"One of the long-term goals in synthetic biology is the construction of large-scale gene networks to control and manipulate cells. Such networks often tweak natural regulatory mechanisms, or ‘switches’, in order to achieve the desired function. Regulatory mechanisms that involve RNA building blocks such as messenger RNA, microRNA and riboswitches have become increasingly prominent in this regard. Recent achievements include prototype mRNA sensors, logic circuits that respond to small molecule cues to affect cell fate, and cell-state classifier networks that identify physiological states using multiple microRNA inputs. This Review describes these and other results in RNA-based synthetic biology." http://bit.ly/MhMKjn
Cobb RE, Si T, Zhao H. "Synthetic biology, with its goal of designing biological entities for wide-ranging purposes, remains a field of intensive research interest. However, the vast complexity of biological systems has heretofore rendered rational design prohibitively difficult. As a result, directed evolution remains a valuable tool for synthetic biology, enabling the identification of desired functionalities from large libraries of variants. This review highlights the most recent advances in the use of directed evolution in synthetic biology, focusing on new techniques and applications at the pathway and genome scale." http://1.usa.gov/K5fexP
Lukmaan A. Bawazera, Michi Izumib, Dmitriy Kolodinc, James R. Neilsona,, Birgit Schwenzer, and Daniel E. Morse "The way nature evolves and sculpts materials using proteins inspires new approaches to materials engineering but is still not completely understood. Here, we present a cell-free synthetic biological plat- form to advance studies of biologically synthesized solid-state materials. This platform is capable of simultaneously exerting many of the hierarchical levels of control found in natural biomineraliza- tion, including genetic, chemical, spatial, structural, and morpholog- ical control, while supporting the evolutionary selection of new mineralizing proteins and the corresponding genetically encoded materials that they produce. DNA-directed protein expression and enzymatic mineralization occur on polystyrene microbeads in water- in-oil emulsions, yielding synthetic surrogates of biomineralizing cells that are then screened by flow sorting, with light-scattering signals used to sort the resulting mineralized composites differen- tially. We demonstrate the utility of this platform by evolutionarily selecting newly identified silicateins, biomineralizing enzymes pre- viously identified from the silica skeleton of a marine sponge, for enzyme variants capable of synthesizing silicon dioxide (silica) or titanium dioxide (titania) composites. Mineral composites of in- termediate strength are preferentially selected to remain intact for identification during cell sorting, and then to collapse postsorting to expose the encoding genes for enzymatic DNA amplification. Some of the newly selected silicatein variants catalyze the formation of crystalline silicates, whereas the parent silicateins lack this ability. The demonstrated bioengineered route to previously undescribed materials introduces in vitro enzyme selection as a viable strategy for mimicking genetic evolution of materials as it occurs in nature.* http://bit.ly/KLyYY9
"Large protein complexes can be designed and created using smaller protein building blocks that self-assemble. David Baker at the University of Washington, Seattle, and his team report a method for producing such proteins. The authors simulate the docking of protein building blocks in desired architectures and then design amino-acid sequences for these blocks that result in low-energy interfaces between the blocks, driving self-assembly. The researchers incorporate the genes that encode the designed blocks into the bacterium Escherichia coli, which produces the proteins that then spontaneously self-assemble into the target architectures. The team created two cage-like proteins: one consisting of 24 building blocks in a 13-nanometre-wide complex with octahedral symmetry (pictured) and another comprising 12 subunits with an 11-nanometre-wide tetrahedral symmetry."
Karin Betz, Denis A Malyshev, Thomas Lavergne, Wolfram Welte, Kay Diederichs, Tammy J Dwyer, Phillip Ordoukhanian, Floyd E Romesberg & Andreas Marx "Many candidate unnatural DNA base pairs have been developed, but some of the best-replicated pairs adopt intercalated structures in free DNA that are difficult to reconcile with known mechanisms of polymerase recognition. Here we present crystal structures of KlenTaq DNA polymerase at different stages of replication for one such pair, dNaM-d5SICS, and show that efficient replication results from the polymerase itself, inducing the required natural-like structure."
Genetically encoded RNA photoswitches as tools for the control of gene expression.
by Jäschke A. "An important goal in chemical and synthetic biology is controlling the expression of defined sets of genes by external stimuli, and one of the most attractive stimuli is light. Current approaches to the photocontrol of biological processes utilize photoresponsive proteins. In this article, I will illustrate the prospects of synthetic systems in which the receptor is a photoresponsive nucleic acid, and will review the different tools already in place to develop photoresponsive systems based on RNA. A particular focus is on genetically encoded photoswitches that can be expressed in prokaryotic or eukaryotic cells, and respond to photoisomerizable, cell-permeable small molecules."
This article is by Ronald W. Davis, director of the Stanford Genome Technology Center and professor of biochemistry and genetics at the Stanford University School of Medicine.
Vsevolod V. Gurevich, , Eugenia V. Gurevich "Highlights ► Targeted manipulation of cell signaling pathways has high therapeutic potential ► Changed expression of wild type proteins can change cell function ► Reengineered signaling proteins change the flow of information in the cell ► Novel proteins constructed from existing domains modify cell signaling" http://bit.ly/KumVyT
Biliouris K, Babson D, Schmidt-Dannert C, Kaznessis Y. Abstract ABSTRACT: BACKGROUND: The eld of synthetic biology has greatly evolved and numerous functions can now be implemented by articially engineered cells carrying the appropriate genetic information. However, in order for the cells to robustly perform complex or multiple tasks, co-operation between them may be necessary. Therefore, various synthetic biological systems whose functionality requires cell-cell communication are being designed. These systems, microbial consortia, are composed of engineered cells and exhibit a wide range of behaviors. These include yeast cells whose growth is dependent on one another, or bacteria that kill or rescue each other, synchronize, behave as predator-prey ecosystems or invade cancer cells. RESULTS: In this paper, we study a synthetic ecosystem comprising of bacteria and yeast that communicate with and benet from each other using small diffusible molecules. We explore the behavior of this heterogeneous microbial consortium, composed of Saccharomyces cerevisiae and Escherichia coli cells, using stochastic modeling. The stochastic model captures the relevant intra-cellular and inter-cellular interactions taking place in and between the eukaryotic and prokaryotic cells. Integration of well-characterized molecular regulatory elements into these two microbes allows for communication through quorum sensing. A gene controlling growth in yeast is induced by bacteria via chemical signals and vice versa. Interesting dynamics that are common in natural ecosystems, such as obligatory and facultative mutualism, extinction, commensalism and predator-prey like dynamics are observed. We investigate and report on the conditions under which the two species can successfully communicate and rescue each other. CONCLUSIONS: This study explores the various behaviors exhibited by the cohabitation of engineered yeast and bacterial cells. The way that the model is built allows for studying the dynamics of any system consisting of two species communicating with one another via chemical signals. Therefore, key information acquired by our model may potentially drive the experimental design of various synthetic heterogeneous ecosystems." http://1.usa.gov/LCXqoG
*Fine-Tuning Tomato Agronomic Properties by Computational Genome Redesign*
by Javier Carrera, Asun Fernández del Carmen, Rafael Fernández-Muñoz, Jose Luis Rambla, Clara Pons, Alfonso Jaramillo, Santiago F. Elena, Antonio Granell "Considering cells as biofactories, we aimed to optimize its internal processes by using the same engineering principles that large industries are implementing nowadays: lean manufacturing. We have applied reverse engineering computational methods to transcriptomic, metabolomic and phenomic data obtained from a collection of tomato recombinant inbreed lines to formulate a kinetic and constraint-based model that efficiently describes the cellular metabolism from expression of a minimal core of genes. Based on predicted metabolic profiles, a close association with agronomic and organoleptic properties of the ripe fruit was revealed with high statistical confidence. Inspired in a synthetic biology approach, the model was used for exploring the landscape of all possible local transcriptional changes with the aim of engineering tomato fruits with fine-tuned biotechnological properties. The method was validated by the ability of the proposed genomes, engineered for modified desired agronomic traits, to recapitulate experimental correlations between associated metabolites." http://bit.ly/KOq2RH
"The proteins build shells of silicon, titanium dioxide. Scientists have applied genetic engineering to create proteins that can be used to create electronics. They've used the tools of molecular biology and principles of evolution to find proteins that can make new structures of silicon dioxide, commonly found in computer chips, and titanium dioxide, often used in solar cells.
Traditional genetic engineering involves sticking a foreign gene into bacteria and using the bacteria as tiny factories to make the protein encoded by that gene. This approach wouldn’t work for all silica-forming proteins found in marine sponges. The minerals produced by these proteins, which the researchers want to study, can kill the cells.
So Daniel Morse, of the University of California, Santa Barbara, and his colleagues looked to another protein making strategy: synthetic cells with a tiny plastic bead nucleus surrounded by a bubble of oil that acts as a cell membrane.
The scientists attached a piece of DNA to each of the beads, encoding a unique silica-forming protein, or silicatein. This DNA is a random combination of genes from two related silicateins, interspersed with random mutations.
Then the scientists soaked the beads in watery mixture of the bacterial proteins necessary to turn the DNA into silicateins and covered each bead with a thin layer of oil, trapping water and the enzymes inside. With the artificial cell complete, the interior enzymes made the silicateins, which stuck to antibodies covering the bead’s surface......"
"The rise of synthetic biology as a tool to experiment what and what is not feasible is linked mostly to two endeavors: The accelerated pace of both sequencing and synthesis machines. In the sequencing realm, researchers need to change their slides every fifteen days but the most astounding area, i.e. where opportunities for high dimensional data understanding reside, stems from the faster-than-Moore's law cost decrease for these machines....."
Print proteins, lipids and polymers With nano- to micron-sized features
"NanoInk’s Dip Pen Nanolithography® (DPN®) technology is a direct write, tip based lithography technique that does not subject biological materials to destructive forces (such as compression, shear, harsh vacuum, or UV light) which might alter their structure and function. As such, DPN is ideal for printing proteins, DNA/RNA, aptamers, lipids, additional biopolymers and biocompatible polymers at micron and sub-micron scales. With the precision of DPN, these sub-cellular scaled features can be deposited at defined locations in a controlled and consistent manner. This allows for creation of scaffolds for in vitro cell culture studies or tissue engineering work. " http://bit.ly/Mpj6W7
Bacterial signaling systems as platforms for rational design of new generations of biosensors
by Checa SK, Zurbriggen MD, Soncini FC. "Bacterial signal-responsive regulatory circuits have been employed as platform to design and construct whole-cell bacterial biosensors for reporting toxicity. A new generation of biosensors with improved performance and a wide application range has emerged after the application of synthetic biology concepts to biosensor design. Site-directed mutagenesis, directed evolution and domain swapping were applied to upgrade signal detection or to create novel sensor modules. Rewiring of the genetic circuits allows improving the determinations and reduces the heterogeneity of the response between individual reporter cells. Moreover, the assembly of natural or engineered modules to biosensor platforms provides innovative outputs, expanding the range of application of these devises, from monitoring toxics and bioremediation to killing targeted cells." http://1.usa.gov/JTBbQj
Nicole Rusk "With the help of engineered polymerases and reverse transcriptases, synthetic nucleic acids can encode and pass on genetic information. The fact that in biology information flows bidirectionally—from DNA to RNA and then back to DNA—raised a question for Phil Holliger at the Medical Research Council (Cambridge, UK): is there something inherently special about DNA and RNA, or can other polymers exchange information as well?
In the last 30 years, biological chemists have developed a wide range of potential DNA mimics—which Holliger refers to as xeno-nucleic acids (XNA)—that have the ability to hybridize to DNA and RNA: for example, locked nucleic acids, which are widely used as inhibitors of mRNA or microRNAs. But to answer his questions, Holliger needed to go beyond hybridization. “We wanted not just to synthesize polymers but [to] create a replication loop, from DNA to XNA back to DNA,” he says.
His team decided to concentrate on changing the sugar in the nucleic acid rather than the phosphate backbone or the nucleobases. Because they retained the classical nucleobases G, A, T and C, the XNAs also kept the ability to interact with DNA. The researchers swapped the canonical five-membered ribofuranose sugar ring for other structures—for example, hydrohexitol to make hydrohexitol nucleic acids (HNAs). ....."
Stefano Cardinale, Adam Paul Arkin "Despite the efforts that bioengineers have exerted in designing and constructing biological processes that function according to a predetermined set of rules, their operation remains fundamentally circumstantial. The contextual situation in which molecules and single-celled or multi-cellular organisms find themselves shapes the way they interact, respond to the environment and process external information. Since the birth of the field, synthetic biologists have had to grapple with contextual issues, particularly when the molecular and genetic devices inexplicably fail to function as designed when tested in vivo. In this review, we set out to identify and classify the sources of the unexpected divergences between design and actual function of synthetic systems and analyze possible methodologies aimed at controlling, if not preventing, unwanted contextual issues."
To get content containing either thought or leadership enter:
To get content containing both thought and leadership enter:
To get content containing the expression thought leadership enter:
You can enter several keywords and you can refine them whenever you want. Our suggestion engine uses more signals but entering a few keywords here will rapidly give you great content to curate.
Your new post is loading...
