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House Panel Votes to Halt Obama's Internet Power Transfer

House Panel Votes to Halt Obama's Internet Power Transfer | SynBioFromLeukipposInstitute | Scoop.it
Republicans worry Russia or China could seize control of the Internet.
Gerd Moe-Behrens's insight:

http://bit.ly/1lcYd3J

I hope the internet will stay under US control. If I think about  the alternatives, the US will be the most likely guardian for a free internet, despite the recent surveillance scandals. 
Science need a free internet.

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Protein design: I like to fold it, fold it

Protein design: I like to fold it, fold it | SynBioFromLeukipposInstitute | Scoop.it
Most proteins have evolved for function rather than stability, which makes it difficult to ascertain the connections between sequence and folding and, in turn, confounds de novo protein design. Combining the expression of synthetic DNA libraries with proteolysis resistance assays, Rocklin et al. have now systematically determined the stability of over 15,000 designed miniproteins in a high-throughput fashion. Following the screen, each sequence was assigned a 'stability score', and a subset was validated by structural analyses including circular dichroism and NMR
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Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo | SynBioFromLeukipposInstitute | Scoop.it
Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C–Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.
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Performance of objective functions and optimisation procedures for parameter estimation in system biology models

Mathematical modelling of signalling pathways aids experimental investigation in system and synthetic biology. Ever increasing data availability prompts the development of large dynamic models with numerous parameters. In this paper, we investigate how the number of unknown parameters affects the convergence of three frequently used optimisation algorithms and four objective functions. We compare objective functions that use data-driven normalisation of the simulations with those that use scaling factors. The data-driven normalisation of the simulation approach implies that simulations are normalised in the same way as the data, making both directly comparable. The scaling factor approach, which is commonly used for parameter estimation in dynamic systems, introduces scaling factors that multiply the simulations to convert them to the scale of the data. Here we show that the scaling factor approach increases, compared to data-driven normalisation of the simulations, the degree of practical non-identifiability, defined as the number of directions in the parameter space, along which parameters are not identifiable. Further, the results indicate that data-driven normalisation of the simulations greatly improve the speed of convergence of all tested algorithms when the overall number of unknown parameters is relatively large (74 parameters in our test problems). Data-driven normalisation of the simulations also markedly improve the performance of the non-gradient-based algorithm tested even when the number of unknown parameters is relatively small (10 parameters in our test problems). As the models and the unknown parameters increase in size, the data-driven normalisation of the simulation approach can be the preferred option, because it does not aggravate non-identifiability and allows for obtaining parameter estimates in a reasonable amount of time.
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Genome modularity and synthetic biology: Engineering systems

Genome modularity and synthetic biology: Engineering systems | SynBioFromLeukipposInstitute | Scoop.it
Whole genome sequencing projects running in various laboratories around the world has generated immense data. A systematic phylogenetic analysis of this data shows that genome complexity goes on decreasing as it evolves, due to its modular nature. This modularity can be harnessed to minimize the genome further to reduce it with the bare minimum essential genes. A reduced modular genome, can fuel progress in the area of synthetic biology by providing a ready to use plug and play chassis. Advances in gene editing technology such as the use of tailor made synthetic transcription factors will further enhance the availability of synthetic devices to be applied in the fields of environment, agriculture and health.
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Can CRISPR and/or combining it with AI/automation improve research capabilities? If so how? • r/Futurology

Can CRISPR and/or combining it with AI/automation improve research capabilities? If so how? • r/Futurology | SynBioFromLeukipposInstitute | Scoop.it
I see a lot of researcher using CRISPR directly, but what if we let machines do it? What if we code the machines to utilize searchin
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orco Mutagenesis Causes Loss of Antennal Lobe Glomeruli and Impaired Social Behavior in Ants

orco Mutagenesis Causes Loss of Antennal Lobe Glomeruli and Impaired Social Behavior in Ants | SynBioFromLeukipposInstitute | Scoop.it
Life inside ant colonies is orchestrated with diverse pheromones, but it is not clear how ants perceive these social signals. It has been proposed that pheromone perception in ants evolved via expansions in the numbers of odorant receptors (ORs) and antennal lobe glomeruli. Here, we generate the first mutant lines in the clonal raider ant, Ooceraea biroi, by disrupting orco, a gene required for the function of all ORs. We find that orco mutants exhibit severe deficiencies in social behavior and fitness, suggesting they are unable to perceive pheromones. Surprisingly, unlike in Drosophila melanogaster, orco mutant ants also lack most of the ∼500 antennal lobe glomeruli found in wild-type ants. These results illustrate that ORs are essential for ant social organization and raise the possibility that, similar to mammals, receptor function is required for the development and/or maintenance of the highly complex olfactory processing areas in the ant brain.
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Microsoft Plans to Have a DNA-Based Computer by 2020

Microsoft Plans to Have a DNA-Based Computer by 2020 | SynBioFromLeukipposInstitute | Scoop.it
It’s durable, exponentially scalable, and it’ll last millennia, if not millions of years.
 
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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.
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Identifying time-delayed gene regulatory networks via an evolvable hierarchical recurrent neural network

The modeling of genetic interactions within a cell is crucial for a basic understanding of physiology and for applied areas such as drug design. Interactions in gene regulatory networks (GRNs) include effects of transcription factors, repressors, small metabolites, and microRNA species. In addition, the effects of regulatory interactions are not always simultaneous, but can occur after a finite time delay, or as a combined outcome of simultaneous and time delayed interactions. Powerful biotechnologies have been rapidly and successfully measuring levels of genetic expression to illuminate different states of biological systems. This has led to an ensuing challenge to improve the identification of specific regulatory mechanisms through regulatory network reconstructions. Solutions to this challenge will ultimately help to spur forward efforts based on the usage of regulatory network reconstructions in systems biology applications.
METHODS:
We have developed a hierarchical recurrent neural network (HRNN) that identifies time-delayed gene interactions using time-course data. A customized genetic algorithm (GA) was used to optimize hierarchical connectivity of regulatory genes and a target gene. The proposed design provides a non-fully connected network with the flexibility of using recurrent connections inside the network. These features and the non-linearity of the HRNN facilitate the process of identifying temporal patterns of a GRN.
RESULTS:
Our HRNN method was implemented with the Python language. It was first evaluated on simulated data representing linear and nonlinear time-delayed gene-gene interaction models across a range of network sizes and variances of noise. We then further demonstrated the capability of our method in reconstructing GRNs of the Saccharomyces cerevisiae synthetic network for in vivo benchmarking of reverse-engineering and modeling approaches (IRMA). We compared the performance of our method to TD-ARACNE, HCC-CLINDE, TSNI and ebdbNet across different network sizes and levels of stochastic noise. We found our HRNN method to be superior in terms of accuracy for nonlinear data sets with higher amounts of noise.
CONCLUSIONS:
The proposed method identifies time-delayed gene-gene interactions of GRNs. The topology-based advancement of our HRNN worked as expected by more effectively modeling nonlinear data sets. As a non-fully connected network, an added benefit to HRNN was how it helped to find the few genes which regulated the target gene over different time delays.
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Undergrads develop bacteria to fight carcinogens for international competition

Undergrads develop bacteria to fight carcinogens for international competition | SynBioFromLeukipposInstitute | Scoop.it
While some students have been away from campus, a team of six undergraduate students have been creating a bacteria to help reduce the damaging effects of carcinogens.
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Modulating the Phe-Phe dipeptide aggregation landscape via covalent attachment of an azobenzene photoswitch

Synthetic control of peptide-based supramolecular assemblies can provide molecular cues to understand protein aggregation while also inspiring the development of novel chemical biology tools to deliver cargoes inside cells. Here we show that the trans-to-cis photoisomerization of a pendant azo-group covalently attached to a Phe-Phe dipeptide can comprehensively 'turn-off' its native fibrillation propensity as well as provide an optical handle to reversibly switch the aggregate morphology from fibril to vesicle.
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Cell-free extract based optimization of biomolecular circuits with droplet microfluidics

Engineering an efficient biomolecular circuit often requires time-consuming iterations of optimization. Cell-free protein expression systems allow rapid testing of biocircuits in vitro, speeding the design-build-test cycle of synthetic biology. In this paper, we combine this with droplet microfluidics to densely scan a transcription-translation biocircuit space. Our system assays millions of parameter combinations per hour, providing a detailed map of function. The ability to comprehensively map biocircuit parameter spaces allows accurate modeling to predict circuit function and identify optimal circuits and conditions.
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Droplet Microfluidics for Synthetic Biology

Droplet Microfluidics for Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
Synthetic biology is an interdisciplinary field that aims to engineer biological systems for useful purposes. Organism engineering often requires the optimization of individual genes and/or entire biological pathways (consisting of multiple genes). Advances in DNA sequencing and synthesis have recently begun to enable the possibility of evaluating thousands of gene variants and hundreds of thousands of gene combinations. However, such large-scale optimization experiments remain cost-prohibitive to researchers following traditional molecular biology practices, which are frequently labor-intensive and suffer from poor reproducibility. Liquid handling robotics may reduce labor and improve reproducibility, but are themselves expensive and thus inaccessible to most researchers. Microfluidic platforms offer a lower entry price point alternative to robotics, and maintain high throughput and reproducibility while further reducing operating costs through diminished reagent volume requirements. Droplet microfluidics have shown exceptional promise for synthetic biology experiments, including DNA assembly, transformation/transfection, culturing, cell sorting, phenotypic assays, artificial cells and genetic circuits.
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Bacterial machines that help create defensive 'mats' mapped by researchers

Bacterial machines that help create defensive 'mats' mapped by researchers | SynBioFromLeukipposInstitute | Scoop.it
The way that some bacteria produce the materials that form 'biofilms', which help them evade antibiotic attack, has been uncovered by scientists.

The latest finding could eventually lead to new ways of getting around antibiotic resistance and help in making new, biologically inspired nanomaterials.

When bacteria are stressed, for example when attacked by the immune system or antibiotics, they can club together and form a biofilm. Biofilms can also affect water quality and ‘foul’ surfaces in industrial settings, damaging their performance.
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Cambridge Synthetic Biology Meetup

Going deeper with deep sequencing and deep learning Biomakespace

Tuesday, Aug 22, 2017, 7:00 PM

Biomakespace
Bay 13, Cambridge Biomedical Campus, Hills Road, CB2 0SP Cambridge, GB

5 Members Attending

In this week's Lab it Tuesday meetup at the Biomakespace, we discuss deep sequencing and deep learning. Deep sequencing is one of the most powerful biological tools that we have to date, and it can generate millions of pieces of biological data. On the other hand, deep learning is an advanced computing algorithm that is great at analysing big data....

Check out this Meetup →

In this week's Lab it Tuesday meetup at the Biomakespace, we discuss deep sequencing and deep learning.
Deep sequencing is one of the most powerful biologi
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7 TED Talks on biohacking

7 TED Talks on biohacking | SynBioFromLeukipposInstitute | Scoop.it
Satisfy your curiosity on a cellular level with these talks that highlight the ways biology can be molded in the hands of the average, yet curious citizen.
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An Engineered orco Mutation Produces Aberrant Social Behavior and Defective Neural Development in Ants

An Engineered orco Mutation Produces Aberrant Social Behavior and Defective Neural Development in Ants | SynBioFromLeukipposInstitute | Scoop.it
Ants exhibit cooperative behaviors and advanced forms of sociality that depend on pheromone-mediated communication. Odorant receptor neurons (ORNs) express specific odorant receptors (ORs) encoded by a dramatically expanded gene family in ants. In most eusocial insects, only the queen can transmit genetic information, restricting genetic studies. In contrast, workers in Harpegnathos saltator ants can be converted into gamergates (pseudoqueens) that can found entire colonies. This feature facilitated CRISPR-Cas9 generation of germline mutations in orco, the gene that encodes the obligate co-receptor of all ORs. orco mutations should significantly impact olfaction. We demonstrate striking functions of Orco in odorant perception, reproductive physiology, and social behavior plasticity. Surprisingly, unlike in other insects, loss of OR functionality also dramatically impairs development of the antennal lobe to which ORNs project. Therefore, the development of genetics in Harpegnathos establishes this ant species as a model organism to study the complexity of eusociality.
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Intracellular signaling in CRISPR-Cas defense

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated protein) system is known to protect bacteria against foreign invading DNA, usually from phages (viruses that infect bacteria) or plasmids (circular DNA found in the cytoplasm of bacteria). Since the first demonstration of CRISPR-Cas functionality a decade ago (1), mechanistic understanding of CRISPR-Cas has not only enabled genome editing but also revolutionized our appreciation of bacterial defense against their viruses. CRISPR-Cas systems show a high degree of sophistication in providing immunity against phages, including elaborate mechanisms to accurately identify the invading DNA, safety checks to prevent self-targeting (2), and high diversity of target destruction mechanisms among different types of CRISPR-Cas systems (3). Kazlauskiene et al. (4), on page 605 of this issue, and a study by Niewoehner et al. (5) report the discovery of an unexpected aspect of CRISPR-Cas immunity: intracellular signaling.
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An Engineered Optogenetic Switch for Spatiotemporal Control of Gene Expression, Cell Differentiation, and Tissue Morphogenesis

The precise spatial and temporal control of gene expression, cell differentiation, and tissue morphogenesis has widespread application in regenerative medicine and the study of tissue development. In this work, we applied optogenetics to control cell differentiation and new tissue formation. Specifically, we engineered an optogenetic "on" switch that provides permanent transgene expression following a transient dose of blue light illumination. To demonstrate its utility in controlling cell differentiation and reprogramming, we incorporated an engineered form of the master myogenic factor MyoD into this system in multipotent cells. Illumination of cells with blue light activated myogenic differentiation, including upregulation of myogenic markers and fusion into multinucleated myotubes. Cell differentiation was spatially patterned by illumination of cell cultures through a photomask. To demonstrate the application of the system to controlling in vivo tissue development, the light inducible switch was used to control the expression of VEGF and angiopoietin-1, which induced angiogenic sprouting in a mouse dorsal window chamber model. Live intravital microscopy showed illumination-dependent increases in blood-perfused microvasculature. This optogenetic switch is broadly useful for applications in which sustained and patterned gene expression is desired following transient induction, including tissue engineering, gene therapy, synthetic biology, and fundamental studies of morphogenesis.
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Modeling and simulation of biological systems using SPICE language

Modeling and simulation of biological systems using SPICE language | SynBioFromLeukipposInstitute | Scoop.it
The article deals with BB-SPICE (SPICE for Biochemical and Biological Systems), an extension of the famous Simulation Program with Integrated Circuit Emphasis (SPICE). BB-SPICE environment is composed of three modules: a new textual and compact description formalism for biological systems, a converter that handles this description and generates the SPICE netlist of the equivalent electronic circuit and NGSPICE which is an open-source SPICE simulator. In addition, the environment provides back and forth interfaces with SBML (System Biology Markup Language), a very common description language used in systems biology. BB-SPICE has been developed in order to bridge the gap between the simulation of biological systems on the one hand and electronics circuits on the other hand. Thus, it is suitable for applications at the interface between both domains, such as development of design tools for synthetic biology and for the virtual prototyping of biosensors and lab-on-chip. Simulation results obtained with BB-SPICE and COPASI (an open-source software used for the simulation of biochemical systems) have been compared on a benchmark of models commonly used in systems biology. Results are in accordance from a quantitative viewpoint but BB-SPICE outclasses COPASI by 1 to 3 orders of magnitude regarding the computation time. Moreover, as our software is based on NGSPICE, it could take profit of incoming updates such as the GPU implementation, of the coupling with powerful analysis and verification tools or of the integration in design automation tools (synthetic biology).
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Ultrasonic vibrations force a polymer to be a semiconductor

Ultrasonic vibrations force a polymer to be a semiconductor | SynBioFromLeukipposInstitute | Scoop.it
(Phys.org)—A team of researchers at Stanford University has used mechanical force to transform a molecule from one form to another—from a nonconductive state into a semiconductor. In their paper published in the journa
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A modular yeast biosensor for low-cost point-of-care pathogen detection

The availability of simple, specific, and inexpensive on-site detection methods is of key importance for deployment of pathogen surveillance networks. We developed a nontechnical and highly specific colorimetric assay for detection of pathogen-derived peptides based on Saccharomyces cerevisiae-a genetically tractable model organism and household product. Integrating G protein-coupled receptors with a visible, reagent-free lycopene readout, we demonstrate differential detection of major human, plant, and food fungal pathogens with nanomolar sensitivity. We further optimized a one-step rapid dipstick prototype that can be used in complex samples, including blood, urine, and soil. This modular biosensor can be economically produced at large scale, is not reliant on cold-chain storage, can be detected without additional equipment, and is thus a compelling platform scalable to global surveillance of pathogens.
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Ultrasonic vibrations force a polymer to be a semiconductor

Ultrasonic vibrations force a polymer to be a semiconductor | SynBioFromLeukipposInstitute | Scoop.it
(Phys.org)—A team of researchers at Stanford University has used mechanical force to transform a molecule from one form to another—from a nonconductive state into a semiconductor. In their paper published in the journal Science, the group describes the process they developed and possible applications.
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