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Synthetic genetics

Xingchen Zhou, Wu Zhu, Minxue Shen, Yijing He, Cong Peng, Yehong Kuang, Juan Su, Shuang Zhao, Xiang Chen, Wangqing Chen
Background: Acitretin is a second-generation synthetic retinoid, and is widely used for treating the severe psoriasis vulgaris. However, it should be chosen with caution for its cardiovascular risk, and it is reported that acitretin may increase the serum lipids. The purpose of this study is to investigate the relationship between the Frizzled-related proteins 4 (SFRP4) rs1802073 polymorphism and the changes of serum lipids in Chinese psoriatic patients during the treatment with acitretin...
2018: PeerJ
Ifat Sher, Adi Tzameret, Sara Peri-Chen, Victoria Edelshtain, Michael Ioffe, Alon Sayer, Ludmila Buzhansky, Ehud Gazit, Ygal Rotenstreich
The retinoid cycle enzymes regenerate the visual chromophore 11-cis retinal to enable vision. Mutations in the genes encoding the proteins of the retinoid cycle are the leading cause for recessively inherited retinal dystrophies such as retinitis pigmentosa, Leber congenital amaurosis, congenital cone-rod dystrophy and fundus albipunctatus. Currently there is no treatment for these blinding diseases. In previous studies we demonstrated that oral treatment with the 9-cis-β-carotene rich Dunaliella Bardawil algae powder significantly improved visual and retinal functions in patients with retinitis pigmentosa and fundus albipunctatus...
April 17, 2018: Scientific Reports
Anna Buchman, John M Marshall, Dennis Ostrovski, Ting Yang, Omar S Akbari
Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii We demonstrate that this drive system, based on an engineered maternal "toxin" coupled with a linked embryonic "antidote," is capable of biasing Mendelian inheritance rates with up to 100% efficiency...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
Pia Dosenovic, Ervin E Kara, Anna-Klara Pettersson, Andrew T McGuire, Matthew Gray, Harald Hartweger, Eddy S Thientosapol, Leonidas Stamatatos, Michel C Nussenzweig
The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Martha J Nelson-Flower, Tom P Flower, Amanda R Ridley
Many cooperatively breeding societies are characterized by high reproductive skew, such that some socially dominant individuals breed, while socially subordinate individuals provide help. Inbreeding avoidance serves as a source of reproductive skew in many high-skew societies, but few empirical studies have examined sources of skew operating alongside inbreeding avoidance, or compared individual attempts to reproduce (reproductive competition) with individual reproductive success. Here we use long-term genetic and observational data to examine factors affecting reproductive skew in the high-skew cooperatively breeding southern pied babbler (Turdoides bicolor)...
April 16, 2018: Molecular Ecology
Sambandam Ravikumar, Han Min Woo, Jong-Il Choi
Novel synthetic isoprenoids have been synthesized in engineered microbial hosts by evolving terpene synthase or expressing heterologous terpene synthases. Recently, the native operon, crtN a N c M derived from Planococcus sp. PAMC 21323, has isolated for potential industrial applications of C35 carotenoids. For the first time, novel C35 carotenoids (sesquarterpene) were synthesized in Corynebacterium glutamicum expressing the crtN a N c M genes. The recombinant strains accumulate various sesquarterpene including 4-apolycopene (red color), 4-aponeurosporene (yellow color), and no pigmentation, depending on the expression of the genetic elements of the crtN a N c M genes...
April 17, 2018: Applied Biochemistry and Biotechnology
Cynthia K Holland, Joseph M Jez
Arabidopsis thaliana (thale cress) has a past, current, and future role in the era of synthetic biology. Arabidopsis is one of the most well-studied plants with a wealth of genomics, genetics, and biochemical resources available for the metabolic engineer and synthetic biologist. Here we discuss the tools and resources that enable the identification of target genes and pathways in Arabidopsis and heterologous expression in this model plant. While there are numerous examples of engineering Arabidopsis for decreased lignin, increased seed oil, increased vitamins, and environmental remediation, this plant has provided biochemical tools for introducing Arabidopsis genes, pathways, and/or regulatory elements into other plants and microorganisms...
April 16, 2018: Plant Cell Reports
Siddharth Patel, Avathamsa Athirasala, Paula Dos Passos Menezes, Narayanan Ashwanikumar, Ting Zou, Gaurav Sahay, Luiz Bertassoni
The ability to control cellular processes and precisely direct cellular reprogramming has revolutionized regenerative medicine. Recent advances in in vitro transcribed (IVT) mRNA technology with chemical modifications have led to development of methods that control spatio-temporal gene expression. Additionally, there is a current thrust towards the development of safe, integration-free approaches to gene therapy for translational purposes. In this review, we describe strategies of synthetic IVT mRNA modifications and non-viral technologies for intracellular delivery...
April 17, 2018: Tissue Engineering. Part A
François Bertaux, Samuel Marguerat, Vahid Shahrezaei
The cell division rate, size and gene expression programmes change in response to external conditions. These global changes impact on average concentrations of biomolecule and their variability or noise. Gene expression is inherently stochastic, and noise levels of individual proteins depend on synthesis and degradation rates as well as on cell-cycle dynamics. We have modelled stochastic gene expression inside growing and dividing cells to study the effect of division rates on noise in mRNA and protein expression...
March 2018: Royal Society Open Science
Vojtech Hudzieczek, Radim Cegan, Tomas Cermak, Nela Bacovska, Zuzana Machalkova, Karel Dolezal, Lucie Plihalova, Daniel Voytas, Roman Hobza, Boris Vyskot
Silene latifolia serves as a model species to study dioecy, the evolution of sex chromosomes, dosage compensation and sex-determination systems in plants. Currently, no protocol for genetic transformation is available for this species, mainly because S. latifolia is considered recalcitrant to in vitro regeneration and infection with Agrobacterium tumefaciens. Using cytokinins and their synthetic derivatives, we markedly improved the efficiency of regeneration. Several agrobacterial strains were tested for their ability to deliver DNA into S...
April 12, 2018: New Biotechnology
Martyn Dade-Robertson, Helen Mitrani, Javier Rodriguez Corral, Meng Zhang, Luis Hernan, Aurelie Guyet, Anil Wipat
In this paper, we describe the first steps in the design of a synthetic biological system based on the use of genetically modified bacteria to detect elevated pressures in soils and respond by cementing soil particles. Such a system might, for example, enable a self- constructed foundation to form in response to load using engineered bacteria which could be seeded and grown in the soils. This process would reduce the need for large-scale excavations and may be the basis for a new generation of self-assembling and responsive bio-based materials...
April 13, 2018: Bioinspiration & Biomimetics
Samson Simon, Mathias Otto, Margret Engelhard
No abstract text is available yet for this article.
April 12, 2018: EMBO Reports
Yunhua Liu, Hanchen Xu, Kevin Van der Jeught, Yujing Li, Sheng Liu, Lu Zhang, Yuanzhang Fang, Xinna Zhang, Milan Rodovich, Bryan P Schneider, Xiaoming He, Cheng Huang, Chi Zhang, Jun Wan, Guang Ji, Xiongbin Lu
Synthetic lethality-based strategy has been developed to identify therapeutic targets in cancer harboring tumor suppressor gene mutations, as exemplified by the effectiveness of PARP inhibitors in BRCA1/2-mutated tumors. However, many synthetic lethal interactors are less reliable due to the fact that such genes usually do not perform fundamental or indispensable functions in the cell. Here we developed an approach to identify the "essential lethality" arose from these mutated/deleted essential genes, which are largely tolerated in cancer cells due to genetic redundancy...
April 12, 2018: Journal of Clinical Investigation
Arun Kumar, Trine Sundebo Meldgaard, Sylvie Bertholet
Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses...
2018: Frontiers in Immunology
Roberto Semeraro, Valerio Orlandini, Alberto Magi
The adoption of next generation sequencing based methods in cancer research allowed for the investigation of the complex genetic structure of tumor samples. In the last few years, considerable importance was given to the research of somatic variants and several computational approaches were developed for this purpose. Despite continuous improvements to these programs, the validation of their results it's a hard challenge due to multiple sources of error. To overcome this drawback different simulation approaches are used to generate synthetic samples but they are often based on the addition of artificial mutations that mimic the complexity of genomic variations...
2018: PloS One
Craig J van Dolleweerd, Sarah A Kessans, Kyle C Van de Bittner, Leyla Y Bustamante, Rudranuj Bundela, Barry Scott, Matthew J Nicholson, Emily J Parker
A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements...
April 5, 2018: ACS Synthetic Biology
Vijaya Bharathi Srinivasan, Mahavinod Angrasan, Neha Chandel, Govindan Rajamohan
In this study, we delineated the genome sequence of a Bacillus cereus strain BC04 isolated from a stool sample in India. The draft genome is 5.1 Mb in size and consists of total 109 scaffolds, GC content is 35.2% with 5182 coding genes. The comparative analysis with other completely sequenced genomes highlights the unique presence of genomic islands, hemolysin, capsular synthetic protein, modifying enzymes accC7 and catA15, regulators of antibiotic resistance MarR and LysR with annotated functions related to virulence, stress response, and antimicrobial resistance...
April 4, 2018: Functional & Integrative Genomics
Allen J Roth, Stewart Shuman, Beate Schwer
A seven-subunit Lsm2-8 protein ring assembles on the U-rich 3' end of the U6 snRNA. A structure-guided mutational analysis of the Saccharomyces cerevisiae Lsm2-8 ring affords new insights to structure-function relations and genetic interactions of the Lsm subunits. Alanine scanning of 39 amino acids comprising the RNA-binding sites or inter-subunit interfaces of Lsm2, Lsm3, Lsm4, Lsm5, and Lsm8 identified only one instance of lethality (Lsm3-R69A) and one severe growth defect (Lsm2-R63A), both involving amino acids that bind the 3'-terminal UUU trinucleotide...
April 3, 2018: RNA
Tim Snoek, David Romero-Suarez, Jie Zhang, Francesca Ambri, Mette L Skjoedt, Suresh Sudarsan, Michael K Jensen, Jay D Keasling
Microbes offer enormous potential for production of industrially relevant chemicals and therapeutics, yet the rapid identification of high-producing microbes from large genetic libraries is a major bottleneck in modern cell factory development. Here, we develop and apply a synthetic selection system in Saccharomyces cerevisiae that couples the concentration of muconic acid, a plastic precursor, to cell fitness by using the prokaryotic transcriptional regulator BenM driving an antibiotic resistance gene. We show that the sensor-selector does not affect production nor fitness, and find that tuning pH of the cultivation medium limits the rise of nonproducing cheaters...
April 5, 2018: ACS Synthetic Biology
Ilirjana Bajrami, Rebecca Marlow, Marieke van de Ven, Rachel Brough, Helen N Pemberton, Jessica Frankum, Feifei Song, Rumana Rafiq, Asha Konde, Dragomir B Krastev, Malini Menon, James Campbell, Aditi Gulati, Rahul Kumar, Stephen J Pettitt, Mark D Gurden, Marta Llorca Cardenosa, Irene Chong, Patrycja Gazinska, Fredrik Wallberg, Elinor J Sawyer, Lesley-Ann Martin, Mitch Dowsett, Spiros Linardopoulos, Rachael Natrajan, Colm J Ryan, Patrick W B Derksen, Jos Jonkers, Andrew N J Tutt, Alan Ashworth, Christopher J Lord
The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib...
April 2018: Cancer Discovery
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