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Synthetic genetics

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https://www.readbyqxmd.com/read/28432094/the-use-of-synthetic-hybrid-strains-to-determine-the-role-of-replicon-3-in-virulence-of-the-burkholderia-cepacia-complex
#1
Kirsty Agnoli, Roman Freitag, Margarida C Gomes, Christian Jenul, Angela Suppiger, Olga Mannweiler, Carmen Frauenknecht, Daniel Janser, Annette C Vergunst, Leo Eberl
The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity with great biotechnological potential, but the utilisation of these bacteria is limited by their opportunistic pathogenicity to humans. The third replicon of the Bcc, megaplasmid pC3 (0.5 to 1.4 Mb, previously chromosome 3), is important for various phenotypes, including virulence, antifungal and proteolytic activities, and the utilization of certain substrates. Approximately half of plasmid pC3 is well-conserved throughout sequenced Bcc members, while the other half is not...
April 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28431252/engineered-regulatory-systems-modulate-gene-expression-of-human-commensals-in-the-gut
#2
Bentley Lim, Michael Zimmermann, Natasha A Barry, Andrew L Goodman
The gut microbiota is implicated in numerous aspects of health and disease, but dissecting these connections is challenging because genetic tools for gut anaerobes are limited. Inducible promoters are particularly valuable tools because these platforms allow real-time analysis of the contribution of microbiome gene products to community assembly, host physiology, and disease. We developed a panel of tunable expression platforms for the prominent genus Bacteroides in which gene expression is controlled by a synthetic inducer...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430194/engineering-genetic-circuit-interactions-within-and-between-synthetic-minimal-cells
#3
Katarzyna P Adamala, Daniel A Martin-Alarcon, Katriona R Guthrie-Honea, Edward S Boyden
Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28430101/synthetic-temperature-inducible-lethal-gene-circuits-in-escherichia-coli
#4
Stephanie C Pearce, Ralph L McWhinnie, Francis E Nano
Temperature sensitivity is often used as a way to attenuate micro-organisms to convert them into live vaccines. In this work, we explore the use of temperature-sensitive (TS) genetic circuits that express lethal genes as a widely applicable approach to TS attenuation. We tested different combinations of TS repressors and cognate promoters controlling the expression of genes encoding restriction endonucleases inserted at four different non-essential sites in the Escherichia coli chromosome. We found that the presence of the restriction endonuclease genes did not affect the viability of the host strains at the permissive temperature, but that expression of the genes at elevated temperatures killed the strains to varying extents...
April 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28429326/wax-ester-fermentation-and-its-application-for-biofuel-production
#5
Hiroshi Inui, Takahiro Ishikawa, Masahiro Tamoi
In Euglena cells under anaerobic conditions, paramylon, the storage polysaccharide, is promptly degraded and converted to wax esters. The wax esters synthesized are composed of saturated fatty acids and alcohols with chain lengths of 10-18, and the major constituents are myristic acid and myristyl alcohol. Since the anaerobic cells gain ATP through the conversion of paramylon to wax esters, the phenomenon is named "wax ester fermentation". The wax ester fermentation is quite unique in that the end products, i...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28428873/a-maize-landrace-that-emits-defense-volatiles-in-response-to%C3%A2-herbivore-eggs-possesses-a-strongly-inducible-terpene-synthase-gene
#6
Amanuel Tamiru, Toby J A Bruce, Annett Richter, Christine M Woodcock, Charles A O Midega, Jörg Degenhardt, Segenet Kelemu, John A Pickett, Zeyaur R Khan
Maize (Zea mays) emits volatile terpenes in response to insect feeding and egg deposition to defend itself against harmful pests. However, maize cultivars differ strongly in their ability to produce the defense signal. To further understand the agroecological role and underlying genetic mechanisms for variation in terpene emission among maize cultivars, we studied the production of an important signaling component (E)-caryophyllene in a South American maize landrace Braz1006 possessing stemborer Chilo partellus egg inducible defense trait, in comparison with the European maize line Delprim and North American inbred line B73...
April 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28428056/recent-development-of-synthetic-nonviral-systems-for-sustained-gene-delivery
#7
REVIEW
Yonggang Xiang, Nwe Nwe Linn Oo, Jin Ping Lee, Zibiao Li, Xian Jun Loh
Sustained gene delivery is of particular importance today because it circumvents the need for repeated therapeutic administration and provides spatial and temporal control of the release profile. Better understanding of the genetic basis of diseases and advances in gene therapy have propelled significant research on biocompatible gene carriers for therapeutic purposes. Varied biodegradable polymer-based architectures have been used to create new compositions with unique properties suitable for sustained gene delivery...
April 17, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28426952/plant-viruses-and-bacteriophages-for-delivery-in-medicine-and-biotechnology
#8
REVIEW
Anna E Czapar, Nicole F Steinmetz
There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals...
April 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28426191/genome-wide-abolishment-of-mobile-genetic-elements-using-genome-shuffling-and-crispr-cas-assisted-mage-allows-the-efficient-stabilization-of-a-bacterial-chassis
#9
Kinga Umenhoffer, Gábor Draskovits, Ákos Nyerges, Ildikó Karcagi, Balázs Bogos, Edit Tímár, Bálint Csörgő, Róbert Herczeg, István Nagy, Tamás Fehér, Csaba Pal, Gyorgy Posfai
The ideal bacterial chassis provides a simplified, stable and predictable host environment for synthetic biological circuits. Mutability and evolution can, however, compromise stability, leading to deterioration of artificial genetic constructs. By eliminating certain sources of instability, these undesired genetic changes can be mitigated. Specifically, deletion of prophages and insertion sequences, non-essential constituents of bacterial genomes, has been shown to be beneficial in cellular and genetic stabilization...
April 20, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28423456/progesterone-resistance-in-endometriosis-origins-consequences-and-interventions
#10
Bansari G Patel, Martin Rudnicki, Jie Yu, Yimin Shu, Robert N Taylor
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis...
April 19, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28421372/vascular-development-of-the-grapevine-vitis-vinifera-l-inflorescence-rachis-in-response-to-flower-number-plant-growth-regulators-and-defoliation
#11
Aude M Gourieroux, Bruno P Holzapfel, Margaret E McCully, Geoffrey R Scollary, Suzy Y Rogiers
The grapevine inflorescence is a determinate panicle and as buds emerge, shoot, flower and rachis development occur simultaneously. The growth and architecture of the rachis is determined by genetic and environmental factors but here we examined the role of flower and leaf number as well as hormones on its elongation and vascular development. The consequences of rachis morphology and vascular area on berry size and composition were also assessed. One week prior to anthesis, Merlot and Cabernet Sauvignon field vines were exposed to manual flower removal, exogenous plant growth regulators or pre-bloom leaf removal...
April 18, 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/28418644/emma-an-extensible-mammalian-modular-assembly-toolkit-for-the-rapid-design-and-production-of-diverse-expression-vectors
#12
Andrea Martella, Mantas Matjusaitis, Jamie Auxillos, Steven Michael Pollard, Yizhi Cai
Mammalian plasmid expression vectors are critical reagents underpinning many facets of research across biology, biomedical research, and the biotechnology industry. Traditional cloning methods often require laborious manual design and assembly of plasmids using tailored sequential cloning steps. This process can be protracted, complicated, expensive and error-prone. New tools and strategies that facilitate the efficient design and production of bespoke vectors would help relieve a current bottleneck for researchers...
April 18, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28415985/vitamin-d-related-gene-polymorphism-predict-treatment-response-to-pegylated-interferon-based-therapy-in-thai-chronic-hepatitis-c-patients
#13
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjaroen, Pisit Tangkijvanich, Sombat Treeprasertsuk, Panarat Thaimai, Rujipat Wasitthankasem, Yong Poovorawan, Piyawat Komolmit
BACKGROUND: Patients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. METHODS: The study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin...
April 17, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28414800/semantic-prioritization-of-novel-causative-genomic-variants
#14
Imane Boudellioua, Rozaimi B Mahamad Razali, Maxat Kulmanov, Yasmeen Hashish, Vladimir B Bajic, Eva Goncalves-Serra, Nadia Schoenmakers, Georgios V Gkoutos, Paul N Schofield, Robert Hoehndorf
Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets...
April 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28414320/inhibition-of-dna2-nuclease-as-a-therapeutic-strategy-targeting-replication-stress-in-cancer-cells
#15
S Kumar, X Peng, J Daley, L Yang, J Shen, N Nguyen, G Bae, H Niu, Y Peng, H-J Hsieh, L Wang, C Rao, C C Stephan, P Sung, G Ira, G Peng
Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity...
April 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28413444/functional-photosystem-i-maintains-proper-energy-balance-during-nitrogen-depletion-in-chlamydomonas-reinhardtii-promoting-triacylglycerol-accumulation
#16
Mahmoud Gargouri, Philip D Bates, Jeong-Jin Park, Helmut Kirchhoff, David R Gang
BACKGROUND: Nutrient deprivation causes significant stress to the unicellular microalga, Chlamydomonas reinhardtii, which responds by significantly altering its metabolic program. Following N deprivation, the accumulation of starch and triacylglycerols (TAGs) is significantly altered following massive reprogramming of cellular metabolism. One protein that was found to change dramatically and early to this stress was TAB2, a photosystem I (PSI) translation initiation factor, whose transcript and protein levels increased significantly after only 30 min of N deprivation...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28410475/exploring-the-potential-of-saccharomyces-cerevisiae-for-biopharmaceutical-protein-production
#17
REVIEW
Guokun Wang, Mingtao Huang, Jens Nielsen
Production of recombinant proteins by yeast plays a vital role in the biopharmaceutical industry. It is therefore desirable to develop yeast platform strains for over-production of various biopharmaceutical proteins, but this requires fundamental knowledge of the cellular machinery, especially the protein secretory pathway. Integrated analyses of multi-omics datasets can provide comprehensive understanding of cellular function, and can enable systems biology-driven and mathematical model-guided strain engineering...
April 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28406948/quicklib-a-method-for-building-fully-synthetic-plasmid-libraries-by-seamless-cloning-of-degenerate-oligonucleotides
#18
Pierre Galka, Elisabeth Jamez, Gilles Joachim, Patrice Soumillion
Incorporation of synthetic degenerate oligonucleotides into plasmids for building highly diverse genetic libraries requires efficient and quantitative DNA manipulation. We present a fast and seamless method for generating libraries of PCR-synthesized plasmids designed with a degenerate sequence and short overlapping ends. Our method called QuickLib should find many applications in synthetic biology; as an example, we easily prepared genetic libraries of Escherichia coli expressing billions of different backbone cyclic peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28403011/emerging-roles-of-lipid-metabolism-in-cancer-progression
#19
Cyril Corbet, Olivier Feron
PURPOSE OF REVIEW: Lipid metabolism in cancer cells and tumor-associated stromal cells was recently identified to contribute to disease progression particularly in response to changes in tumor microenvironment such as acidosis and hypoxia. RECENT FINDINGS: New molecular mechanisms driving lipid metabolism in various cancers were elicited through genetic silencing, pharmacological inhibition of key metabolic enzymes, including those involved in fatty acid oxidation and synthesis, and modulation of diet composition...
April 11, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28398839/foundational-and-translational-research-opportunities-to-improve-plant-health
#20
Richard W Michelmore, Gitta Coaker, Rebecca Bart, Gwyn A Beattie, Andrew Bent, Toby Bruce, Duncan Cameron, Jeff Dangl, Savithramma Dinesh-Kumar, Robert Edwards, Sebastian Eves-van den Akker, Walter Gassmann, Jean Greenberg, Richard Harrison, Ping He, Jagger Harvey, Alisa Huffaker, Scot Hulbert, Roger Innes, Jonathan D Jones, Isgouhi Kaloshian, Sophien Kamoun, Fumiaki Katagiri, Jan E Leach, Wenbo Ma, John M McDowell, June Medford, Blake Meyers, Rebecca Nelson, Richard Peter Oliver, Yiping Qi, Diane Saunders, Michael Shaw, Prasanta Subudhi, Leslie Torrance, Brett M Tyler, John Walsh
This whitepaper reports the deliberations of a workshop focused on biotic challenges to plant health held in Washington, D.C. in September 2016. Ensuring health of food plants is critical to maintaining the quality and productivity of crops and for sustenance of the rapidly growing human population. There is a close linkage between food security and societal stability; however, global food security is threatened by the vulnerability of our agricultural systems to numerous pests, pathogens, weeds, and environmental stresses...
April 11, 2017: Molecular Plant-microbe Interactions: MPMI
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