From Unknown Bacteria To Biotechnology Breakthrough
Sep17

From Unknown Bacteria To Biotechnology Breakthrough

Today’s post is by Andrea Widener, a government and policy writer for C&EN and lover of obscure science. Microbiologist Tom Brock’s first forays into Yellowstone National Park to seek out life in its hot springs are just the kind of basic research that sometimes gets ridiculed by politicians. In an effort to end government waste, some of these public servants like to make examples out of federally funded research that seems irrelevant or that doesn’t have immediate applications. In the 1960s, when Brock hiked into Yellowstone, “we didn’t know there were organisms that could live in boiling water,” the microbiologist says. So he couldn’t have known he would find a heat-seeking bacterium that would become central to modern-day DNA technology. That discovery, funded by the National Science Foundation, earned Brock a Golden Goose Award last week. Here at Newscripts, we wrote about the original founding of the Golden Goose Awards last year. Other awards, like the Ig Nobel prizes given out last week (see Newscripts' coverage here), also seek out the obscure, but the goal of the Golden Goose is to point out the seemingly irrelevant, but federally funded, research that has gone on to make an important difference. “We’ve all read stories about the study with the wacky title, the research project from left field,” says Rep. Jim Cooper (D-Tenn.), who first proposed the awards. “But off-the-wall science yields medical miracles. We can’t abandon research funding only because we can’t predict how the next miracle will happen.” What Brock and undergraduate Hudson Freeze found in 1966 in Yellowstone’s Mushroom Spring was the bacteria Thermus aquaticus. The heat-loving bacteria produces an enzyme, Taq polymerase, that is now essential to polymerase chain reaction (PCR), a technique that amplifies DNA and is used in genome sequencing, forensics, and diagnosis of genetic disorders. “We were looking for a simple system where one could do basic research in microbial ecology. Everything fell out of that,” Brock says. But Brock’s basic research wasn’t the only one honored with a Golden Goose last week. Mathematicians Lloyd Shapley and David Gale, with economist Alvin Roth, were also recognized for their efforts to design a program that would make the perfect marriage match. The deferred choice algorithm, supported in 1962 by the Office of Naval Research, was designed by Gale and Shapley to maximize marriage stability, so that each man or woman was paired with the best possible mate. That seemingly frivolous area of study seems sure to draw Congressional ire today. But the theoretical application led to other matching programs that do important work. With funding from NSF, Roth designed a system that matches kidney recipients...

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Amusing News Aliquots
Mar14

Amusing News Aliquots

Silly samplings from this week's science news, compiled by Lauren Wolf. Today’s Pi Day! Celebrate by, um, tossing hotdogs down a hallway. [WikiHow] Harvard is making robot bees. Sigh. Hasn’t ANYONE watched “2001: A Space Odyssey,” or “iRobot”? Sure, robobees are super cool, but this isn’t going to end well. [iO9] DNA from fish (herring) sperm is a flame retardant, study shows. Hmmm … that’s going to be an interesting production/extraction process. [Wired] Smart people like curly fries. Straight men often do Internet searches for “Being confused after waking up from naps.” This, according to a study of Facebook by Cambridge University researchers. [NBC Bay Area] We thought that to bend the spoon with your mind, you have to realize that there is no spoon. What do we know? This guy says it has something to do with respiration. [Improbable Research] Pass the Juicy Fruit: People chewing gum focus longer on a task than those who aren’t. [iO9]...

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Amusing News Aliquots
Mar08

Amusing News Aliquots

Silly samplings from this week's science news. Compiled by Bethany Halford and Lauren Wolf. Why were dinosaurs so angry? Perhaps it was the giant fleas. [NY Times] Spiderwebs overtake town. Newscripts gang going home, locking door, and staying there. [iO9] Amateur astronomy group flashes space station … with a laser. Get your minds out of the gutter. [Air And Space Smithsonian] Same genes activated by exercise are activated by large doses of caffeine. We’d like eight espressos to go, please. [Gizmodo] Got water, salt, dish soap, alcohol, and food coloring? Then you can extract your own DNA. [NOVA on YouTube] Think your favorite watering hole is swapping your Coke for discount cola? Just take a sample to the NMR to find out. [J. Ag. Food Chem.] Thinking of splurging on a $90 bottle of wine? Scientists say you’re probably wasting your money. [NPR]...

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Ensemble Hits Macrocycle Milestone
Apr12

Ensemble Hits Macrocycle Milestone

Today, Ensemble Therapeutics announced it has developed experimental drugs with molecular structures containing a large ring, which the company calls Ensemblins, against one of 8 key drug targets laid out in a 2009 agreement with Bristol-Myers Squibb Company (BMS). As a result, the drug development program will be handed off to BMS and Ensemble will receive a milestone payment. Neither the drug target nor the milestone payment amount have been disclosed. I first became acquainted with Ensemble in 2008, when I wrote about a symposium extolling the potential benefits of compounds containing rings of 12 or more atoms, also known as macrocycles, in drug discovery. These molecules are larger in size than traditional small molecule drugs, but they can increase the strength of a binding interaction at a desired target, or even make it possible to target proteins in the body that traditional small molecule drugs can't. Some macrocylic drugs are already on the market, such as the antibiotic erythromycin and the immunosuppressant rapamycin. In 2009, I focused on one of Ensemble's proprietary drug discovery programs, but since then the company has partnered with both Pfizer and BMS, developing macrocyclic Ensemblins for tough-to-hit targets. In reporting the 2009 story, I learned that Ensemble's discovery platform, which is based on chemistry carried out in company founder David R. Liu's lab at Harvard University, uses DNA to guide production of thousands of different macrocycles at a time, and then tests the macrocycles' ability to disrupt biologically relevant interactions between proteins. Drugmakers tend to develop biologic drugs to tackle these so-called protein-protein interactions, because these interactions don't usually have the kind of well-defined pockets a small molecule can wedge its way into- they come together more like two marshmallows as opposed to two LEGO bricks. Given that knowledge I asked medicinal chemist Michael D. Taylor, Ensemble's president and CEO, about the nature of the 8 key targets in the BMS collaboration. "Macrocycles are useful for a variety of different targets," Taylor says. "We've always thought that protein-protein interactions are an area or particular importance and our partners have emphasized protein-protein interactions within the collaborations that we have, so it's fair to say that the vast majority of the targets fall in that area." Ensemble's press release about the milestone also mentions that the company has made improvements to its platform to boost output as well as druglike qualities in its libraries of macrocycles. I asked Ensemble's chief scientific officer Nick K. Terrett, also a medicinal chemist, to elaborate. He says the changes come in two areas- first, to the company's DNA-guided discovery platform, and second, to the organic chemistry used to make...

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