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Synthetic genetics

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https://www.readbyqxmd.com/read/28346455/collective-helicity-switching-of-a-dna-coat-assembly
#1
Yongju Kim, Huichang Li, Ying He, Xi Chen, Xiaoteng Ma, Myongsoo Lee
Hierarchical assemblies of biomolecular subunits can carry out versatile tasks at the cellular level with remarkable spatial and temporal precision. As an example, the collective motion and mutual cooperation between complex protein machines mediate essential functions for life, such as replication, synthesis, degradation, repair and transport. Nucleic acid molecules are far less dynamic than proteins and need to bind to specific proteins to form hierarchical structures. The simplest example of these nucleic acid-based structures is provided by a rod-shaped tobacco mosaic virus, which consists of genetic material surrounded by coat proteins...
March 27, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28346447/synthetic-control-of-flowering-in-rice-independent-of-the-cultivation-environment
#2
Ryo Okada, Yasue Nemoto, Naokuni Endo-Higashi, Takeshi Izawa
For genetically homogeneous crops, the timing of flowering is determined largely by the cultivation environment and is strongly associated with the yield and quality of the harvest(1). Flowering time and other agronomical traits are often tightly correlated, which can lead to difficulty excluding the effects of flowering time when evaluating the characteristics of different genetic varieties(2). Here, we describe the development of transgenic rice plants whose flowering time can be controlled by specific agrochemicals...
March 27, 2017: Nature Plants
https://www.readbyqxmd.com/read/28343170/mirnas-single-nucleotide-polymorphisms-snps-and-age-related-macular-degeneration-amd
#3
John Paul SanGiovanni, Peter M SanGiovanni, Przemysław Sapieha, Vincent De Guire
Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD. The presence of certain single nucleotide polymorphisms (SNPs) may influence the explanatory value of these biomarkers. Here we present findings from an integrated approach used to determine whether AAMD-associated SNPs have the capacity to influence miRNA-mRNA pairing and, if so, to what extent such pairing may be manifested in a discrete AAMD transcriptome...
March 27, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28335420/efforts-and-challenges-in-engineering-the-genetic-code
#4
REVIEW
Xiao Lin, Allen Chi Shing Yu, Ting Fung Chan
This year marks the 48th anniversary of Francis Crick's seminal work on the origin of the genetic code, in which he first proposed the "frozen accident" hypothesis to describe evolutionary selection against changes to the genetic code that cause devastating global proteome modification. However, numerous efforts have demonstrated the viability of both natural and artificial genetic code variations. Recent advances in genetic engineering allow the creation of synthetic organisms that incorporate noncanonical, or even unnatural, amino acids into the proteome...
March 14, 2017: Life
https://www.readbyqxmd.com/read/28325812/thecellmap-org-a-web-accessible-database-for-visualizing-and-mining-the-global-yeast-genetic-interaction-network
#5
Matej Usaj, Yizhao Tan, Wen Wang, Benjamin VanderSluis, Albert Zou, Chad L Myers, Michael Costanzo, Brenda Andrews, Charles Boone
Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore and functionally annotate genetic interactions, or to extract and reorganize sub-networks, using data-driven network layouts in an intuitive and interactive manner...
March 21, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28324236/efficient-de-novo-synthesis-of-resveratrol-by-metabolically-engineered-escherichia-coli
#6
Junjun Wu, Peng Zhou, Xia Zhang, Mingsheng Dong
Resveratrol has been the subject of numerous scientific investigations due to its health-promoting activities against a variety of diseases. However, developing feasible and efficient microbial processes remains challenging owing to the requirement of supplementing expensive phenylpropanoic precursors. Here, various metabolic engineering strategies were developed for efficient de novo biosynthesis of resveratrol. A recombinant malonate assimilation pathway from Rhizobium trifolii was introduced to increase the supply of the key precursor malonyl-CoA and simultaneously, the clustered regularly interspaced short palindromic repeats interference system was explored to down-regulate fatty acid biosynthesis pathway to inactivate the malonyl-CoA consumption pathway...
March 21, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28323531/mitophagy-receptor-fundc1-regulates-mitochondrial-homeostasis-and-protects-the-heart-from-i-r-injury
#7
Weilin Zhang, Sami Siraj, Rong Zhang, Quan Chen
Mitophagy plays pivotal roles in the selective disposal of unwanted mitochondria, and accumulation of damaged mitochondria has been linked to ageing-related diseases. However, definitive proof that mitophagy regulates mitochondrial quality in vivo is lacking. It is also largely unclear whether damaged mitochondria are the cause or just the consequence of these diseases. We previously showed that FUNDC1 is a mitophagy receptor that interacts with LC3 to mediate mitophagy in response to hypoxia in cultured cells...
March 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28321779/transfection-of-bovine-fetal-fibroblast-with-polyethylenimine-pei-nanoparticles-effect-of-particle-size-and-presence-of-fetal-bovine-serum-on-transgene-delivery-and-cytotoxicity
#8
D O Forcato, A E Fili, F E Alustiza, J M Lázaro Martínez, S Bongiovanni Abel, M F Olmos Nicotra, A P Alessio, N Rodríguez, C Barbero, P Bosch
The development of efficient transfection protocols for livestock cells is crucial for implementation of cell-based transgenic methods to produce genetically modified animals. We synthetized fully deacylated linear 22, 87 and 217 kDa polyethylenimine (PEI) nanoparticles and compared their transfection efficiency and cytotoxicity to commercial branched 25 kDa PEI and linear 58 kDa poly(allylamine) hydrochloride. We studied the effect of PEI size and presence of serum on transfection efficiency on primary cultures of bovine fetal fibroblasts and established cells lines (HEK 293 and Hep G2)...
March 20, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28319150/high-throughput-transformation-of-saccharomyces-cerevisiae-using-liquid-handling-robots
#9
Guangbo Liu, Clayton Lanham, J Ross Buchan, Matthew E Kaplan
Saccharomyces cerevisiae (budding yeast) is a powerful eukaryotic model organism ideally suited to high-throughput genetic analyses, which time and again has yielded insights that further our understanding of cell biology processes conserved in humans. Lithium Acetate (LiAc) transformation of yeast with DNA for the purposes of exogenous protein expression (e.g., plasmids) or genome mutation (e.g., gene mutation, deletion, epitope tagging) is a useful and long established method. However, a reliable and optimized high throughput transformation protocol that runs almost no risk of human error has not been described in the literature...
2017: PloS One
https://www.readbyqxmd.com/read/28319113/combinatorial-crispr-cas9-screens-for-de-novo-mapping-of-genetic-interactions
#10
John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih-Chung Kuo, Dan Du, Assen Roguev, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies...
March 20, 2017: Nature Methods
https://www.readbyqxmd.com/read/28319085/synergistic-drug-combinations-for-cancer-identified-in-a-crispr-screen-for-pairwise-genetic-interactions
#11
Kyuho Han, Edwin E Jeng, Gaelen T Hess, David W Morgens, Amy Li, Michael C Bassik
Identification of effective combination therapies is critical to address the emergence of drug-resistant cancers, but direct screening of all possible drug combinations is infeasible. Here we introduce a CRISPR-based double knockout (CDKO) system that improves the efficiency of combinatorial genetic screening using an effective strategy for cloning and sequencing paired single guide RNA (sgRNA) libraries and a robust statistical scoring method for calculating genetic interactions (GIs) from CRISPR-deleted gene pairs...
March 20, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28315412/engineering-bacterial-translation-initiation-do-we-have-all-the-tools-we-need
#12
REVIEW
Justin Vigar, Hans-Joachim Wieden
BACKGROUND: Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314065/construction-safety-risk-modeling-and-simulation
#13
Antoine J-P Tixier, Matthew R Hallowell, Balaji Rajagopalan
By building on a genetic-inspired attribute-based conceptual framework for safety risk analysis, we propose a novel approach to define, model, and simulate univariate and bivariate construction safety risk at the situational level. Our fully data-driven techniques provide construction practitioners and academicians with an easy and automated way of getting valuable empirical insights from attribute-based data extracted from unstructured textual injury reports. By applying our methodology on a data set of 814 injury reports, we first show the frequency-magnitude distribution of construction safety risk to be very similar to that of many natural phenomena such as precipitation or earthquakes...
March 17, 2017: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/28303954/suppression-of-sin3a-activity-promotes-differentiation-of-pluripotent-cells-into-functional-neurons
#14
Debasish Halder, Chang-Hee Lee, Ji Young Hyun, Gyeong-Eon Chang, Eunji Cheong, Injae Shin
Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303150/development-of-synebrick-vectors-as-a-synthetic-biology-platform-for-gene-expression-in-synechococcus-elongatus-pcc-7942
#15
Wook Jin Kim, Sun-Mi Lee, Youngsoon Um, Sang Jun Sim, Han Min Woo
Cyanobacteria are oxygenic photosynthetic prokaryotes that are able to assimilate CO2 using solar energy and water. Metabolic engineering of cyanobacteria has suggested the possibility of direct CO2 conversion to value-added chemicals. However, engineering of cyanobacteria has been limited due to the lack of various genetic tools for expression and control of multiple genes to reconstruct metabolic pathways for biochemicals from CO2. Thus, we developed SyneBrick vectors as a synthetic biology platform for gene expression in Synechococcus elongatus PCC 7942 as a model cyanobacterium...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28302823/parp-inhibitors-synthetic-lethality-in-the-clinic
#16
REVIEW
Christopher J Lord, Alan Ashworth
PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease...
March 17, 2017: Science
https://www.readbyqxmd.com/read/28299699/synthetic-cell-based-sensors-with-programmed-selectivity-and-sensitivity
#17
Elvis Bernard, Baojun Wang
Bacteria live in an ever changing environment and, to adapt their physiology, they have to sense the changes. Our current understanding of the mechanisms and elements involved in the detection and processing of these environmental signals grant us access to an array of genetic components able to process such information. As engineers can use different electronic components to build a circuit, we can rewire the cellular components to create digital logic and analogue gene circuits that will program cell behaviour in a designed manner in response to a specific stimulus...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28297929/flexible-dynamics-of-two-quorum-sensing-coupled-repressilators
#18
Edward H Hellen, Evgeny Volkov
Genetic oscillators play important roles in cell life regulation. The regulatory efficiency usually depends strongly on the emergence of stable collective dynamic modes, which requires designing the interactions between genetic networks. We investigate the dynamics of two identical synthetic genetic repressilators coupled by an additional plasmid which implements quorum sensing (QS) in each network thereby supporting global coupling. In a basic genetic ring oscillator network in which three genes inhibit each other in unidirectional manner, QS stimulates the transcriptional activity of chosen genes providing for competition between inhibitory and stimulatory activities localized in those genes...
February 2017: Physical Review. E
https://www.readbyqxmd.com/read/28297714/root-microbiota-drive-direct-integration-of-phosphate-stress-and-immunity
#19
Gabriel Castrillo, Paulo José Pereira Lima Teixeira, Sur Herrera Paredes, Theresa F Law, Laura de Lorenzo, Meghan E Feltcher, Omri M Finkel, Natalie W Breakfield, Piotr Mieczkowski, Corbin D Jones, Javier Paz-Ares, Jeffery L Dangl
Plants live in biogeochemically diverse soils with diverse microbiota. Plant organs associate intimately with a subset of these microbes, and the structure of the microbial community can be altered by soil nutrient content. Plant-associated microbes can compete with the plant and with each other for nutrients, but may also carry traits that increase the productivity of the plant. It is unknown how the plant immune system coordinates microbial recognition with nutritional cues during microbiome assembly. Here we establish that a genetic network controlling the phosphate stress response influences the structure of the root microbiome community, even under non-stress phosphate conditions...
March 23, 2017: Nature
https://www.readbyqxmd.com/read/28296915/genetic-variation-in-the-vitamin-d-pathway-cyp2r1-gene-predicts-sustained-hbeag-seroconversion-in-chronic-hepatitis-b-patients-treated-with-pegylated-interferon-a-multicenter-study
#20
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjareon, Tawesak Tanwandee, Phunchai Charatcharoenwitthaya, Satawat Thongsawat, Apinya Leerapun, Teerha Piratvisuth, Rattana Boonsirichan, Chalermrat Bunchorntavakul, Chaowalit Pattanasirigool, Bubpha Pornthisarn, Supot Tantipanichtheerakul, Ekawee Sripariwuth, Woramon Jeamsripong, Teeranan Sanpajit, Yong Poovorawan, Piyawat Komolmit
Evidence of a role of vitamin D in the immune system is increasing. Low serum vitamin D is associated with increased hepatitis B virus replication. Genome-wide association study (GWAS) data has revealed a number of the single nucleotide polymorphisms (SNPs) within the vitamin D synthetic pathway that affect vitamin D functions. We aimed to determine the association between SNPs in the vitamin D gene cascade and response to pegylated interferon (PegIFN) therapy in hepatitis B e-antigen (HBeAg)-positive patients...
2017: PloS One
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