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Synthetic genetics

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https://www.readbyqxmd.com/read/27911359/directed-protein-packaging-within-outer-membrane-vesicles-from-escherichia-coli-design-production-and-purification
#1
Nathan J Alves, Kendrick B Turner, Scott A Walper
An increasing interest in applying synthetic biology techniques to program outer membrane vesicles (OMV) are leading to some very interesting and unique applications for OMV where traditional nanoparticles are proving too difficult to synthesize. To date, all Gram-negative bacteria have been shown to produce OMV demonstrating packaging of a variety of cargo that includes small molecules, peptides, proteins and genetic material. Based on their diverse cargo, OMV are implicated in many biological processes ranging from cell-cell communication to gene transfer and delivery of virulence factors depending upon which bacteria are producing the OMV...
November 16, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27908266/is-metformin-a-perfect-drug-updates-in-pharmacokinetics-and-pharmacodynamics
#2
Magdalena Markowicz-Piasecka, Kristiina Maria Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27907045/pulse-detecting-genetic-circuit-a-new-design-approach
#3
Nasimul Noman, Mara Inniss, Hitoshi Iba, Jeffrey C Way
A robust cellular counter could enable synthetic biologists to design complex circuits with diverse behaviors. The existing synthetic-biological counters, responsive to the beginning of the pulse, are sensitive to the pulse duration. Here we present a pulse detecting circuit that responds only at the falling edge of a pulse-analogous to negative edge triggered electric circuits. As biological events do not follow precise timing, use of such a pulse detector would enable the design of robust asynchronous counters which can count the completion of events...
2016: PloS One
https://www.readbyqxmd.com/read/27905091/recent-advances-of-molecular-toolbox-construction-expand-pichia-pastoris-in-synthetic-biology-applications
#4
REVIEW
Zhen Kang, Hao Huang, Yunfeng Zhang, Guocheng Du, Jian Chen
Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P...
January 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27903912/the-complex-evolutionary-history-of-aminoacyl-trna-synthetases
#5
Anargyros Chaliotis, Panayotis Vlastaridis, Dimitris Mossialos, Michael Ibba, Hubert D Becker, Constantinos Stathopoulos, Grigorios D Amoutzias
Aminoacyl-tRNA synthetases (AARSs) are a superfamily of enzymes responsible for the faithful translation of the genetic code and have lately become a prominent target for synthetic biologists. Our large-scale analysis of >2500 prokaryotic genomes reveals the complex evolutionary history of these enzymes and their paralogs, in which horizontal gene transfer played an important role. These results show that a widespread belief in the evolutionary stability of this superfamily is misconceived. Although AlaRS, GlyRS, LeuRS, IleRS, ValRS are the most stable members of the family, GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genomes...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903826/synthetic-biology-approaches-to-biological-containment-pre-emptively-tackling-potential-risks
#6
REVIEW
Leticia Torres, Antje Krüger, Eszter Csibra, Edoardo Gianni, Vitor B Pinheiro
Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27903825/synthetic-biology-routes-to-bio-artificial-intelligence
#7
REVIEW
Darren N Nesbeth, Alexey Zaikin, Yasushi Saka, M Carmen Romano, Claudiu V Giuraniuc, Oleg Kanakov, Tetyana Laptyeva
The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular 'teachers' and 'students' is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27903821/construction-of-a-minimal-genome-as-a-chassis-for-synthetic-biology
#8
REVIEW
Bong Hyun Sung, Donghui Choe, Sun Chang Kim, Byung-Kwan Cho
Microbial diversity and complexity pose challenges in understanding the voluminous genetic information produced from whole-genome sequences, bioinformatics and high-throughput '-omics' research. These challenges can be overcome by a core blueprint of a genome drawn with a minimal gene set, which is essential for life. Systems biology and large-scale gene inactivation studies have estimated the number of essential genes to be ∼300-500 in many microbial genomes. On the basis of the essential gene set information, minimal-genome strains have been generated using sophisticated genome engineering techniques, such as genome reduction and chemical genome synthesis...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27903818/properties-of-alternative-microbial-hosts-used-in-synthetic-biology-towards-the-design-of-a-modular-chassis
#9
REVIEW
Juhyun Kim, Manuel Salvador, Elizabeth Saunders, Jaime González, Claudio Avignone-Rossa, Jose Ignacio Jiménez
The chassis is the cellular host used as a recipient of engineered biological systems in synthetic biology. They are required to propagate the genetic information and to express the genes encoded in it. Despite being an essential element for the appropriate function of genetic circuits, the chassis is rarely considered in their design phase. Consequently, the circuits are transferred to model organisms commonly used in the laboratory, such as Escherichia coli, that may be suboptimal for a required function...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27902790/accuracy-of-genomic-prediction-in-a-commercial-perennial-ryegrass-breeding-program
#10
Dario Fè, Bilal H Ashraf, Morten G Pedersen, Luc Janss, Stephen Byrne, Niels Roulund, Ingo Lenk, Thomas Didion, Torben Asp, Christian S Jensen, Just Jensen
The implementation of genomic selection (GS) in plant breeding, so far, has been mainly evaluated in crops farmed as homogeneous varieties, and the results have been generally positive. Fewer results are available for species, such as forage grasses, that are grown as heterogenous families (developed from multiparent crosses) in which the control of the genetic variation is far more complex. Here we test the potential for implementing GS in the breeding of perennial ryegrass ( L.) using empirical data from a commercial forage breeding program...
November 2016: Plant Genome
https://www.readbyqxmd.com/read/27902432/self-replicating-shuttle-vectors-based-on-pans-a-small-endogenous-plasmid-of-the-unicellular-cyanobacterium-synechococcus-elongatus-pcc-7942
#11
You Chen, Arnaud Taton, Michaela Go, Ross E London, Lindsey M Pieper, Susan S Golden, James W Golden
To facilitate development of synthetic biology tools for genetic engineering of cyanobacterial strains, we constructed pANS-derived self-replicating shuttle vectors that are based on the minimal replication element of the Synechococcus elongatus strain PCC 7942 plasmid pANS. To remove the possibility of homologous recombination events between the shuttle plasmids and the native pANS plasmid, the endogenous pANS was cured through plasmid incompatibility-mediated spontaneous loss. A heterologous toxin-antitoxin cassette was incorporated into the shuttle vectors for stable plasmid maintenance in the absence of antibiotic selection...
October 14, 2016: Microbiology
https://www.readbyqxmd.com/read/27899650/a-cas9-based-toolkit-to-program-gene-expression-in-saccharomyces-cerevisiae
#12
Amanda Reider Apel, Leo d'Espaux, Maren Wehrs, Daniel Sachs, Rachel A Li, Gary J Tong, Megan Garber, Oge Nnadi, William Zhuang, Nathan J Hillson, Jay D Keasling, Aindrila Mukhopadhyay
Despite the extensive use of Saccharomyces cerevisiae as a platform for synthetic biology, strain engineering remains slow and laborious. Here, we employ CRISPR/Cas9 technology to build a cloning-free toolkit that addresses commonly encountered obstacles in metabolic engineering, including chromosomal integration locus and promoter selection, as well as protein localization and solubility. The toolkit includes 23 Cas9-sgRNA plasmids, 37 promoters of various strengths and temporal expression profiles, and 10 protein-localization, degradation and solubility tags...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896920/fusion-of-ssm6a-with-a-protein-scaffold-retains-selectivity-on-nav-1-7-and-improves-its-therapeutic-potential-against-chronic-pain
#13
Chuan Wang, Bin Shan, Qiong Wang, Qunyuan Xu, Hailin Zhang, Huimeng Lei
Voltage gated sodium channel NaV 1.7 serves an attractive target for chronic pain treatment. Several venom peptides were found to selectively inhibit NaV 1.7 but with intrinsic problems. Among them, Ssm6a, a recently discovered centipede venom peptide, shows the greatest selectivity against NaV 1.7, but dissociates from the target too fast and loses bioactivity in synthetic forms. As a disulfide-rich venom peptide, it is difficult to optimize Ssm6a by artificial mutagenesis and produce the peptide with common industrial manufacturing methods...
November 29, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27894692/the-ex-vivo-l-cbmn-assay-detects-significant-human-exposure-to-butadiene
#14
REVIEW
Claudia Bolognesi, Micheline Kirsch-Volders
1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in rodents revealed widely different BD carcinogenic/mutagenic potency in rat and mice, associated to differences in BD metabolism...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27892516/in-vivo-coherent-raman-imaging-of-the-melanomagenesis-associated-pigment-pheomelanin
#15
Hequn Wang, Sam Osseiran, Vivien Igras, Alexander J Nichols, Elisabeth M Roider, Joachim Pruessner, Hensin Tsao, David E Fisher, Conor L Evans
Melanoma is the most deadly form of skin cancer with a yearly global incidence over 232,000 patients. Individuals with fair skin and red hair exhibit the highest risk for developing melanoma, with evidence suggesting the red/blond pigment known as pheomelanin may elevate melanoma risk through both UV radiation-dependent and -independent mechanisms. Although the ability to identify, characterize, and monitor pheomelanin within skin is vital for improving our understanding of the underlying biology of these lesions, no tools exist for real-time, in vivo detection of the pigment...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883070/ph-responsive-virus-like-nanoparticles-with-enhanced-tumour-targeting-ligands-for-cancer-drug-delivery
#16
Roya Biabanikhankahdani, Noorjahan Banu Mohamed Alitheen, Kok Lian Ho, Wen Siang Tan
Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882539/in-vitro-suppression-of-two-different-stop-codons
#17
Eden Ozer, Yonatan Chemla, Orr Schlesinger, Haim Yuval Aviram, Inbal Riven, Gilad Haran, Lital Alfonta
Proteins play a crucial role in all living organisms, with the twenty natural amino acids as their building blocks. Unnatural amino acids are synthetic derivatives of these natural building blocks. These amino acids have unique chemical or physical properties as a result of their specific side chain residues. Their incorporation into proteins through ribosomal translation in response to one of the stop codons has opened a new way to manipulate and study proteins by enabling new functionalities, thus expending the genetic code...
November 24, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27881725/tata-box-insertion-provide-a-selected-mechanism-for-enhancing-gene-expression-to-adapt-fe-deficiency
#18
Meiling Zhang, Yuanda Lv, Yi Wang, Jocelyn K C Rose, Fei Shen, Zhenyun Han, Xinzhong Zhang, Xuefeng Xu, Ting Wu, Zhenhai Han
Intraspecific genetic variation is essential for plant responses and adaption to evolutionary challenges, such as changing environmental conditions. The development the Earth's aerobic atmosphere has increased the iron (Fe) demand of organisms and Fe deficiency has become a limiting environmental factor for plant growth. We demonstrate here that the adaptation of apple trees to Fe deficiency is achieved by the modification of the promoter of the Iron-Regulated Transporter1 (IRT1) gene. Specifically, an IRT1 mutant allele with a TATA-box insertion in the promoter upstream of the IRT1 coding region enhances IRT1 expression...
November 23, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27879333/the-genome-wide-interaction-network-of-nutrient-stress-genes-in-escherichia-coli
#19
Jean-Philippe Côté, Shawn French, Sebastian S Gehrke, Craig R MacNair, Chand S Mangat, Amrita Bharat, Eric D Brown
: Conventional efforts to describe essential genes in bacteria have typically emphasized nutrient-rich growth conditions. Of note, however, are the set of genes that become essential when bacteria are grown under nutrient stress. For example, more than 100 genes become indispensable when the model bacterium Escherichia coli is grown on nutrient-limited media, and many of these nutrient stress genes have also been shown to be important for the growth of various bacterial pathogens in vivo To better understand the genetic network that underpins nutrient stress in E...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27879131/spatio-temporal-models-of-synthetic-genetic-oscillators
#20
Cicely K Macnamara, Mark A J Chaplain
Signal transduction pathways play a major role in many important aspects of cellular function e.g. cell division, apoptosis. One important class of signal transduction pathways is gene regulatory networks (GRNs). In many GRNs, proteins bind to gene sites in the nucleus thereby altering the transcription rate. Such proteins are known as transcription factors. If the binding reduces the transcription rate there is a negative feedback leading to oscillatory behaviour in mRNA and protein levels, both spatially (e...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
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