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"Essential gene

Scot P Ouellette
Chlamydia is an obligate intracellular bacterium and, as such, has significantly reduced its genome size and content. Although recent advances have allowed for transformation of C. trachomatis with an exogenous plasmid, genetic manipulation of Chlamydia remains challenging. In particular, the ability to create conditional knockouts has not been developed. This is particularly important given the likelihood that most genes within the small genome of Chlamydia may be essential. Here, I describe the feasibility of using CRISPR interference (CRISPRi) based on the catalytically inactive Cas9 variant (dCas9) of Staphylococcus aureus to inducibly, and reversibly, repress gene expression in C...
2018: Frontiers in Cellular and Infection Microbiology
Xuejin Zhang, Chi Yong Kim, Tori Worthen, William H Witola
Cryptosporidium is a highly prevalent protozoan parasite that is the second leading cause of childhood morbidity and mortality due to diarrhea in developing countries, and causes a serious diarrheal syndrome in calves, lambs and goat kids worldwide. Development of fully effective drugs against Cryptosporidium has mainly been hindered by the lack of genetic tools for functional characterization and validation of potential molecular drug targets in the parasite. Herein, we report the development of a morpholino-based in vivo approach for Cryptosporidium parvum gene knockdown to facilitate determination of the physiological roles of the parasite's genes in a murine model...
March 9, 2018: International Journal for Parasitology
Frank Curmi, Ruben J Cauchi
Gemin3, also known as DDX20 or DP103, is a DEAD-box RNA helicase which is involved in more than one cellular process. Though RNA unwinding has been determined in vitro , it is surprisingly not required for all of its activities in cellular metabolism. Gemin3 is an essential gene, present in Amoeba and Metazoa. The highly conserved N-terminus hosts the helicase core, formed of the helicase- and DEAD-domains, which, based on crystal structure determination, have key roles in RNA binding. The C-terminus of Gemin3 is highly divergent between species and serves as the interaction site for several accessory factors that could recruit Gemin3 to its target substrates and/or modulate its function...
March 9, 2018: Biochemical Society Transactions
Samuel T Coradetti, Dominic Pinel, Gina Geiselman, Masakazu Ito, Stephen Mondo, Morgann C Reilly, Ya-Fang Cheng, Stefan Bauer, Igor Grigoriev, John M Gladden, Blake A Simmons, Rachel Brem, Adam P Arkin, Jeffrey M Skerker
The basidiomycete yeast Rhodosporidium toruloides (a.k.a. Rhodotorula toruloides ) accumulates high concentrations of lipids and carotenoids from diverse carbon sources. It has great potential as a model for the cellular biology of lipid droplets and for sustainable chemical production. We developed a method for high-throughput genetics (RB-TDNAseq), using sequence-barcoded Agrobacterium tumefaciens T-DNA insertions. We identified 1337 putative essential genes with low T-DNA insertion rates. We functionally profiled genes required for fatty acid catabolism and lipid accumulation, validating results with 35 targeted deletion strains...
March 9, 2018: ELife
Stuart J Grice, James N Sleigh, M Zameel Cader
Dominant mutations in GARS , encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D). This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ)...
2018: Frontiers in Molecular Neuroscience
Moritz Horn, Virginia Kroef, Kira Allmeroth, Nicole Schuller, Stephan Miethe, Martin Peifer, Josef M Penninger, Ulrich Elling, Martin S Denzel
Forward genetic screens in haploid mammalian cells have recently emerged as powerful tools for the discovery and investigation of recessive traits. Use of the haploid system provides unique genetic tractability and resolution. Upon positive selection, these screens typically employ analysis of loss-of-function (LOF) alleles and are thus limited to non-essential genes. Many relevant compounds, including anti-cancer therapeutics, however, target essential genes, precluding positive selection of LOF alleles. Here, we asked whether the use of random and saturating chemical mutagenesis might enable screens that identify essential biological targets of toxic compounds...
February 9, 2018: Oncotarget
Michelle L Stoller, Orvelin Roman, Michael R Deans
The organization of polarized stereociliary bundles is critical for the function of the inner ear sensory receptor hair cells that detect sound and motion, and these cells present a striking example of Planar Cell Polarity (PCP); the coordinated orientation of polarized structures within the plane of an epithelium. PCP is best understood in Drosophila where the essential genes regulating PCP were first discovered, and functions for the core PCP proteins encoded by these genes have been deciphered through phenotypic analysis of core PCP gene mutants...
March 3, 2018: Developmental Biology
Bruce L Geller, Lixin Li, Fabian Martinez, Erin Sully, Carolyn R Sturge, Seth M Daly, Christine Pybus, David E Greenberg
Background: Klebsiella pneumoniae is an opportunistic pathogen and many strains are multidrug resistant. KPC is one of the most problematic resistance mechanisms, as it confers resistance to most β-lactams, including carbapenems. A promising platform technology for treating infections caused by MDR pathogens is the nucleic acid-like synthetic oligomers that silence bacterial gene expression by an antisense mechanism. Objectives: To test a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) in a mouse model of K...
March 1, 2018: Journal of Antimicrobial Chemotherapy
Jie Bi, Amita Sehgal, Julie A Williams, Yu-Feng Wang
Wolbachia are endosymbiotic bacteria present in a wide range of insects. Although their dramatic effects on host reproductive biology have been well studied, the effects of Wolbachia on sleep behavior of insect hosts are not well documented. In this study, we report that Wolbachia infection caused an increase of total sleep time in both male and female Drosophila melanogaster. The increase in sleep was associated with an increase in the number of nighttime sleep bouts or episodes, but not in sleep bout duration...
February 27, 2018: Journal of Insect Physiology
Samuel D Stimple, Ashwin Lahiry, Joseph E Taris, David W Wood, Richard A Lease
RNA biology and RNA engineering are subjects of growing interest due to recent advances in our understanding of the diverse cellular functions of RNAs, including their roles as genetic regulators. The noncoding small RNAs (sRNAs) of bacteria are a fundamental basis of regulatory control that can regulate gene expression via antisense base-pairing to one or more target mRNAs. The sRNAs can be customized to generate a range of mRNA translation rates and stabilities. The sRNAs can be applied as a platform for metabolic engineering, to control expression of genes of interest by following relatively straightforward design rules (Kushwaha et al...
2018: Methods in Molecular Biology
Julia di Iulio, Istvan Bartha, Emily H M Wong, Hung-Chun Yu, Victor Lavrenko, Dongchan Yang, Inkyung Jung, Michael A Hicks, Naisha Shah, Ewen F Kirkness, Martin M Fabani, William H Biggs, Bing Ren, J Craig Venter, Amalio Telenti
Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome. Using new Hi-C experimental data, we describe a strong pattern of coordination over 2 Mb where the most constrained regulatory elements associate with the most essential genes...
February 26, 2018: Nature Genetics
Shimpei Aikawa, Sirilak Baramee, Junjarus Sermsathanaswadi, Phakhinee Thianheng, Chakrit Tachaapaikoon, Ayumi Shikata, Rattiya Waeonukul, Patthra Pason, Khanok Ratanakhanokchai, Akihiko Kosugi
An anaerobic, cellulolytic-xylanolytic bacterium, designated strain A7, was isolated from a cellulose-degrading bacterial community inhabiting bovine manure compost on Ishigaki Island, Japan, by enrichment culture using unpretreated corn stover as the sole carbon source. The strain was Gram-positive, non-endospore forming, non-motile, and formed orange colonies on solid medium. Strain A7 was identified as Herbivorax saccincola by DNA-DNA hybridization, and phylogenetic analysis based on 16S rRNA gene sequences showed that it was closely related to H...
February 11, 2018: Systematic and Applied Microbiology
Que Chen, Jeroen B van der Steen, Jos C Arents, Aloysius F Hartog, Srividya Ganapathy, Willem J de Grip, Klaas J Hellingwerf
In many pro- and eukaryotes, a retinal-based proton pump equips the cell to drive ATP synthesis with (sun)light. Such pumps, therefore, have been proposed as a plug-in for cyanobacteria, to artificially increase the efficiency of oxygenic photosynthesis. However, little information on metabolism of retinal, their chromophore, is available for these organisms. We have studied the in vivo role of five genes ( sll1541 ; slr1648 ; slr0091 ; slr1192 ; slr0574 ) potentially involved in retinal metabolism in Synechocystis sp...
February 23, 2018: Applied and Environmental Microbiology
Bingyin Peng, Lars K Nielsen, Sotirios C Kampranis, Claudia E Vickers
Monoterpene production in Saccharomyces cerevisae requires the introduction of heterologous monoterpene synthases (MTSs). The endogenous farnesyl pyrosphosphate synthase (FPPS; Erg20p) competes with MTSs for the precursor geranyl pyrophosphate (GPP), which limits the production of monoterpenes. ERG20 is an essential gene that cannot be deleted and transcriptional down-regulation of ERG20 has failed to improve monoterpene production. Here, we investigated an N-degron-dependent protein degradation strategy to down-regulate Erg20p activity...
February 19, 2018: Metabolic Engineering
Bashir Sajo Mienda, Rabiu Salihu, Aliyu Adamu, Shehu Idris
The growing number of multidrug-resistant pathogenic bacteria is becoming a world leading challenge for the scientific community and for public health. However, advances in high-throughput technologies and whole-genome sequencing of bacterial pathogens make the construction of bacterial genome-scale metabolic models (GEMs) increasingly realistic. The use of GEMs as an alternative platforms will expedite identification of novel unconditionally essential genes and enzymes of target organisms with existing and forthcoming GEMs...
February 22, 2018: Future Microbiology
Peter Rugbjerg, Kira Sarup-Lytzen, Mariann Nagy, Morten Otto Alexander Sommer
Bio-production of chemicals is an important driver of the societal transition toward sustainability. However, fermentations with heavily engineered production organisms can be challenging to scale to industrial volumes. Such fermentations are subject to evolutionary pressures that select for a wide range of genetic variants that disrupt the biosynthetic capacity of the engineered organism. Synthetic product addiction that couples high-yield production of a desired metabolite to expression of nonconditionally essential genes could offer a solution to this problem by selectively favoring cells with biosynthetic capacity in the population without constraining the medium...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Emily C A Goodall, Ashley Robinson, Iain G Johnston, Sara Jabbari, Keith A Turner, Adam F Cunningham, Peter A Lund, Jeffrey A Cole, Ian R Henderson
Transposon-directed insertion site sequencing (TraDIS) is a high-throughput method coupling transposon mutagenesis with short-fragment DNA sequencing. It is commonly used to identify essential genes. Single gene deletion libraries are considered the gold standard for identifying essential genes. Currently, the TraDIS method has not been benchmarked against such libraries, and therefore, it remains unclear whether the two methodologies are comparable. To address this, a high-density transposon library was constructed in Escherichia coli K-12...
February 20, 2018: MBio
Mohammad HamediRad, Jiazhang Lian, Hejun Li, Huimin Zhao
Xylose is a major component of lignocellulosic biomass, one of the most abundant feedstocks for biofuel production. Therefore, efficient and rapid conversion of xylose to ethanol is crucial in the viability of lignocellulosic biofuel plants. In this study, RNAi Assisted Genome Evolution (RAGE) was used to improve the xylose utilization rate in SR8, one of the most efficient publicly available xylose utilizing Saccharomyces cerevisiae strains. To identify gene targets for further improvement, we created a genome-scale library consisting of both genetic over-expression and down-regulation mutations in SR8...
February 20, 2018: Biotechnology and Bioengineering
Drew S Tack, Austin C Cole, Raghav Shroff, Barrett R Morrow, Andrew D Ellington
Since the fixation of the genetic code, evolution has largely been confined to 20 proteinogenic amino acids. The development of orthogonal translation systems that allow for the codon-specific incorporation of noncanonical amino acids may provide a means to expand the code, but these translation systems cannot be simply superimposed on cells that have spent billions of years optimizing their genomes with the canonical code. We have therefore carried out directed evolution experiments with an orthogonal translation system that inserts 3-nitro-L-tyrosine across from amber codons, creating a 21 amino acid genetic code in which the amber stop codon ambiguously encodes either 3-nitro-L-tyrosine or stop...
February 19, 2018: Scientific Reports
Jun Lin, Yiming Liu, Hao Wu, Zhihai Huang, Jingfan Ma, Chang Guo, Feng Gao, Peipei Jin, Pengfei Wei, Yunjiao Zhang, Liu Liu, Rui Zhang, Longxin Qiu, Ning Gu, Longping Wen
Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a well-established mechanism involving dephosphorylation of TFEB at serine-142 and serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus translocation precedes autophagy induced by Ag NPs and leads to enhanced expression of autophagy-essential genes...
February 19, 2018: Small
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