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Title: Scientists Map Elusive 3-D Structure of Telomerase Enzyme, Key Actor in Cancer, Aging
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URL Source: http://www.sciencedaily.com/releases/2013/04/130412132430.htm
Published: Apr 13, 2013
Author: staff
Post Date: 2013-04-13 04:24:25 by Tatarewicz
Keywords: None
Views: 58
Comments: 4
Apr. 11, 2013 — Like finally seeing all the gears of a watch and how they work together, researchers from UCLA and UC Berkeley have, for the first time ever, solved the puzzle of how the various components of an entire telomerase enzyme complex fit together and function in a three-dimensional structure. The creation of the first complete visual map of the telomerase enzyme, which is known to play a significant role in aging and most cancers, represents a breakthrough that could open up a host of new approaches to fighting disease, the researchers said. "Everyone in the field wants to know what telomerase looks like, and there it was. I was so excited, I could hardly breathe," said Juli Feigon, a UCLA professor of chemistry and biochemistry and a senior author of the study. "We were the first to see it." The scientists report the positions of each component of the enzyme relative to one another and the complete organization of the enzyme's active site. In addition, they demonstrate how the different components contribute to the enzyme's activity, uniquely correlating structure with biochemical function. The research appears April 11 in the print edition of the journal Nature. "We combined every single possible method we could get our hands on to solve this structure and used cutting-edge technological advances," said co-first author Jiansen Jiang, a researcher who works with Feigon and the study's co-senior author, Z. Hong Zhou, director of the Electron Imaging Center for Nanomachines at the California NanoSystems Institute at UCLA and a professor of microbiology, immunology and molecular genetics. "This breakthrough would not have been possible five years ago." "We really had to figure out how everything fit together, like a puzzle," said co-first author Edward Miracco, a National Institutes of Health postdoctoral fellow in Feigon's laboratory. "When we started fitting in the high-resolution structures to the blob that emerged from electron microscopy, we realized that everything was fitting in and made sense with decades of past biochemistry research. The project just blossomed, and the blob became a masterpiece." The telomerase enzyme is a mixture of components that unite inside our cells to maintain the protective regions at the ends of our chromosomes, which are called telomeres. Telomeres act like the plastic tips at the end of shoelaces, safeguarding important genetic information. But each time a cell divides, these telomeres shorten, like the slow-burning fuse of a time bomb. Eventually, the telomeres erode to a point that is no longer tolerable for cells, triggering the cell death that is a normal part of the aging process. While most cells have relatively low levels of telomerase, 80 percent to 90 percent of cancer cells have abnormally high telomerase activity. This prevents telomeres from shortening and extends the life of these tumorigenic cells -- a significant contributor to cancer progression. The new discovery creates tremendous potential for pharmaceutical development that takes into account the way a drug and target molecule might interact, given the shape and chemistry of each component. Until now, designing a cancer-fighting drug that targeted telomerase was much like shooting an arrow to hit a bulls-eye while wearing a blindfold. With this complete visual map, the researchers are starting to remove that blindfold. "Inhibiting telomerase won't hurt most healthy cells but is predicted to slow down the progression of a broad range of cancers," said Miracco. "Our structure can be used to guide targeted drug development to inhibit telomerase, and the model system we used may also be useful to screen candidate drugs for cancer therapy." The researchers solved the structure of telomerase in Tetrahymena thermophila, the single-celled eukaryotic organism in which scientists first identified telomerase and telomeres, leading to the 2009 Nobel Prize in medicine or physiology. Research on Tetrahymena telomerase in the lab of co-senior author Kathleen Collins, a professor of molecular and cell biology at UC Berkeley, laid the genetic and biochemical groundwork for the structure to be solved. "The success of this project was absolutely dependent on the collaboration among our research groups," said Feigon. "At every step of this project, there were difficulties," she added. "We had so many technical hurdles to overcome, both in the electron microscopy and the biochemistry. Pretty much every problem we could have, we had, and yet at each stage these hurdles were overcome in an innovative way." One of the biggest surprises, the researchers said, was the role of the protein p50, which acts as a hinge in Tetrahymena telomerase to allow dynamic movement within the complex; p50 was found to be an essential player in the enzyme's activity and in the recruitment of other proteins to join the complex. "The beauty of this structure is that it opens up a whole new world of questions for us to answer," Feigon said. "The exact mechanism of how this complex interacts with the telomere is an active area of future research." "The atmosphere and collaboration at UCLA really amazes me, and that is combined with some of the most advanced facilities around," Zhou said. "We have a highly advanced electron microscopy facility here at UCLA that even researchers without a strong background in electron microscopy can learn how to use and benefit from. This will be really useful as we move forward." This research was funded by the National Science Foundation and the National Institutes of Health. Equal contributions to the publication were made by co-first authors Jiang and Miracco, postdoctoral researchers at UCLA with Zhou and Feigon. Members of Kathleen Collins' UC Berkeley laboratory who contributed to this research included technician Kyungah Hong, postdoctoral researcher Barbara Eckert and former graduate researcher Bosun Min. Other co-authors included Henry Chan and Darian D. Cash, UCLA graduate student researchers in Feigon's laboratory.
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#1. To: Tatarewicz (#0)
well that is a scary development. I think it means immortality. __ There are only two kinds of americans left in the USA those opposed to the tyranny and those that are wrong. Resist propaganda, Support strict constitutional adherence!
Someone was advertising Isagenix, a multi level marketing nutrition company at a Ron Paul site. There are tons of those nutrition companies, but after digging a bit Isagenix offers a Telomere product-which no one else does (TMK) yet anyway. I was tempted to join just to buy and use this Telomere product, but when I asked a one DOUG WEAD if it was possible to only buy and sell the Telomere product, I never got an answer back. Still going to pursue it- but won't be in Wead's down line. After watching Wead "perform" in Paul's campaign, not sure how trustworthy he is anyway. This is an interesting article about the guy that invented that Telomere product: The Man Who Would Stop Time Bill Andrews has spent two decades unlocking the molecular mechanisms of aging. His mission: to extend the human life span to 150 years--or die trying Bill Andrews’s feet are so large, he tells me, that back when he was 20 he was able to break the Southern California barefoot-waterskiing distance record the first time he put skin to water. Then he got ambitious and went for the world speed record. When the towrope broke at 80 mph, he says, “they pulled me out of the water on a stretcher.” The soles of the size-15 New Balances that today shelter those impressive feet strike a steady clap-clap on the macadam as Andrews and I lope down a path along the Truckee River that takes us away from the clutter of cut-rate casino hotels, strip malls and highway exit ramps that is downtown Reno, Nevada. Andrews, 59, is a lean 6-foot-3 and wears a close-cropped salt-and-pepper Vandyke and, for today’s outing, a silver running jacket, nicely completing a package that suggests a Right Stuff–era astronaut. He is in fact one of the better ultramarathoners in America. I am an out-of-shape former occasional runner, so it gives me pause to listen as Andrews describes his racing exploits. “I can run 100 miles, finish, turn around, and meet friends of mine on the course who are still coming in,” he says. “I’ve been in many races where I’m stepping over bodies of people who have collapsed, and I’m feeling great.” His return to running after a middle-aged break was, he says, inspired by a revelation he had at a time when he and a small team of scientists at his biotech start-up, Sierra Sciences, had been working 14 to 18 hours a day in the lab for five years, rather obsessively pursuing a particular breakthrough. Finally, his doctor told him he was headed for an early grave. “I thought, god, I don’t want to cure aging and then drop dead,” Andrews says. That would indeed be ironic. Because Andrews does intend to cure aging. This stated ambition induces in some listeners the suspicion that Andrews might suffer from delusions of grandeur, but he has a scientific pedigree that insists he be taken seriously. Unlike his friend Aubrey de Grey, the University of Cambridge longevity theorist who relentlessly generates media attention with speculations that straddle the border between science and science fiction, Andrews is an actual research scientist, a top-drawer molecular biologist. In the 1990s, as the director of molecular biology at the Bay Area biotech firm Geron, Andrews helped lead a team of researchers that, in alliance with a lab at the University of Colorado, just barely beat out the Massachusetts Institute of Technology in a furious, near-decade-long race to identify the human telomerase gene. That this basic science took on the trappings of a frenzied Great Race is a testament to the biological preciousness of telomerase, an enzyme that maintains the ends of our cells’ chromosomes, called telomeres. Telomeres get shorter each time a cell divides, and when they get too short the cell can no longer make fresh copies of itself. If we live long enough, the tissues and organ systems that depend on continued cell replication begin to falter: The skin sags, the internal organs grow slack, the immune-system response weakens such that the next chest cold could be our last. But what if we could induce our bodies to express more telomerase? We’ll see, because that is what Andrews intends to do. Andrews had scheduled this afternoon’s run as an 18-miler, but he graciously downscaled those ambitions on my behalf long before we set out from the parking lot of the Grand Sierra Resort Hotel. Four miles in, he’s hardly winded—and I’m out of gas. As we make our way back to his car, he consults his training watch and informs me that our pace was an almost respectable 8:40, excepting the latter stretches when I walked, pushing our average up to 10 minutes a mile. The embrace of fitness has for Andrews a telomeric logic. Make poor lifestyle choices, and you’re likely to die of heart disease or cancer or something well before your telomeres would otherwise become life-threateningly short. But for the aerobicized Andrews, for anyone who takes reasonable care of himself, a drug that activates telomerase might slow down the baseline rate at which the body falls apart. Andrews likens the underlying causes of aging, free radicals and the rest, to sticks of dynamite, with truncated telomeres being the stick with the shortest fuse. “I believe there’s a really good chance that if we defuse that stick,” he says, “and the person doesn’t smoke and doesn’t get obese, it wouldn’t be surprising if they lived to be 150 years old. That means they’re going to have 50 more years to be around when somebody solves the other aging problems.” But in his race to cure aging, Andrews may himself be running out of time. The stock-market crash of 2008 nearly wiped out two investors who had until then been his primary funders. Without the money to continue refining the nearly 40 telomerase-activating chemicals he and his team had already discovered, Andrews made the decision last September to cut a deal with John W. Anderson, the founder of Isagenix, an Arizona-based “network marketing” supplement company. This month, Isagenix will launch an anti-aging product containing several natural compounds that Sierra Sciences has verified to have “telomere-supporting” properties. It’s not the powerful drug Andrews originally envisioned, but he says he believes it will promote “health and well-being” and just possibly generate enough cash to underwrite the expensive “medicinal chemistry” required to come up with a more fully developed anti-aging compound—one attractive enough to bring in a billionaire or a Big Pharma partner with pockets deep enough to take a drug candidate through the FDA’s time-consuming and fabulously expensive approval process. “I want to cure my aging,” Andrews tells me, “my friends’ and family’s aging, my investors’ aging, their friends’ and families’ aging, and make a ton of money. And I want to cure everybody else’s aging too—I put that probably equal to making a ton of money." 5 more pages (and well worth the time): Even without Telomeres type products look at what is possible just by eating right:
Fascinating - thanks.
“The most dangerous man to any government is the man who is able to think things out... without regard to the prevailing superstitions and taboos. Almost inevitably he comes to the conclusion that the government he lives under is dishonest, insane, intolerable.” ~ H. L. Mencken "Fighting disease" or spreading disease? Admittedly, I'm more than a little jaded but when I see research, such as this, funded by two government agencies, I get more than slightly concerned about the actual motives. “I believe that there will ultimately be a clash between the oppressed and those who do the oppressing. I believe that there will be a clash between those who want freedom, justice, and equality for everyone and those who want to continue the system of exploitation. I believe that there will be that kind of clash, but I don’t think it will be based on the color of the skin…” -Malcolm X
#2. To: Tatarewicz (#0)
By Joseph Hooper Posted 08.02.2011 Popular Science 
http://www.popsci.com/science/article/2011-07/man-who-would-stop-time
http://www.youtube.com/watch?v=VdeC3OJJIzA
#3. To: Aquila (#2)
#4. To: Tatarewicz (#0)
The creation of the first complete visual map of the telomerase enzyme, which is known to play a significant role in aging and most cancers, represents a breakthrough that could open up a host of new approaches to fighting disease, the researchers said.
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