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Urbana, IL, United States

Sun N.,University of Illinois at Urbana - Champaign | Liang J.,University of Illinois at Urbana - Champaign | Abil Z.,University of Illinois at Urbana - Champaign | Zhao H.,University of Illinois at Urbana - Champaign | Zhao H.,Institute for Genomic Biology
Molecular BioSystems | Year: 2012

TAL effector nucleases (TALENs) represent a new class of artificial nucleases capable of cleaving long, specific target DNA sequences in vivo and are powerful tools for genome editing with potential therapeutic applications. Here we report a pair of custom-designed TALENs for targeted genetic correction of the sickle cell disease mutation in human cells, which represents an example of engineered TALENs capable of recognizing and cleaving a human disease-associated gene. By using a yeast reporter system, a systematic study was carried out to optimize TALEN architecture for maximal in vivo cleavage efficiency. In contrast to the previous reports, the engineered TALENs were capable of recognizing and cleaving target binding sites preceded by A, C or G. More importantly, the optimized TALENs efficiently cleaved a target sequence within the human β-globin (HBB) gene associated with sickle cell disease and increased the efficiency of targeted gene repair by >1000-fold in human cells. In addition, these TALENs showed no detectable cytotoxicity. These results demonstrate the potential of optimized TALENs as a powerful genome editing tool for therapeutic applications. © 2012 The Royal Society of Chemistry. Source

Tippana R.,University of Illinois at Springfield | Xiao W.,University of Illinois at Springfield | Myong S.,University of Illinois at Springfield | Myong S.,Institute for Genomic Biology | Myong S.,Urbana University
Nucleic Acids Research | Year: 2014

The quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynamics of GQ forming sequences measured by single molecule fluorescence. Additionally, we relate these properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our result shows that both the loop (non-G components) length and sequence contribute to the conformation of the GQ. Real time single molecule traces reveal that the folding dynamics also depend on the loop composition. We demonstrate that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation. Our findings point to the complexity of GQ folding governed by the loop length and sequence and how the GQ conformation determines the small molecule and protein binding propensity. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. Source

Shen W.,UNC Greensboro | Gaskins H.R.,Institute for Genomic Biology | McIntosh M.K.,UNC Greensboro
Journal of Nutritional Biochemistry | Year: 2014

Recent studies using germ-free, gnotobiotic microbial transplantation/conventionalization or antibiotic treatment in rodent models have highlighted the critical role of intestinal microbes on gut health and metabolic functions of the host. Genetic and environmental factors influence the abundance and type of mutualistic vs. pathogenic bacteria, each of which has preferred substrates for growth and unique products of fermentation. Whereas some fermentation products or metabolites promote gut function and health, others impair gut function, leading to compromised nutrient digestion and barrier function that adversely impact the host. Such products may also influence food intake, energy harvest and expenditure, and insulin action, thereby influencing adiposity and related metabolic outcomes. Diet composition influences gut microbiota and subsequent fermentation products that impact the host, as demonstrated by prebiotic studies using oligosaccharides or other types of indigestible fiber. Recent studies also show that dietary lipids affect specific populations of gut microbes and their metabolic end products. This review will focus on studies examining the influence of dietary fat amount and type on the gut microbiome, intestinal health and positive and negative metabolic consequences. The protective role of omega-3-rich fatty acids on intestinal inflammation will also be examined. © 2014 Elsevier Inc. Source

News Article
Site: http://phys.org/biology-news/

Plant scientists at Lancaster University, Rothamsted Research, and The International Maize and Wheat Improvement Center (CIMMYT) have been investigating a naturally occurring plant enzyme known as Rubisco to explore its ability to boost photosynthesis and increase crop yields. In a new paper published this month, the team measured photosynthesis in 25 genotypes of wheat—including wild relatives of bread wheat (Triticum aestivum)—and found variation exists even amongst closely related genotypes. Each type was surveyed to identify superior Rubisco enzymes for improving photosynthesis. Two of the most efficient were Rubisco from plants known as Aegilops cylindrica (jointed goatgrass) and Hordeum vulgare (barley), which both showed promising Rubisco catalytic properties that should be explored in the context of improving photosynthesis, and ultimately grain yield, in wheat. Models suggest that incorporating the new enzymes into wheat could increase photosynthesis by up 20% under some field conditions. Wheat is a crucial source of food, providing more than 20 per cent of the calories consumed worldwide. And with projections that the world population will rise to over nine billion by the year 2050, the pressure is on to meet global demand for food. Professor Martin A. J. Parry of the Lancaster Environment Centre (LEC) said: "Improving the efficiency of photosynthesis—the way crops turn carbon dioxide in our atmosphere into everything we can eat—may seem ambitious but for us it offers the best opportunity for producing the scale of change in crop yield that we need to feed a growing global population in a changing world climate." Elizabete Carmo-Silva, LEC lecturer in plant sciences for food security, said: "Both jointed grass and barley are regarded as valuable genetic resources for improving wheat disease resistance, our research suggests that they can also be used to improve biomass production." Research associates Anneke Prins and Doug Orr conducted the experimental work which was jointly funded by CIMMYT (W4031.11 Global Wheat Program) and by Realizing Increased Photosynthetic Efficiency, a project funded by the Bill & Melinda Gates Foundation and led by the University of Illinois at the Carl R. Woese Institute for Genomic Biology. "This is an exciting piece of work showing that Rubisco catalytic properties vary in close relatives of wheat," Orr said. "As part of the RIPE project, we are screening a wide range of species from across the globe, and aim to identify variation that will enable improving photosynthesis and biomass production in rice, cassava and soybean." Explore further: Algal genes may boost efficiency, yield in staple crops More information: The paper 'Rubisco catalytic properties of wild and domesticated relatives provide scope for improving wheat photosynthesis' was published in the Journal of Experimental Botany Advance Access.

News Article
Site: http://phys.org/biology-news/

Photosynthesis is the process in which plants turn light energy and carbon dioxide into food and fuel. In full sun, plants receive more energy than they can use. The extra energy could generate damaging molecules, but instead, plants siphon this energy off as heat to protect themselves. When a cloud passes overhead, plants are slow to recover from this protective process, called non-photochemical quenching, or NPQ. "It can take minutes to hours for the plant to fully recover and begin photosynthesizing at maximum capacity again," said lead author Krishna Niyogi, a professor at the University of California, Berkeley. "We are trying to figure out how to speed up the plant's recovery from NPQ, which models predict could increase yields by 10 to 15 percent." Niyogi and co-authors are searching for mechanisms that plants and algae naturally evolved to recover faster from NPQ. This work was published in Plant Journal and is part of Realizing Increased Photosynthetic Efficiency, a multi-institutional research project funded by the Bill & Melinda Gates Foundation and led by the University of Illinois at the Carl R. Woese Institute for Genomic Biology. "The method developed here will greatly accelerate the search for means to improve photosynthetic efficiency under conditions of varying light," said lead author Steve Long, Gutgsell Endowed Professor of Plant Biology and Crop Sciences at Illinois. Before implementing this technique, they could quickly sequence the DNA of these organisms, but lacked the biological tools to quickly figure out the genes responsible for desirable traits. They would have had to spend weeks or months creating gene constructs, inserting them into plants, growing the plants, and ensuring that the gene had been expressed. Now, in a matter of days, these researchers can compare multiple genes side-by-side on the same leaf using transient expression, a temporary technique to evaluate gene function used extensively by plant pathologists. With transient expression, the gene is expressed for a few days and then the effect on the leaf is tested. Researchers swap out the genes from a bacterium that, in nature, produce tumorous growths on the roots of flowering plants with the genes that might speed recovery from NPQ. NPQ is incredibly complex. At least four different mechanisms, with different rates of recovery, collectively make up NPQ. The fastest mechanism is mediated by a tug-of-war between two enzymes. In this study, researchers evaluated how overexpressing these enzymes affected NPQ. They also evaluated three distantly related proteins (from a unicellular alga, a moss, and a small flowering plant) that are thought to activate the fastest mechanism; they found that the protein from the moss had the fastest activation and greatest capacity to recover from NPQ. Finally, they confirmed the function of genes from two species of oceanic algae, which are emerging model organisms. One of these genes enabled the plant to produce a pigment that has been shown to improve energy transfer. Ultimately, this technique speeds up the research process. Now researchers can use this technique to quickly identify the genes needed to increase the yields of staple food crops. Through "global access," pledged by the Bill & Melinda Gates Foundation, the outcome of this work may one day benefit smallholder farmers, especially those working to sustain their communities in Sub-Saharan Africa and Southeastern Asia. Explore further: Gene protects against toxic byproducts of photosynthesis, helping plants to 'breathe' More information: Lauriebeth Leonelli et al, Transient expression infor rapid functional analysis of genes involved in non-photochemical quenching and carotenoid biosynthesis, The Plant Journal (2016). DOI: 10.1111/tpj.13268

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