SynBioFromLeukipposInstitute

by
Arpino JA, Hancock EJ, Anderson J, Barahona M, Stan GB, Papachristodoulou A, Polizzi K.

"Synthetic Biology is the "Engineering of Biology" - it aims to use a forward-engineering design cycle based on specifications, modelling, analysis, experimental implementation, testing and validation to modify natural or design new, synthetic biology systems so that they behave in a predictable fashion. Motivated by the need for truly plug-and-play synthetic biological components we present a comprehensive review of ways in which the various parts of a biological system can be modified systematically. In particular, we review the list of 'dials' that are available to the designer and discuss how they can be modelled, tuned and implemented. The dials are categorized according to whether they operate at the global, transcriptional, translational or post translational level and the resolution that they operate at. We end this review with a discussion on the relative advantages and disadvantages of some dials over others."
 http://1.usa.gov/13RS9qm

http://bit.ly/1a8g2Kx

by
Karig DK, Jung SY, Srijanto B, Collier CP, Simpson ML.

"Cell-free systems offer a simplified and flexible context that enables important biological reactions while removing complicating factors such as fitness, division, and mutation that are associated with living cells. However, cell-free expression in unconfined spaces is missing important elements of expression in living cells. In particular, the small volume of living cells can give rise to significant stochastic effects, which are negligible in bulk cell-free reactions. Here, we confine cell-free gene expression reactions to cell-relevant 20 fL volumes (between the volumes of E. coli and S. cerevisiae), in polydimethylsiloxane (PDMS) containers. We demonstrate that expression efficiency varies widely among different containers, likely due to non-Poisson distribution of expression machinery at the observed scale. Previously, this phenomenon has been observed only in liposomes. In addition, we analyze gene expression noise. This analysis is facilitated by our use of cell-free systems, which allow the mapping of the measured noise properties to intrinsic noise models. In contrast, previous live cell noise analysis efforts have been complicated by multiple noise sources. Noise analysis reveals signatures of translational bursting while noise dynamics suggest that overall cell-free expression is limited by a diminishing translation rate. In addition to offering a unique approach to understanding noise in gene circuits, our work contributes to a deeper understanding of the biophysical properties of cell-free expression systems, thus aiding efforts to harness cell-free systems for synthetic biology applications."

http://bit.ly/10MxX3T

PhD Thesis

by
Ilaria Anna Colussi

http://bit.ly/18g21LE

by

Gi Na Lee and Jonguk Na 

"Synthetic biology has recently been at the center of the world’s attention as a new scientific and engineering discipline. It allows us to design and construct finely controllable metabolic and regulatory pathways, circuits, and networks, as well as create new enzymes, pathways, and even whole cells. With this great power of synthetic biology, we can develop new organisms that can efficiently produce new drugs to benefit human healthcare and superperforming microorganisms capable of producing chemicals, fuels, and materials from renewable biomass, without the use of fossil oil. Based on several successful examples reported, this commentary aims at peeking into the potential of synthetic biology."

http://bit.ly/18g0Pb4

A single phosphatase can convert a robust step response into a graded, tuneable or adaptive response http://1.usa.gov/12DWGda

*RNAiFold: a web server for RNA inverse folding and molecular design* 

by
JUAN ANTONIO GARCIA-MARTIN

"Synthetic biology is a rapidly emerging discipline with long-term ramifications that range from single-molecule detection within cells to the creation of synthetic genomes and novel life forms. Truly phenomenal results have been obtained by pioneering groups — for instance, the combinatorial synthesis of genetic networks, genome synthesis using BioBricks, and hybridization chain reaction (HCR), in which stable DNA monomers assemble only upon exposure to a target DNA fragment, biomolecular self-assembly pathways, etc. Such work strongly suggests that nanotechnology and synthetic biology together seem poised to constitute the most transformative development of the 21st century. In this paper, we present a Constraint Programming (CP) approach to solve the RNA inverse folding problem. Given a target RNA secondary structure, we determine an RNA sequence which folds into the target structure; i.e. whose minimum free energy structure is the target structure. Our approach represents a step forward in RNA design — we produce the first complete RNA inverse folding approach which allows for the specification of a wide range of design constraints. We also introduce a Large Neighborhood Search approach which allows us to tackle larger instances at the cost of losing completeness, while retaining the advantages of meeting design constraints (motif, GC-content, etc.). Results demonstrate that our software, RNAiFold, performs as well or better than all state-of-the-art approaches; nevertheless, our approach is unique in terms of completeness, flexibility, and the support of various design constraints. The algorithms presented in this paper are publicly available via the interactive webserver http://bioinformatics.bc.edu/clotelab/RNAiFold; additionally, the source code can be downloaded from that site."


http://bit.ly/18oExnA

Synthetic Polymers for Simultaneous Bacterial Sequestration and Quorum Sense Interference http://bit.ly/10lJE6k

by
Folcher M, Xie M, Spinnler A, Fussenegger M.

"Synthetic biology has significantly advanced the design of synthetic control devices, gene circuits and networks that can reprogram mammalian cells in a trigger-inducible manner. Prokaryotic helix-turn-helix motifs have become the standard resource to design synthetic mammalian transcription factors that tune chimeric promoters in a small molecule-responsive manner. We have identified a family of Actinomycetes transcriptional repressor proteins showing a tandem TetR-family signature and have used a synthetic biology-inspired approach to reveal the potential control dynamics of these bi-partite regulators. Daisy-chain assembly of well-characterized prokaryotic repressor proteins such as TetR, ScbR, TtgR or VanR and fusion to either the Herpes simplex transactivation domain VP16 or the Krueppel-associated box domain (KRAB) of the human kox-1 gene resulted in synthetic bi- and even tri-partite mammalian transcription factors that could reversibly program their individual chimeric or hybrid promoters for trigger-adjustable transgene expression using tetracycline (TET), γ-butyrolactones, phloretin and vanillic acid. Detailed characterization of the bi-partite ScbR-TetR-VP16 (ST-TA) transcription factor revealed independent control of TET- and γ-butyrolactone-responsive promoters at high and double-pole double-throw (DPDT) relay switch qualities at low intracellular concentrations. Similar to electromagnetically operated mechanical DPDT relay switches that control two electric circuits by a fully isolated low-power signal, TET programs ST-TA to progressively switch from TetR-specific promoter-driven expression of transgene one to ScbR-specific promoter-driven transcription of transgene two while ST-TA flips back to exclusive transgene 1 expression in the absence of the trigger antibiotic. We suggest that natural repressors and activators with tandem TetR-family signatures may also provide independent as well as DPDT-mediated control of two sets of transgenes in bacteria, and that their synthetic transcription-factor analogs may enable the design of compact therapeutic gene circuits for gene and cell-based therapies."

http://bit.ly/1666XFG

 http://bit.ly/119A8OV

Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro http://bit.ly/13IVtUM