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onishadowolf:
New cellular 'bones' revealed
Filament-making proteins offer hints to cell structure
By Tina Hesman Saey
Web edition : Monday, December 13th, 2010
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PHILADELPHIA — Scientists may have uncovered a new type of skeleton in cells’ closets.

Cells harbor several newly discovered types of filaments, Jim Wilhelm of the University of California, San Diego reported December 12 at the annual meeting of the American Society for Cell Biology. These filaments, formed from strings of metabolic proteins, could give researchers clues about how the cell’s internal skeleton evolved.

In experiments with yeast, Wilhelm and his colleagues discovered that an enzyme called CTP synthase can make filaments. The enzyme produces a molecule that is similar to ATP, a cell’s main energy currency. CTP is necessary for many chemical reactions, which it participates in and also fuels.

The team found that when CTP levels in the cell rise in yeast, the enzyme forms filaments.

Fruit flies also harbor CTP synthase filaments in their egg cells, the researchers demonstrated. At about the same time, other research groups discovered filaments of the enzyme in bacteria and in human brain cells. Wilhelm says the researchers don’t yet know if the filaments help form the cellular skeleton in the human, fruit fly and yeast cells in which they are found. But another group showed that the filaments do affect the shape of some bacterial cells.

The discovery of the filaments in organisms as diverse as bacteria and humans suggests that the structures may have an important function, says Dyche Mullins, a cell biologist at the University of California, San Francisco.

Cell biologists already knew that actin, one of the most important proteins for forming a cell’s skeletal structure, is closely related to another metabolically important enzyme called hexokinase. The assumption has been that actin started out as an enzyme but that its ability to build structures within the cell eventually became its primary function. The newly discovered filaments may be a snapshot of an enzyme in the process of taking on a new role as a structural protein, Mullins says. But because CTP synthase hasn’t fully made the transition to structural protein in billions of years of evolution, these filaments are probably as far as it will go. “It could be that CTP synthase is not as well suited to do multiple things as actin is,” Mullins says.

onishadowolf:
Cells reprogrammed to treat diabetes
Testes may be a source of insulin production
By Tina Hesman Saey
Web edition : Sunday, December 12th, 2010
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PHILADELPHIA — Sperm-forming stem cells in the testes can be converted to insulin-producing cells that could replace diseased ones in the pancreas, researchers from Georgetown University Medical Center in Washington, D.C., reported December 12 at the annual meeting of the American Society for Cell Biology. The new technique is edging closer to producing the amount of insulin needed to cure diabetes in humans.

Ian Gallicano, a developmental biologist at Georgetown, and his colleagues isolated sperm-producing stem cells from the testes of organ donors. These cells could easily revert to an embryonic state, capable of making nearly any cell in the body. The Georgetown researchers treated the cells with chemicals to coax them into mimicking beta-islet cells from the pancreas, the same kind of cells that are compromised in diabetes.

Reprogrammed sperm-producing cells cured diabetes in mice for about a week before their insulin levels dropped again. “If you’re a mouse and you have diabetes, you’re in good shape these days,” Gallicano says.
But cells need to make much more insulin in order to cure diabetes in humans. In islet cells in the human pancreas, insulin accounts for about 10 percent of the proteins secreted by the cell. No stem cell from the testes or anywhere else has come close to making that amount of insulin, Gallicano says. He and his colleagues have developed a new way of programming insulin-producing cells and are getting closer to the goal of creating islet-like cells in which insulin accounts for 1 to 10 percent of the proteins in the cells.

Although testes-derived stem cells would be useful only for men, Gallicano thinks the tricks he’s developing could be adapted to other stem cells that could help women with diabetes too.

onishadowolf:
RNA, obey
Researchers build genetic devices to program cell actions
By Tina Hesman Saey
December 18th, 2010; Vol.178 #13 (p. 13)
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Scientists are one step closer to learning how to program cells the way other people program computers.

Researchers led by Christina Smolke, a biochemical engineer at Stanford University, report the accomplishment in the Nov. 26 Science.

Smolke and her colleagues created RNA devices that could rewire cells to sense certain conditions and respond by making particular proteins. Such technology might be harnessed for creating cell-based therapies and cancer-fighting treatments. Someday, scientists might also be able to flip an RNA switch to make plants more tolerant to drought or coax yeast to produce industrial chemicals.

Other researchers have reported building RNA-programming components before, but Smolke’s group is the first to integrate all the pieces into a fully functional system, says Adam P. Arkin, a systems and synthetic biologist at Lawrence Berkeley National Laboratory and the University of California, Berkeley. “It’s sort of like building the first functional car,” says Arkin, who was not involved in the study. “Yeah, combustion was around and there were things that rolled, but actually putting them together” was the real breakthrough.

The new invention is based on eons-old genetic material, RNA molecules. Smolke and her team rigged up RNA molecules that work a bit like a security system that is tuned to be triggered by only one type of intruder. In this case, the RNA molecules detect particular proteins and then turn on or off production of another protein in response.

The team’s first device made human kidney cells glow with a fluorescent protein when the RNA detected a protein from a virus that infects bacteria. Then the researchers got fancier and configured the system so that the cells would kill themselves if the RNA program detected high levels of proteins involved in promoting cancer. These feats, and others, are described in the new study.

These simple programs are just examples of what researchers might be able to make cells do in the future, Smolke says. She envisions that such RNA devices might be used to program animal, plant and fungal cells to do a wide variety of tricks. And the technology could be configured so that multiple conditions need to be met before initiating a program — say, turning on a cholesterol-lowering drug in the liver only after a high-fat meal.

“My sense is that it’s not going to work for everything,” Smolke says, “but it’s going to work for a large subset of things.”

onishadowolf:
Big reveals for genome of tiny animal
Tunicates’ scrambled gene order suggests arrangement may not matter for vertebrate body plan and hints at origins of mysterious bits of DNA
By Tina Hesman Saey
December 18th, 2010; Vol.178 #13 (p. 13)
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UNSTRUCTUREDThe study of tunicates, the second most abundant type of zooplankton in the oceans, is helping to reveal where mysterious chunks of DNA called introns come from. The tiny, transparent organisms are made visible here by adding milk to seawater.Jean-Marie Bouquet and Jiri Slama, © Science/AAAS

As any devotee of Antiques Roadshow can tell you, just because something has been saved doesn’t mean it’s valuable.

Now, a study of plankton shows that a well-preserved genome isn’t necessarily responsible for how vertebrate animals, including humans, are put together. Researchers in Norway and France have deciphered the genetic blueprints of a tunicate called Oikopleura dioica, a tiny member of one of the most abundant plankton types in the oceans. The animal’s compact genome contains roughly 18,000 genes — nearly as many as the human genome’s 22,000 or so, but with genes in a completely different order and less DNA stuffed in between them, the researchers report online November 18 in Science.

The finding came as something of a surprise to researchers since it’s been thought that the arrangement of genes on chromosomes helps determine how an organism’s body plan will be laid out. Humans and other vertebrates tend to have genes arranged in similar order. So do organisms such as sponges. Many researchers thought that this genomic structure was important since it was preserved over millions of years of evolution. But the tunicate genome’s scrambled gene order could indicate that other organisms’ genomes got and stayed that way without any pressure from natural selection to maintain the structure.

“Intuitively, you wouldn’t believe that just by chance things would be conserved for 500 million years,” says Daniel Chourrout, a developmental and genome biologist at the Sars International Centre for Marine Molecular Biology at the University of Bergen in Norway and a coauthor of the new study. But the new evidence indicates that the common genome structure found in most animals may have been maintained simply due to inertia, or genetic drift, he says.

The tunicate genome contains a few other golden nuggets of information as well, including clues about how introns form. Introns are chunks of DNA that interrupt the protein-building instructions in genes and have been called “junk DNA,” although scientists have discovered that many introns also help regulate activity of the genes they interrupt. Others have no known function.

Most introns are so old that scientists have been unable to infer the introns’ origins. But of the 5,589 introns identified in the tunicate genome, 76 percent have not been seen before in studies of other organisms. Closer examination of the tunicate introns indicates that many are copied from other introns and then inserted into the genome in new places, much like other highly mobile bits of DNA known as jumping genes or transposable elements.

Other scientists have postulated that that’s how introns come about, but the new report is the first direct evidence, says Michael Lynch, an evolutionary biologist at Indiana University in Bloomington. “Still one of the big mysteries in evolutionary biology is where introns come from,” he says, “so any insight into that is welcome.”

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