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Nature Biotechnology

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https://www.readbyqxmd.com/read/28628130/lipid-production-in-nannochloropsis-gaditana-is-doubled-by-decreasing-expression-of-a-single-transcriptional-regulator
#1
Imad Ajjawi, John Verruto, Moena Aqui, Leah B Soriaga, Jennifer Coppersmith, Kathleen Kwok, Luke Peach, Elizabeth Orchard, Ryan Kalb, Weidong Xu, Tom J Carlson, Kristie Francis, Katie Konigsfeld, Judit Bartalis, Andrew Schultz, William Lambert, Ariel S Schwartz, Robert Brown, Eric R Moellering
Lipid production in the industrial microalga Nannochloropsis gaditana exceeds that of model algal species and can be maximized by nutrient starvation in batch culture. However, starvation halts growth, thereby decreasing productivity. Efforts to engineer N. gaditana strains that can accumulate biomass and overproduce lipids have previously met with little success. We identified 20 transcription factors as putative negative regulators of lipid production by using RNA-seq analysis of N. gaditana during nitrogen deprivation...
June 19, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28604661/computational-design-of-trimeric-influenza-neutralizing-proteins-targeting-the-hemagglutinin-receptor-binding-site
#2
Eva-Maria Strauch, Steffen M Bernard, David La, Alan J Bohn, Peter S Lee, Caitlin E Anderson, Travis Nieusma, Carly A Holstein, Natalie K Garcia, Kathryn A Hooper, Rashmi Ravichandran, Jorgen W Nelson, William Sheffler, Jesse D Bloom, Kelly K Lee, Andrew B Ward, Paul Yager, Deborah H Fuller, Ian A Wilson, David Baker
Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites...
June 12, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28604660/1-003-reference-genomes-of-bacterial-and-archaeal-isolates-expand-coverage-of-the-tree-of-life
#3
Supratim Mukherjee, Rekha Seshadri, Neha J Varghese, Emiley A Eloe-Fadrosh, Jan P Meier-Kolthoff, Markus Göker, R Cameron Coates, Michalis Hadjithomas, Georgios A Pavlopoulos, David Paez-Espino, Yasuo Yoshikuni, Axel Visel, William B Whitman, George M Garrity, Jonathan A Eisen, Philip Hugenholtz, Amrita Pati, Natalia N Ivanova, Tanja Woyke, Hans-Peter Klenk, Nikos C Kyrpides
We present 1,003 reference genomes that were sequenced as part of the Genomic Encyclopedia of Bacteria and Archaea (GEBA) initiative, selected to maximize sequence coverage of phylogenetic space. These genomes double the number of existing type strains and expand their overall phylogenetic diversity by 25%. Comparative analyses with previously available finished and draft genomes reveal a 10.5% increase in novel protein families as a function of phylogenetic diversity. The GEBA genomes recruit 25 million previously unassigned metagenomic proteins from 4,650 samples, improving their phylogenetic and functional interpretation...
June 12, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28604659/inference-and-quantification-of-peptidoforms-in-large-sample-cohorts-by-swath-ms
#4
George Rosenberger, Yansheng Liu, Hannes L Röst, Christina Ludwig, Alfonso Buil, Ariel Bensimon, Martin Soste, Tim D Spector, Emmanouil T Dermitzakis, Ben C Collins, Lars Malmström, Ruedi Aebersold
Consistent detection and quantification of protein post-translational modifications (PTMs) across sample cohorts is a prerequisite for functional analysis of biological processes. Data-independent acquisition (DIA) is a bottom-up mass spectrometry approach that provides complete information on precursor and fragment ions. However, owing to the convoluted structure of DIA data sets, confident, systematic identification and quantification of peptidoforms has remained challenging. Here, we present inference of peptidoforms (IPF), a fully automated algorithm that uses spectral libraries to query, validate and quantify peptidoforms in DIA data sets...
June 12, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28581492/engineered-cpf1-variants-with-altered-pam-specificities
#5
Linyi Gao, David B T Cox, Winston X Yan, John C Manteiga, Martin W Schneider, Takashi Yamano, Hiroshi Nishimasu, Osamu Nureki, Nicola Crosetto, Feng Zhang
The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells...
June 5, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28562594/guided-self-organization-and-cortical-plate-formation-in-human-brain-organoids
#6
Madeline A Lancaster, Nina S Corsini, Simone Wolfinger, E Hilary Gustafson, Alex W Phillips, Thomas R Burkard, Tomoki Otani, Frederick J Livesey, Juergen A Knoblich
Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies...
May 31, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28553942/digital-to-biological-converter-for-on-demand-production-of-biologics
#7
Kent S Boles, Krishna Kannan, John Gill, Martina Felderman, Heather Gouvis, Bolyn Hubby, Kurt I Kamrud, J Craig Venter, Daniel G Gibson
Manufacturing processes for biological molecules in the research laboratory have failed to keep pace with the rapid advances in automization and parellelization. We report the development of a digital-to-biological converter for fully automated, versatile and demand-based production of functional biologics starting from DNA sequence information. Specifically, DNA templates, RNA molecules, proteins and viral particles were produced in an automated fashion from digitally transmitted DNA sequences without human intervention...
May 29, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28553941/engineered-bacteria-can-function-in-the-mammalian-gut-long-term-as-live-diagnostics-of-inflammation
#8
David T Riglar, Tobias W Giessen, Michael Baym, S Jordan Kerns, Matthew J Niederhuber, Roderick T Bronson, Jonathan W Kotula, Georg K Gerber, Jeffrey C Way, Pamela A Silver
Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut but commercial translation of technologies to accomplish this has been hindered by the susceptibility of synthetic genetic circuits to mutation and unpredictable function during extended gut colonization. Here, we report stable, engineered bacterial strains that maintain their function for 6 months in the mouse gut. We engineered a commensal murine Escherichia coli strain to detect tetrathionate, which is produced during inflammation...
May 29, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28553940/single-cell-genome-sequencing-at-ultra-high-throughput-with-microfluidic-droplet-barcoding
#9
Freeman Lan, Benjamin Demaree, Noorsher Ahmed, Adam R Abate
The application of single-cell genome sequencing to large cell populations has been hindered by technical challenges in isolating single cells during genome preparation. Here we present single-cell genomic sequencing (SiC-seq), which uses droplet microfluidics to isolate, fragment, and barcode the genomes of single cells, followed by Illumina sequencing of pooled DNA. We demonstrate ultra-high-throughput sequencing of >50,000 cells per run in a synthetic community of Gram-negative and Gram-positive bacteria and fungi...
May 29, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#10
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28504667/rapid-cloning-of-genes-in-hexaploid-wheat-using-cultivar-specific-long-range-chromosome-assembly
#11
Anupriya Kaur Thind, Thomas Wicker, Hana Šimková, Dario Fossati, Odile Moullet, Cécile Brabant, Jan Vrána, Jaroslav Doležel, Simon G Krattinger
Cereal crops such as wheat and maize have large repeat-rich genomes that make cloning of individual genes challenging. Moreover, gene order and gene sequences often differ substantially between cultivars of the same crop species. A major bottleneck for gene cloning in cereals is the generation of high-quality sequence information from a cultivar of interest. In order to accelerate gene cloning from any cropping line, we report 'targeted chromosome-based cloning via long-range assembly' (TACCA). TACCA combines lossless genome-complexity reduction via chromosome flow sorting with Chicago long-range linkage to assemble complex genomes...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591128/after-glybera-s-withdrawal-what-s-next-for-gene-therapy
#12
Melanie Senior
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591127/eat-a-water-bottle-or-two
#13
(no author information available yet)
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591126/around-the-world-in-a-month
#14
(no author information available yet)
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591125/open-source-community-driven-microfluidics-with-metafluidics
#15
David S Kong, Todd A Thorsen, Jonathan Babb, Scott T Wick, Jeremy J Gam, Ron Weiss, Peter A Carr
Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. We present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device...
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591124/patient-centered-drug-manufacture
#16
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591123/building-the-human-inner-ear-in-an-organoid
#17
Vidhya Munnamalai, Donna M Fekete
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591122/car-t-death-strikes-kite
#18
(no author information available yet)
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591121/a-spring-collection-of-designer-yeast-chromosomes
#19
Katarzyna Marcinkiewicz
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28591119/manufacture-of-car-t-cells-in-the-body
#20
Johanna Olweus
No abstract text is available yet for this article.
June 7, 2017: Nature Biotechnology
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