“It actually sucks the arsenic out of the soil and puts it in the fronds,” Banks said. “It’s the only multi-cellular organism that can do this.”

Without a genome sequenced for Pteris vittata, Banks and Salt used a method of gene identification called yeast functional complementation. They combined thousands of different Pteris vittata genes into thousands of yeast cells that were missing a gene that makes them tolerant to arsenic.

The yeast was exposed to arsenic, with most of it dying. The yeast strains that lived had picked up the genes from Pteris vittata that convey arsenic resistance.

To confirm that this was the correct gene, its function was knocked down and the plant was exposed to arsenic. Without the gene functioning properly, the plant could not tolerate arsenic.

“It tells us that this gene is necessary for the plant to function on arsenic,” said Banks, whose findings were published in the early online version of the journal Plant Cell. “We looked for a similar gene in the plant Arabidopsis. We couldn’t find it. It can’t be found in any flowering plant.”

Banks and Salt found that the protein encoded by this gene ends up in the membrane of the plant cell’s vacuole. Salt said the protein acts as a pump, moving arsenic into the cell’s equivalent of a trashcan.

“It stores it away from the cytoplasm so that it can’t have an effect on the plant,” Salt said.

Banks said understanding how the Pteris vittata functions with arsenic could lead to ways to clean up arsenic-contaminated land.

“Potentially you could take these genes and put them in any organism that could suck the arsenic out of the soil,” Banks said.

Salt said rice plants could be modified with the gene to store arsenic in the roots of plants — instead of rice grains — in contaminated paddies.

Banks and Salt found another gene in Pteris vittata that looks almost exactly the same as the one that controls arsenic tolerance. When the fern was exposed to arsenic, the confirmed arsenic-tolerance gene increased its expression while the similar gene did not.

Salt said the gene that regulates arsenic tolerance could be a duplicate of the other that has changed slightly to give itself a new function.

“The fact that it has these two genes could be a sign of evolution,” Salt said. “One of the thoughts of gene evolution is that one copy could continue to do what it has always done, while the duplicate can develop another function.”

The plant might have evolved to accumulate arsenic, Banks and Salt theorized, as a defense against animals or insects eating them.

Banks hopes findings such as this will lead to more research emphasis on non-flowering plants. She said there are characteristics in plants such as Pteris vittata that cannot be found in other organisms.

The next step in their research is to put the arsenic-tolerance gene from Pteris vittata into Arabidopsis to see whether it gives the new plant the same characteristics.

The National Science Foundation funded the research.

Source:Science Daily.com

Starting July 1, the Centerstone Career Resource Center will operate from offices in Tullahoma and Columbia, Tenn. The center is funded with a $5 million federal stimulus grant.

The center is expected to create nearly 300 new jobs through offering health care education opportunities, job training, employment placement assistance and support services to 600 people in five Middle Tennessee counties: Bedford, Coffee, Lawrence, Marshall and Maury.

Centerstone is partnering with the local schools and hospitals and government entities such as the Tennessee Department of Labor and Workforce Development to offer the training and to create jobs. The center also will offer participants assistance such as help with child-care and interview preparation training.

The center will begin reviewing potential participants on June 15. More information about the center is available at www.centerstone.org/careerresourcecenter or 1-888-519-5190.

“We are rapidly entering a time when nearly anyone can have his or her genome sequenced,” said Michael Snyder, PhD, professor and chair of genetics at Stanford. “However, the bulk of the differences among individuals are not found in the genes themselves, but in regions we know relatively little about. Now we see that these differences profoundly impact protein binding and gene expression.”

Snyder is the senior author of two papers — one in Science Express and one in Nature — exploring these protein-binding differences in humans, chimpanzees and yeast. Snyder, the Stanford W. Ascherman, MD, FACS, Professor in Genetics, came to Stanford in July 2009 from Yale, where much of the work was conducted.

Genes, which carry the specific instructions necessary to make proteins do the work of the cell, vary by only about 0.025 percent across all humans. Scientists have spent decades trying to understand how these tiny differences affect who we are and what we become. In contrast, non-coding regions of the genome, which account for approximately 98 percent of our DNA, vary in their sequence by about 1 to 4 percent. But until recently, scientists had little, if any, idea what these regions do and how they contribute to the “special sauce” that makes me, me, and you, you.

Now Snyder and his colleagues have found that the unique, specific changes among individuals in the sequence of DNA affect the ability of “control proteins” called transcription factors to bind to the regions that control gene expression. As a result, the subsequent expression of nearby genes can vary significantly.

“People have done a lot of work over the years to characterize differences in gene expression among individuals,” said Snyder. “We’re the first to look at differences in transcription-factor binding from person to person.” What’s more, by selectively breeding, or crossing, yeast strains, Snyder and his colleagues found that many, but not all, of these differences in binding and expression levels are heritable.

In the Science Express paper, which will be published online March 18, Snyder and his colleagues compared the binding patterns of two transcription factors in 10 people and one chimpanzee. They identified more than 15,000 binding sites across the genome for the transcription factor called NF-kB and more than 19,000 sites for another factor called RNA PolII. They then looked to see if every site was bound equally strongly by the proteins, or if there were variations among individuals.

They found that about 25 percent of the PolII sites and 7.5 percent of the NF-kB sites exhibited significant binding differences among individuals — in some cases greater than two orders of magnitude from one person to another. (For comparison, the binding differences between the humans and the chimpanzee were about 32 percent.) Many of these binding differences could be traced to differences in sequences or structure in the protein binding sites, and several were directly correlated to changes in gene expression levels.

“These binding regions, or chunks, vary among individuals,” said Snyder, “and they have a profound impact on gene expression.” In particular, the researchers found that several of the variable binding regions were near genes involved in such diseases as type-1 diabetes, lupus, leukemia and schizophrenia.

The researchers confirmed and extended their findings in the Nature paper, which will be published online March 17. In this study, they used yeast to determine that many of the binding differences and variations in gene expression levels in individuals are passed from parent to progeny, and they identify several control proteins that vary — a study that would have been impossible to perform in humans.

“We conducted the two studies in parallel,” said Snyder, “and found the same thing. Many of the binding sites differed. When we mapped the areas of difference, we found that they were associated with key regulators of variation in the population. Together these two studies tell us a lot about the so-called regulatory code that controls variation among individuals.”

The research in the Science Express study was supported by the National Institutes of Health, the European Molecular Biology Laboratory and the Howard Hughes Medical Institute’s Medical Fellows Program. The research in the Nature study was supported by the National Institutes of Health. In addition to Snyder, other Stanford researchers involved in the two studies include postdoctoral scholars Fabian Grubert, PhD; Minyi Shi, PhD; and Manoj Hariharan, PhD; and graduate student Konrad Karczewski.

The team’s work focused on a neurotransmitter that typically plays an important role in communication among nerve cells in the brain and fosters learning and memory. This glutamate neurotransmitter opens the NMDA (N-methyl-D-aspartate) receptors, allowing the entry of calcium into the nerve cells.

Under normal conditions, the activity of the NMDA receptors is tightly regulated to prevent nerve cells from becoming overloaded with calcium. During a stroke, however, that process of regulation breaks down. The excessive influx of calcium through NMDA receptors kills the nerve cells and can cause severe brain damage.

Striving to prevent such calcium overloads, the research team discovered that an enzyme, DAPK1 (Death-Associated Protein Kinase 1), binds to a portion of the NMDA receptor and acts as a “cell death signal” during strokes.

Researchers hypothesized that by preventing DAPK1 from binding with the NMDA receptors, they could prevent the calcium overloads and cell deaths. They developed a potent compound to test their theory and found that the compound blocked DAPK1, protecting brain cells against stroke injury, and did not affect the beneficial physiological functions of the receptors.

The findings appear in the Jan. 22 issue of Cell, one of the leading journals in the field.

“It is conceivable that this study not only provides new insights into the cellular and molecular basis responsible for stroke damage, but also provides a therapeutic target for stroke therapy,” said Youming Lu, the LSU professor who led the team of scientists.

The findings also may have significant implications for developing therapeutic drugs to treat other neurodegenerative diseases, said UCF Assistant Professor Sic Chan, a study collaborator who has done extensive research on the role of calcium in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

“Anytime we gain an increased understanding of the molecular mechanism of neurodegeneration, that enhances our ability to make better drugs,” he said.

To date, all stroke clinical trials targeting glutamate receptors have failed, largely because of their side effects, an inefficient delivery of compounds from the blood to the brain or the length of time it takes for the drugs to work effectively.

Their latest achievement, detailed in a paper published in the January 21 issue of the journal Nature, is a crucial step in creating genetic sensors that might one day provide humans with advance information about temperature, poisons and other potential hazards in the environment by monitoring changes in the bacterium’s blinking rates.

“Programming living cells is one defining goal of the new field of synthetic biology,” said Jeff Hasty, associate professor of biology and bioengineering at UCSD who headed the research team with Lev Tsimring, associate director of UCSD’s BioCircuits Institute.

“Dr. Hasty and colleagues have used powerful genetic tools, backed by decades of detailed knowledge of bacterial processes, to create a system that delivers on the promise of synthetic biology — to engineer living organisms to meet pressing societal needs,” said James Anderson, who oversees computational biology grants at the NIH’s National Institute of General Medical Sciences. “The oscillating system they engineered sets the stage for the development of highly sensitive sensors that could have multiple applications in basic research, biotechnology and medicine.”

“Synchronization of clocks and oscillators in general has been a fascinating subject for physicists and applied mathematicians for centuries,” said Tsimring. “This began with the Dutch mathematician and astronomer Christiaan Huygens, who is credited with its serendipitous discovery in 1665 when he suspended a pair of nearly identical pendulum clocks (which he invented and patented some 8 years earlier) on the same wooden beam.”

“Synchronization plays a crucial role in physics and biology as a way of self-organization of highly regular behavior with less that perfect components. This phenomenon has a myriad of applications in modern technology, from communication networks to GPS. Our study demonstrates how inherently noisy gene oscillators can operate together with beautiful synchronicity and regularity once coupled together in a specific way.”

Over the past decade, researchers have gone from wiring genetic toggle switches and oscillators in living cells to building living circuits capable of pattern generation, noise shaping, edge detection and event counting. In their latest development, the UCSD researchers took advantage of a type of bacterial communication in which bacteria exchange small molecules.

“Many bacteria species are known to communicate by a mechanism known as quorum sensing, that is, relaying between them small molecules to trigger various behaviors,” said Hasty. “Other bacteria are known to disrupt this communication mechanism by degrading these relay molecules.”

Taking these communication elements from different organisms, Hasty and his team of researchers — who included UCSD bioengineering graduate students Tal Danino and Octavio Mondragon — designed and constructed a network in the genetic model bacterium E. coli with positive and negative feedback components to produce a colony of synchronized clocks.

Hasty said the architecture of the circuit is similar to his team’s previous genetic clock (see: here), but with the quorum sensing components allowing the phase information — that is, the oscillations between the bacterial cells — to be relayed.

The researchers constructed devices to precisely control the sizes of the bacterial colonies between two different scales: a micron, or a millionth of a meter, and a millimeter, or one-thousandth of a meter. At the micron scales, Hasty said the cells in the colonies oscillate synchronously from 50 to 90 minutes, a period that can be tuned externally. But at the longer, or millimeter scales, he noted, the time for diffusion of the signal becomes more important, allowing the researchers to actually observe the propagation of the signal through the colony.

“The use of quorum sensing is a promising approach to increase the sensitivity and robustness of the dynamic response to external signals,” said Hasty. “In nature, synchronization typically helps stabilize a desired behavior arising from a network of intrinsically noisy and unreliable elements. We think the synchronized genetic clock sets the stage for the use of microbes as a macroscopic biosensor with oscillatory output, or applications of using a synchronized periodic signal in drug delivery.”

The scientists received funding for their development from the National Institute of General Medical Sciences, which is part of the National Institutes of Health.