prediction of parts behaviour are illustrated."
As you might know, I am CEO of a startup called CytoComp http://www.cytocomp.com We are focusing on building a microprocessor from biological parts.
I am interested to build the company structure in a decentralized manner. I would like to discuss how one can do this on top of Ethereum https://www.ethereum.org. Especially interesting subjects are IP, crowd sourced project development, micro payments for crowd sourced micro contributions, distributed location of coworkers, crowd funding of project ideas, crowd shares, contracts, in general tot figure out how a working company structure on top of Ethereum will look like.
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."
I am following tight the developments at Reddcoin - I think their idea of a social currency where you can show your love of a contributor in social media with a tip. Today ReddCoin announced a paper where they further develop their ideas.
A new social currency model by Reddit - this can potentially revolutionize science publishing. We can direct publish and can get payment, if we have done great work - instead of that the authors have to pay and publishing companies make the big money....
*Proof of Stake Velocity: Building the Social Currency of the Digital Age*
by Larry Ren
"Proof of Stake Velocity (PoSV) is proposed as an alternative to Proof of Work (PoW) and Proof of Stake (PoS) to secure the peer-to-peer network and confirm transactions of Reddcoin, a cryptocurrency created specifi- cally to facilitate social interactions in the digital age. PoSV is designed to encourage both ownership (Stake) and activity (Velocity) which directly correspond to the two main functions of Reddcoin as a real currency: store of value and medium of exchange. Reddcoin can also function as the unit of account in heterogeneous social context. The technological aspects of PoSV are presented after a detailed review of existing designs. The eco- nomic aspects of Reddcoin are then analysed. Finally the unique position of Reddcoin as a digital social currency in the competitive landscape of cryptocurrencies is discussed."
Synbiota Inc. 35 Liberty St. Suite #105 Toronto, ON
13 biophilians Attending
Heya DIYbio.to family! I’m pleased to announce two wetlab workshops I’m organizing that will run in September. We’re going to do a DIYbio.to #ScienceHack See https://sciencehack.synbiota.com/
These wetlab workshops involve learning: (1) how to rationally design DNA, assemble your DNA design using real DNA, and; (2) then booting up your assembled DN...
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."