Researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
dam Bogdanove, associate professor in plant pathology, was researching the molecular basis of bacterial diseases of rice when he and Matthew Moscou, a student in the bioinformatics and computation biology graduate program, discovered that the so-called TAL effector proteins injected into plant cells by strains of the bacterium Xanthomonas attach at specific locations to host DNA molecules.
They found that different proteins of this class bind to different DNA locations, and particular amino acids in each protein determine those locations, called binding sites, in a very straightforward way.
"When we hit on it, we thought, 'Wow, this is so simple, it's ridiculous,'" Bogdanove said. Bogdanove's research will be published in an upcoming issue of the journal Science and is highlighted in last week's Science Express, an early online edition for research the Science editors feel is particularly timely and important. The paper is being published alongside a study from another research team that arrived at the same conclusions independently.
In his research, Bogdanove was examining how Xanthomonas uses TAL effectors to manipulate gene function in plants in ways that benefit the pathogen. Bogdanove was specifically interested in how different TAL effector proteins are able to activate different corresponding plant genes.
Over the past decade, understanding of this unique class of proteins has grown in leaps and bounds, according to Bogdanove.
Researchers in Germany, at Kansas State University, Manhattan; and here at Iowa State (Bing Yang, assistant professor in genetics development and cell biology) had previously shown that these proteins bind host DNA and activate genes important for disease, or in some cases defense against the bacteria. But no one yet understood how different TAL effectors recognized different parts of the DNA in order to attach and turn on the different genes at those locations.
Through computer analyses, Bogdanove and Moscou discovered that pairs of amino acids distributed throughout a TAL effector protein each specify a particular nucleotide, one of the bases in DNA abbreviated as the letters G, A, T, or C. The complete set of these pairs directs the protein to a matching string of Gs, As, Ts, and Cs in the DNA.
"This simple relationship allows us to predict where a TAL effector will bind, and what genes it will activate. It also makes it likely that we can custom engineer TAL effectors to bind to virtually any DNA sequence," says Bogdanove.
According to Bogdanove, being able to predict TAL effector binding sites will lead quickly to the identification of plant genes that are important in disease. Natural variants that lack these binding sites are a potential source of disease resistance.
Another potential application is adding TAL effector binding sites to defense-related genes so they are activated upon infection.
The possibilities for this new technology extend beyond plant disease control, according to Bogdanove.
"We might be able to use TAL effectors to activate genes in non-plant cells, possibly even in human stem cells for gene therapy. Or we might be able to use them to modify DNA at specific locations and help us study gene function. This could apply in many areas, including cancer research, for example," he said.
Bogdanove said the simplicity of the results surprised the research team.
"A predictable and potentially customizable kind of protein-DNA binding has been hard to find in nature. As Matt and I talked about the possibilities, we got excited and one of us said -- I don't remember who -- 'We've got to submit this to Science, dude,'" said Bogdanove.
Moscou investigated TAL effector DNA binding with Bogdanove through his participation in the Bioinformatics and Computation Biology (BCB) Lab, a student-run organization that provides assistance with computational analyses for life science researchers on campus. Moscou is a founding member of the BCB Lab, which is supported by a training grant to the BCB graduate program from the National Science Foundation. Moscou is doing his dissertation research on a plant pathogenic fungus under Roger Wise, professor in plant pathology.
Research in the Bogdanove laboratory is supported by funding from the NSF Plant Genome Research Program and from the United Stated Department of Agriculture -- Agricultural and Food Research Initiative program.
------------------------------------------------------------------------------------------------
Iowa State University (2009, November 13). Researcher Discovers Key To Vital DNA, Protein Interaction. ScienceDaily. Retrieved November 14, 2009, from http://www.sciencedaily.com /releases/2009/11/091110171654.htm
Friday
Sunday
Modified Crops Reveal Hidden Cost Of Resistance
Genetically modified squash plants that are resistant to a debilitating viral disease become more vulnerable to a fatal bacterial infection, according to biologists. "Cultivated squash is susceptible to a variety of viral diseases and that is a major problem for farmers," said Andrew Stephenson, Penn State professor of biology. "Infected plants grow more slowly and their fruit becomes misshapen."
In the mid-1990s, the U.S. Department of Agriculture approved genetically modified squash, which are resistant to three of the most important viral diseases in cultivated squash. However, while disease-resistant crops have been a boon to commercial farmers, ecologists worry there might be certain hidden costs associated with the modified crops.
"There is concern in the ecological community that, when the transgenes that confer resistance to these viral diseases escape into wild populations, they will (change) those plants," said Stephenson, whose team's findings appeared Oct. 26 in the Proceedings of the National Academy of Sciences. "That could impact the biodiversity of plant communities where wild squash are native."
Stephenson and his colleagues James A. Winsor, professor of biology; Matthew J. Ferrari, research associate; and Miruna A. Sasu, doctoral student, all at Penn State; and Daolin Du, visiting professor, Jiangsu University, China, crossed the genetically modified squash into wild squash native to the southwestern United States and examined the resulting flower and fruit production.
Unlike a lab experiment, the researchers tried to mimic a real world setting during their three-year study.
The researchers then looked at the effects of the virus-resistant transgenes on prevalence of the three viral diseases, herbivory by cucumber beetles, as well as the occurrence of bacterial wilt disease that is spread by the cucumber beetles.
"When the cucumber beetles start to feed on infected plants they pick up the bacteria through their digestive system," explained Sasu. "This feeding creates open wounds on the leaves and when the bugs' feces falls on these open wounds, the bacteria find their way into the plumbing of the plant."
The researchers discovered that as the viral infection swept the fields containing both genetically modified and wild crops, the damage from cucumber beetles is greater on the genetically modified plants. The modified plants are therefore more susceptible to the fatal bacterial wilt disease.
"Plants that do not have the virus-resistant transgene get the viral disease," explained Stephenson, whose team's work is funded by the National Science Foundation. "However, since cucumber beetles prefer to feed on healthy plants rather than viral infected plants, the beetles become increasingly concentrated on the healthy -- mostly transgenic -- plants."
During a viral epidemic, the transgene provides modified plants with a fitness advantage over the wild plants. But when both the bacterial and viral pathogens are present, the beetles tend to avoid the smaller viral infected plants and concentrate on the healthy transgenic plants. This exposes those plants to the bacterial wilt disease against which they have no defense.
"Wild and transgenic plants had the same amount of damage from beetles before viral diseases were prevalent in our fields," said Stephenson. "Once the virus infected the wild plants, the transgenic plants had significantly greater damage from the beetles."
Results from the study show that over the course of three years, the prevalence of bacterial wilt disease was significantly greater on transgenic plants than on non-transgenic plants.
According to the researchers, their findings suggest that the fitness advantage enjoyed by virus-resistant plants comes at a price. Once the virus infects susceptible plants, cucumber beetles find the genetically modified plants a better source for food and mating.
"Our study has sought to uncover the ecological cost that might be associated with modified plants growing in the full community of organisms, including other insects and other diseases," said Ferrari. "We have shown that while genetic engineering has provided a solution to the problem of viral diseases, there are also these unintended consequences in terms of additional susceptibility to other diseases."
----------------------------------------------------------------------------------------------
Adapted from materials provided by Penn State.