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Synthetic genetics

Xue-Jian Zhang, Xiao-Wei Wang, Xiao-Di Da, Yanlin Shi, Chunli Liu, Fei Sun, Shuguang Yang, Wen-Bin Zhang
Protein-based materials call for innovative processing techniques to integrate their unique biologically enabled functions with other materials of complementary features. Herein, we report the covalent protein layer-by-layer assembly via orthogonal "Tag-Catcher" reactions as a facile and robust approach to make entirely protein-based multilayers on a variety of substrates. Programmed assembly of native telechelic proteins not only endows the materials valuable stimuli-sensitive behaviors, but also unique properties unparalleled by any synthetic counterparts...
February 14, 2018: Biomacromolecules
Clare Rusbridge, Francisco J Salguero, Monique Antoinette David, Kiterie M E Faller, Jose T Bras, Rita J Guerreiro, Angela C Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G P Brandner, Brian Summers, John Hardy, Mourad Tayebi
Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides...
2018: Frontiers in Aging Neuroscience
Kate M Franz, William J Neidermyer, Yee-Joo Tan, Sean P J Whelan, Jonathan C Kagan
In mammalian cells, IFN responses that occur during RNA and DNA virus infections are activated by distinct signaling pathways. The RIG-I-like-receptors (RLRs) bind viral RNA and engage the adaptor MAVS (mitochondrial antiviral signaling) to promote IFN expression, whereas cGAS (cGMP-AMP synthase) binds viral DNA and activates an analogous pathway via the protein STING (stimulator of IFN genes). In this study, we confirm that STING is not necessary to induce IFN expression during RNA virus infection but also find that STING is required to restrict the replication of diverse RNA viruses...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tasuku Kitada, Breanna DiAndreth, Brian Teague, Ron Weiss
Gene and engineered-cell therapies promise to treat diseases by genetically modifying cells to carry out therapeutic tasks. Although the field has had some success in treating monogenic disorders and hematological malignancies, current approaches are limited to overexpression of one or a few transgenes, constraining the diseases that can be treated with this approach and leading to potential concerns over safety and efficacy. Synthetic gene networks can regulate the dosage, timing, and localization of gene expression and therapeutic activity in response to small molecules and disease biomarkers...
February 9, 2018: Science
Yili Qian, Domitilla Del Vecchio
A major problem in the design of synthetic genetic circuits is robustness to perturbations and uncertainty. Because of this, there have been significant efforts in recent years in finding approaches to implement integral control in genetic circuits. Integral controllers have the unique ability to make the output of a process adapt perfectly to disturbances. However, implementing an integral controller is challenging in living cells. This is because a key aspect of any integral controller is a 'memory' element that stores the accumulation (integral) of the error between the output and its desired set-point...
February 2018: Journal of the Royal Society, Interface
Protyusha Dey, Amit Roy
Industrial applications of xylanases have made this enzyme an important subject of applied research work. Function of this particular enzyme is to degrade or hydrolyze the plentiful polysaccharide xylan, an important component of hemicellulose. It mainly cleaves the backbone of xylan that is made up of a number of xylose residues connected with β-1,4-glycosidic linkages. Fungi with mycelia are regarded as the best producer of xylanases. These varied xylanases not only differ in their sizes and shapes but also differ in their physicochemical properties...
February 2018: 3 Biotech
Young Je Lee, Soo-Jung Kim, Tae Seok Moon
Synthetic small RNA regulators have emerged as a versatile tool to predictably control bacterial gene expression. Owing to their simple design principles, small size, and highly orthogonal behavior, these engineered genetic parts have been incorporated into genetic circuits. However, efforts to achieve more sophisticated cellular functions using RNA regulators have been hindered by our limited ability to integrate different RNA regulators into complex circuits. Here, we present a combined RNA regulatory system in Escherichia coli that uses small transcription activating RNA (STAR) and antisense RNA (asRNA) to activate or deactivate target gene expression in a programmable manner...
February 11, 2018: ACS Synthetic Biology
Katherine E Marusak, Julia R Krug, Yaying Feng, Yangxiaolu Cao, Lingchong You, Stefan Zauscher
The emerging field of biofabrication capitalizes on nature's ability to create materials with a wide range of well-defined physical and electronic properties. Particularly, there is a current push to utilize programmed, self-organization of living cells for material fabrication. However, much research is still necessary at the interface of synthetic biology and materials engineering to make biofabrication a viable technique to develop functional devices. Here, the authors exploit the ability of Escherichia coli to contribute to material fabrication by designing and optimizing growth platforms to direct inorganic nanoparticle (NP) synthesis, specifically cadmium sulfide (CdS) NPs, onto porous polycarbonate membranes...
February 9, 2018: Biointerphases
Miguel-Angel Perales, Partow Kebriaei, Leslie S Kean, Michel Sadelain
Therapeutic T cell engineering has recently garnered widespread interest because of the success of CD19 chimeric antigen receptor (CAR) therapy. CARs are synthetic receptors for antigen that redirect the specificity and reprogram the function of the T cells in which they are genetically introduced. CARs targeting CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded high remission rates in patients with chemorefractory, relapsed disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma...
March 2018: Biology of Blood and Marrow Transplantation
Monika Toma, Tomasz Skorski, Tomasz Sliwinski
Cancer is a heterogeneous disease with a high degree of diversity between and within tumors. Our limited knowledge of their biology results in ineffective treatment. However, personalized approach may represent a milestone in the field of anticancer therapy. It can increase specificity of treatment against tumor initiating cancer stem cells (CSCs) and cancer progenitor cells (CPCs) with minimal effect on normal cells and tissues. Cancerous cells carry multiple genetic and epigenetic aberrations which may disrupt pathways essential for cell survival...
January 31, 2018: Current Medicinal Chemistry
Nicholas Ting Xun Ong, Jeffrey J Tabor
Genetically-engineered photoreceptors enable unrivaled control over gene expression. Previously, we ported the Synechocystis PCC 6803 CcaSR two-component system, which is activated by green light and de-activated by red, into E. coli, resulting in a sensor with 6-fold dynamic range. Later, we optimized pathway protein expression levels and the output promoter sequence to decrease transcriptional leakiness and increase the dynamic range to approximately 120-fold. These CcaSR v1.0 and 2.0 systems have been used for precise quantitative, temporal, and spatial control of gene expression for a variety of applications...
February 8, 2018: Chembiochem: a European Journal of Chemical Biology
Julia Legen, Stephanie Ruf, Xenia Kroop, Gongwei Wang, Alice Barkan, Ralph Bock, Christian Schmitz-Linneweber
The chloroplast is a prime target for genetic engineering in plants, offering various advantages over nuclear transformation. For example, chloroplasts allow the expression of polycistronic transcripts and thus to engineer complex metabolic pathways. Each cistron within such a longer transcript needs its own expression elements. Within the 5'-UTR, such expression elements are needed for stabilizing mRNAs and for translation of the downstream reading frame. One of the few effective expression elements used so far in transplastomic approaches is the intercistronic expression element (IEE)...
February 8, 2018: Plant Journal: for Cell and Molecular Biology
Taylor Firman, Stephen Wedekind, Thomas J McMorrow, Kingshuk Ghosh
Gene networks with feedback often involve interactions between multiple species of bio-molecules, much more than experiments can actually monitor. Coupled with this is the challenge that experiments often measure gene expression in noisy fluorescence instead of protein numbers. How do we infer biophysical information and characterize the underlying circuits from this limited and convoluted data? We address this by building stochastic models using the principle of Maximum Caliber (MaxCal). MaxCal uses the basic information of synthesis, degradation, and feedback -- without invoking any other auxiliary species and ad hoc reactions -- to generate stochastic trajectories similar to those typically measured in experiments...
February 6, 2018: Journal of Physical Chemistry. B
Mathis Baalmann, Marcel Best, Richard Wombacher
Here, we describe a two-step protocol for selective protein labeling based on enzyme-mediated peptide labeling utilizing lipoic acid ligase (LplA) and bioorthogonal chemistry. The method can be applied to purified proteins, protein in cell lysates, as well as living cells. In a first step a W37V mutant of the lipoic acid ligase (LplAW37V) from Escherichia coli is utilized to ligate a synthetic chemical handle site-specifically to a lysine residue in a 13 amino acid peptide motif-a short sequence that can be genetically expressed as a fusion with any protein of interest...
2018: Methods in Molecular Biology
Eszter Kozma, Giulia Paci, Gemma Estrada Girona, Edward A Lemke, Péter Kele
Tetrazine-bearing fluorescent labels enable site-specific tagging of proteins that are genetically manipulated with dienophile modified noncanonical amino acids. The inverse electron demand Diels-Alder reaction between the tetrazine and the dienophile fulfills the criteria of bioorthogonality allowing fluorescent labeling schemes of live cells. Here, we describe the detailed synthetic and labeling protocols of a near infrared emitting siliconrhodamine-tetrazine probe suitable for super-resolution imaging of residue-specifically engineered proteins in mammalian cells...
2018: Methods in Molecular Biology
Lei Yan, Zhenshan Liu, Huanwen Xu, Xiaoping Zhang, Aiju Zhao, Fei Liang, Mingming Xin, Huiru Peng, Yingyin Yao, Qixin Sun, Zhongfu Ni
BACKGROUND: Common wheat is a typical allohexaploid species (AABBDD) derived from the interspecific crossing between allotetraploid wheat (AABB) and Aegilops tauschii (DD). Wide variation in grain size and shape observed among Aegilops tauschii can be retained in synthetic allohexaploid wheats, but the underlying mechanism remains enigmatic. Here, the natural and resynthesized allohexaploid wheats with near-identical AB genomes and different D genomes (TAA10 and XX329) were employed for analysis...
February 5, 2018: BMC Plant Biology
Austin Burt, Andrea Crisanti
Drive is a process of accelerated inheritance from one generation to the next that allows some genes to spread rapidly through populations even if they do not contribute to-or indeed even if they detract from-organismal survival and reproduction. Genetic elements that can spread by drive include gametic and zygotic killers, meiotic drivers, homing endonuclease genes, B chromosomes, and transposable elements. The fact that gene drive can lead to the spread of fitness-reducing traits (including lethality and sterility) makes it an attractive process to consider exploiting to control disease vectors and other pests...
February 5, 2018: ACS Chemical Biology
Awad A E Elbashir, Yasir S A Gorafi, Izzat S A Tahir, Ashraf M A Elhashimi, Modather G A Abdalla, Hisashi Tsujimoto
In wheat (Triticum aestivum L.) high temperature (≥30°C) during grain filling leads to considerable reduction in grain yield. We studied 400 multiple synthetic derivatives (MSD) lines to examine the genetic variability of heat stress-adaptive traits and to identify new sources of heat tolerance to be used in wheat breeding programs. The experiment was arranged in an augmented randomized complete block design in four environments in Sudan. A wide range of genetic variability was found in most of the traits in all environments...
December 2017: Breeding Science
Celia Blanco, Marco Bayas, Fu Yan, Irene A Chen
A central difficulty facing study of the origin of life on Earth is evaluating the relevance of different proposed prebiotic scenarios. Perhaps the most established feature of the origin of life was the progression through an RNA World, a prebiotic stage dominated by functional RNA. We use the appearance of proteins in the RNA World to understand the prebiotic milieu and develop a criterion to evaluate proposed synthetic scenarios. Current consensus suggests that the earliest amino acids of the genetic code were anionic or small hydrophobic or polar amino acids...
January 29, 2018: Current Biology: CB
Ryo Nishijima, Chisa Tanaka, Kentaro Yoshida, Shigeo Takumi
Cuticular wax on the aerial surface of plants has a protective function against many environmental stresses. The bluish-whitish appearance of wheat leaves and stems is called glaucousness. Most modern cultivars of polyploid wheat species exhibit the glaucous phenotype, while in a wild wheat progenitor, Ae. tauschii, both glaucous and non-glaucous accessions exist. Iw2, a wax inhibitor locus on the short arm of chromosome 2D, is the main contributor to this phenotypic variation in Ae. tauschii, and the glaucous/non-glaucous phenotype of Ae...
February 3, 2018: Genetica
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