University of Wisconsin-Madison biochemistry professor <a href="http://www.biochem.wisc.edu/faculty/holden/default.aspx">Hazel Holden</a> and Edgewood Campus School middle-school science teacher Daniel Toomey met for the first time because Holden's daughter was in Toomey's science class. Neither anticipated that less than three years after their first encounter at the Madison school, they'd be working closely to bridge the gap between middle-school science and groundbreaking research, and to get young adolescents excited about chemistry before high school. "We just thought we've got to teach chemistry at an earlier age, and we've got to make it exciting," Holden says. "By the time you get to high school, you've kind of set the path for what you want to do." Realizing the unusual potential a partnership between a middle-school science teacher and a biochemistry researcher would have for both the teenagers and Holden's lab, the two teamed up to form <a href="http://www.projectcrystal.org/">Project CRYSTAL</a> (Crystallographers Researching with Young Scientists: Teaching And Learning). The duo was awarded a grant from the National Science Foundation (NSF) last April to bring six students from Edgewood Campus School to research X-ray crystallography alongside graduate students in Holden's lab. Six carefully selected students began their research at the beginning of the 2009-10 school year. They make the trip to the UW-Madison campus once a week to assist Holden and the graduate students in real-world research. It gives young students an opportunity to learn that the world of science extends far beyond textbook experiments. "A lot of what we do as science educators in K-12 is pretty much the cookbook labs where you know the results, and that's not science," Toomey says. "What the kids are realizing is you have to observe, and you wait for your results, and they're probably not what you expected. I think that's the beauty of this for them, that they get a chance to realize that there's not always a clear-cut answer." Project CRYSTAL also gives graduate students a unique teaching opportunity. "TA-ing the basic chemistry class with undergrads is completely different than trying to teach them," says biochemistry graduate student Amanda Carney. "It's an interesting way to try to think about things from a completely different perspective." Holden adds that the teaching assistants serve as role models for the students, since they are closer in age than most of their traditional teachers. "It's interesting to see what people actually do," says seventh-grader Manpreet Kaur. "I've always liked science, but I think it gives me a little bit more knowledge, and I'm definitely more into it than I was before." Every week, the six students blog about their experiences in the lab at http://www.projectcrystal.org/crystallographers-researching-with-young-scientists-4/project-crystal-blog Because Holden's lab only has room for six middle-schoolers, Toomey and Holden looked for ways to expose the rest of his students to chemistry. In the NSF grant, the pair noted they would develop modules to teach a chemistry unit to Toomey's seventh- and eighth-graders. The module includes an analogy comparing ice cream flavors to the periodic table, an introduction to the structure of molecules, compounds and atoms, and most notably, the chemistry of sugars and carbohydrates. "My motivation was just seeing kids drink a lot of energy drinks and soda after soda," Toomey says. "We want to educate kids about making healthy choices so that when they're in whatever setting they're in, they'll use their chemistry knowledge to make healthy choices." Toomey and Holden intend to have chemistry of sugars modules on the Web by the end of the month for other middle-school teachers to use in their classrooms. The final component of the NSF grant is community outreach. Through personal connections, Toomey was able to hook up with former UW-Madison basketball star and NBA All-Star player Devin Harris, who hosts an annual basketball camp for underprivileged youth in Milwaukee. Harris, who infuses education with sports at his camp, invited Toomey and a few UW-Madison biochemistry graduate students to teach at the camp for a day. Last August, Toomey and the graduate students made the trip to Milwaukee and taught 360 kids ages 7-15 about the chemistry of sugar and its nutritional ramifications. They conducted experiments and handed out posters to remind the students of the high sugar content in soda and energy drinks. Toomey, who plans to return to teach at Harris's camp annually, extended his collaboration with Harris to include a "Learn with Devin Harris" segment on the Project CRYSTAL <a href="http://www.projectcrystal.org/">Web site</a>. The segment teaches science in the context of sports. The current segment challenges kids to calculate Harris's speed in an on-court video clip. Toomey and Holden continue to collaborate with the Devin Harris Foundation — 34 Ways to Assist — to seek additional outreach opportunities. University of Wisconsin-Madison biochemistry professor Hazel Holden and Edgewood Campus School middle-school science teacher Daniel Toomey met for the first time because Holden's daughter was in Toomey's science class. Project CRYSTAL brings middle-school students to UW-Madison lab 17268 2009-10-22T09:16:00-05:00

15595

2009-10-22T09:16:18-05:00

While at the University of Wisconsin-Madison, biochemist Har Gobind Khorana helped crack the genetic code, completing a set of experiments that garnered him a Nobel Prize in 1968. Shortly thereafter, he went on to synthesize the first artificial gene. Today, science has advanced to the point where entire genomes — the genetic blueprints for living organisms — can be assembled from scratch. Later this month, the UW-Madison <a href="http://www.biochem.wisc.edu/">Department of Biochemistry</a> will host a symposium in honor of Khorana, titled "<a href="http://steenbock33.biochem.wisc.edu">Synthetic Genes to Synthetic Life: On the Exploration and Synthesis of Biological Systems</a>," that is designed to highlight the significance and legacy of his groundbreaking work. The speaker roster includes numerous rock star-caliber scientists, including Khorana, three other Nobel laureates, recipients of the Lasker Award (the "American Nobel") and the National Medal of Science, and many others. "In less than 50 years, we've come such a long way, from being able to synthesize little pieces of DNA to being able to synthesize life," says biochemist Aseem Ansari, the symposium's head organizer. "Building life is the holy grail. From simple chemicals, can scientists build something that lives, evolves?" During the four-day symposium, which runs from Thursday, July 30-Sunday, Aug. 2, more than 50 researchers will talk about the key scientific advances — starting with Khorana's work — that have made it possible to re-engineer cells and create life from scratch. The latter work will be the topic of a session titled "Origins and Designing Life-Synthetic Life," set for 4:45-6:25 p.m. on Saturday, Aug. 1. All sessions will take place at campus's Ebling Symposium Center in the Microbial Sciences Building, 1550 Linden Drive. Although full registration costs $215, there will be a room set up where interested parties can watch the symposium for free via live video feed, and ask questions during question-and-answer exchanges. Parking is available in Lot 20, at 1400 University Ave., and Lot 17, at 1525 Engineering Drive. Parking is free on weekends and after 4:30 p.m. on weekdays. While at the University of Wisconsin-Madison, biochemist Har Gobind Khorana helped crack the genetic code, completing a set of experiments that garnered him a Nobel Prize in 1968. UW-Madison symposium addresses science's holiest grail: building life from scratch 16918 2009-07-23T08:58:00-05:00

15412

2009-07-23T08:59:10-05:00

A fundamental question about how sugar units are strung together into long carbohydrate chains has also pinpointed a promising way to target new medicines against tuberculosis. Working with components of the tuberculosis bacterium, researchers from the University of Wisconsin-Madison identified an unusual process by which the pathogen builds an important structural carbohydrate. In addition to its implications for human health, the mechanism offers insight into a widespread but poorly understood basic biological function — controlling the length of carbohydrate polymers. "Carbohydrate polymers are the most abundant organic molecules on the planet, and it's amazing that we don't know more about these are made," says <a href="http://www.biochem.wisc.edu/faculty/kiessling/">Laura Kiessling</a>, a professor of chemistry and biochemistry at UW-Madison. "There's not much known about how length is controlled in these carbohydrate polymers." Kiessling is senior author, along with graduate students John May and Rebecca Splain and postdoctoral fellow Christine Brotschi, of a new study appearing in the online Early Edition of the Proceedings of the National Academy of Sciences the week of June 22. Most carbohydrates exist as many sugar molecules linked into long chains, or polymers. The right number of sugars in the chain is vital for them to work properly, but different types of carbohydrate polymers range from a few dozen sugars in some bacterial molecules to tens of thousands of sugar links in cellulose, a common plant material. Despite its importance, it's not clear how carbohydrate length is determined, Kiessling says. Unlike some biological chains — such as DNA and proteins — that are built off a template that guides the length of the final product, carbohydrate-synthesizing enzymes work without templates. "Nature has strategies to generate polymers of different lengths, but we know very little about those strategies," she says. "If you make something too short, it's probably not going to function in the role that you want, and if you make something too long, you're wasting energy that you need to use elsewhere." The research team focused on an enzyme called GlfT2 that is responsible for building a critical carbohydrate component of the TB bacterial cell wall. The researchers found that a small fatty component at the starting end binds to the enzyme and helps it track the length of the growing polymer. As the enzyme adds more and more sugar units to the opposite end, the chain becomes increasingly unwieldy. "If the chain gets too long, it gets hard to hold on to both of the ends, so the chain falls off" the synthesizing enzyme, Kiessling says, forming a completed carbohydrate polymer. The researchers believe that the enzymes responsible for building different types of carbohydrates exceed their comfort level at different points, leading to molecules of different prescribed lengths. The current report is the first description of this "tethering" mechanism — named for the fatty lipid that tethers the start of the polymer to the enzyme — in carbohydrate synthesis, Kiessling says, though it may prove to be common among other organisms as well. In addition to providing insight into what may be a general mechanism for designing and building carbohydrates, the work gives insight into developing new therapeutics against TB. The GlfT2 enzyme is essential for bacterial survival and growth but has never yet been targeted by potential treatment methods. Knowing that the enzyme has two binding sites — one for each end of the growing carbohydrate — makes it an especially appealing candidate. "Our mechanism provides a blueprint for strategies to block a new anti-mycobacterial target," Kiessling says. New drug targets will be critical in the fight against tuberculosis, as drug-resistant strains are becoming increasingly widespread. The carbohydrate-synthesizing enzyme represents an untapped and promising resource for crippling even strains that are resistant to current drugs. The prevalence of carbohydrate polymers in biological systems also means that understanding how their length is controlled has many possible applications, ranging from designing more potent and effective vaccines to facilitating the production of useful fuels from plant materials. "It's a nice illustration of how basic research can lead to applications that are very practical," says Kiessling. The research was funded by the National Institutes of Health, National Science Foundation, American Chemical Society and Swiss National Science Foundation. A fundamental question about how sugar units are strung together into long carbohydrate chains has also pinpointed a promising way to target new medicines against tuberculosis. Carb synthesis sheds light on promising tuberculosis drug target 16845 2009-06-22T16:24:00-05:00

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2009-06-22T19:25:04-05:00

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Two members of the University of Wisconsin-Madison faculty are among 72 scientists from around the world who have been elected fellows of the American Academy of Microbiology. Elected as fellows are <a href="http://www.biochem.wisc.edu/faculty/palmenberg/">Ann Palmenberg</a>, a virologist and UW-Madison professor of biochemistry, and <a href="http://www.biochem.wisc.edu/faculty/record/">M. Thomas Record</a>, a UW-Madison professor of chemistry and biochemistry. Also elected was <a href="http://www.biochem.wisc.edu/faculty/reznikoff/">William Reznikoff</a>, a professor emeritus of biochemistry who is now at the Woods Hole Oceanographic Institution. American Academy of Microbiology fellows are elected annually through a highly selective peer-review process. Election is based on scientific achievement and a record of original contribution that has advanced the field. Two members of the University of Wisconsin-Madison faculty are among 72 scientists from around the world who have been elected fellows of the American Academy of Microbiology. UW faculty recognized by American Academy of Microbiology 16318 2009-02-23T12:03:00-06:00

15085

2009-02-25T12:50:19-06:00

A proposal to create a stealth drug, one that remains cloaked inside a cell until activated by a pathogen, has snared a high-profile $100,000 award from the <a href="http://www.gatesfoundation.org/Pages/home.aspx">Bill & Melinda Gates Foundation</a>. UW-Madison biochemist <a href="http://www.biochem.wisc.edu/faculty/raines/">Ron Raines</a>' proposal to the Gates Foundation's Grand Challenges in Global Health initiative beat 40-to-1 funding odds and is aimed broadly at developing therapeutic agents that limit drug resistance. The idea floated by Raines and his group involves creating a novel cytotoxin, an agent poisonous to cells, from an enzyme known as a ribonuclease whose job is to cleave RNA. By making an inactive precursor form of the RNA-slicing enzyme, Raines says, it's possible to deliver the agent to cells where it can reside benignly until activated by a pathogen such as HIV. In the case of HIV infection, the cloak, Raines explains, is removable only by a protein-slicing enzyme that the pathogen requires to complete its life cycle. "As that cleavage can only occur in cells infected with the HIV-1 virus, the toxic activity of the ribonuclease will be unleashed only in infected cells." A therapy that kills only HIV-infected cells has the potential to eradicate in patients the reservoir where the virus does its dirty work. The strategy, Raines adds, could also be used as a prophylactic, preventing the virus from getting a foothold in the cells it commandeers to make new virus particles. The approach, according to Raines, could also be used to develop strategies for combating pathogens in addition to HIV. A proposal to create a stealth drug, one that remains cloaked inside a cell until activated by a pathogen, has snared a high-profile $100,000 award from the Bill & Melinda Gates Foundation. Stealth drug idea snags Gates Foundation support 15945 2008-11-12T10:20:00-06:00

14907

Scientists are probing the complex relationship between our DNA and our diets to unravel the root causes of obesity. But for those seeking a simple solution to the worldwide fat epidemic, their answers may be hard to swallow. http://www.news.wisc.edu/features/the-biology-of-obesity/ The biology of obesity: Do these genes make me look fat? 15487 2008-08-15T00:00:00-05:00

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Already home to one of the world's most impressive collections of huge research instruments, the University of Wisconsin-Madison's <a href="http://www.nmrfam.wisc.edu/">National Magnetic Resonance Facility at Madison</a> (NMRFAM) is about to add another giant. Located deep within the biochemistry addition at UW-Madison, the facility houses a number of high-tech machines called NMR spectrometers, which use a magnet and radio waves to reveal the structures and dynamic properties of molecules in fine detail. The most powerful of these machines — which can be up to a story tall and cost as much as $5 million — are too large and expensive for ordinary labs to own, and UW-Madison's NMR lab is used regularly by academic and industry researchers working at the leading edge of medicine and biological research. Now, those capacities are set to expand. The <a href="http://www.ncrr.nih.gov/">National Center for Research Resources</a>, a branch of the National Institutes of Health, announced today (July 17) that UW-Madison is among 20 U.S. universities that will receive grants to purchase the tools they need to stay at the forefront of biology and medicine. UW-Madison's grant, totaling more than $1.6 million, will be used to purchase a high-end instrument that integrates a mass spectrometer, a nuclear magnetic resonance spectrometer and a liquid-chromatography system. The NMRFAM will become the first academic facility to house an instrument combining these three technologies, which is expected to benefit a wide variety of research projects, including the search for new antibiotics and drugs and the quest to identify new metabolic pathways. According to NMRFAM head John Markley, research conducted in the facility addresses a range of human diseases, such as cancer, tuberculosis, diabetes and polycystic ovary syndrome. He says the new technology will speed up the facility's work and open new frontiers for some of biology's most far-reaching work. Already home to one of the world's most impressive collections of huge research instruments, the University of Wisconsin-Madison's National Magnetic Resonance Facility at Madison (NMRFAM) is about to add another giant. Facility to house new instrument to speed biomedical research 15396 2008-07-17T00:00:00-05:00

14617

Most scientists can't help but daydream about their research projects, which is why you'll often find John Ralph doodling on restaurant napkins. The University of Wisconsin-Madison professor of biochemistry often interrupts his meals with a quick sketch, usually depicting some piece of the structure of lignin, the subject of his research for the past 36 years. But amid deepening concern over the world's dependency on oil, Ralph's napkin art might turn out to be as valuable as a rare Rembrandt. Lignin — a tough, glue-like substance that keeps plant cell walls from falling apart — presently stands as one of the chief barriers to making fuel from grasses and woody plants, which most experts see as a preferable alternative to ethanol made from corn kernels or other food sources. And few people in the world know more about lignin than Ralph, who until earlier this year was a scientist with the U.S. Dairy Forage Research Center at UW-Madison. During the past year, the affable New Zealander has been the subject of an intense bidding war among the three bioenergy research centers created last year by the U.S. Department of Energy, including UW-Madison's <a href="http://www.news.wisc.edu/bioenergy/">Great Lakes Bioenergy Research Center</a> (<abbr title="Great Lakes Bioenergy Research Center">GLBRC</abbr>). Ralph recently accepted an offer to join the GLBRC team, which means he'll now work full-time on achieving the holy grail of plant-based fuel. UW-Madison is betting that Ralph's intricate knowledge of plant cell walls will expose new ways of engineering plants that are easier to convert into ethanol. Although the technology already exists to do that, the process is energy-intensive and inefficient, which is why so-called "grassoline" has yet to emerge as a viable alternative to petroleum-based fuels or ethanol made from corn kernels. A major problem is that the two types of energy-rich components found in biomass — cellulose and hemicellulose — tend to get tangled up in a sticky web of lignin during processing. What is needed, and what Ralph is pursuing, is an easy way to remove lignin so that these long chains of sugars can be extracted from biomass, turned into simple sugars and converted to ethanol. "We are (developing the technology) to redesign an agricultural plant so that its lignin falls apart easier to make the production of ethanol much more efficient," says Ralph. "If we get this figured out, there is the potential for a huge reduction in the cost of ethanol." Ralph has been studying the chemistry of plant cell walls since he was 18, when he took a forest-service internship in his native New Zealand. He joined the federally funded <a href="http://ars.usda.gov/main/site_main.htm?modecode=36553000">Dairy Forage Research Center</a> in 1988, which also gave him an unpaid teaching and research appointment in UW-Madison's forestry department. For the next two decades, his group gradually perfected techniques for visualizing the components of plant cell walls using nuclear magnetic resonance spectroscopy (NMR), which allows scientists to determine the structure of chemicals in fine detail. "You need to know the structure of the plant cell wall so you can figure out how to break it down, what it's doing in various processing treatments and which treatments are effective or not," explains Ralph. A breakthrough from Ralph's group, which was announced last year, has reduced the time it takes to analyze plant samples from one month to less than a day, and is expected to speed the process of testing and engineering plants with faster-degrading lignin. It also turned Ralph's group — a three-person team that includes scientists Fachuang Lu and Hoon Kim — into a coveted asset: Within months of announcing the new method, the trio was being actively recruited by various institutes including the DOE-funded centers located in Berkeley, Calif., and Oak Ridge, Tenn. Because Ralph's previous appointment was funded by the U.S. Department of Agriculture, he was technically ineligible to work with UW-Madison's own bioenergy group, the GLBRC. But administrators in the College of Agricultural and Life Sciences quickly assembled a counteroffer that included a faculty position in the biochemistry department, allowing him to participate in GLBRC-sponsored research, which Ralph says was a significant factor in deciding to stay. "People with John's training, experience and creativity just do not exist in this country or elsewhere in the world," says Tim Donohue, GLBRC director and professor of bacteriology at UW-Madison. "It was critical to get John's research team plugged into the Wisconsin bioenergy effort. One only need look at the number and type of offers he was getting at other places to see his unique talents in chemistry and plant biology. By keeping John as a member of the Madison bioenergy research community, the campus, state, region and Great Lakes Center are positioned to maintain leadership in the emerging field of cellulosic biofuels." Ralph likes how the GLBRC "has brought together a lot of researchers who have never worked together before." And now that he's one of those researchers, he is continuing to develop and perfect ways to deal with lignin in the bioconversion process. He plans to keep working on a promising project that he and his former colleagues at the Dairy Forage Research Center hit upon: a way to alter lignin so that it "unzips" under mild processing conditions. "Plants need lignin, so the idea is to let the plants make lignin," says Ralph. "But (let them) make it the way we want it, not the way they usually make it." In the lab, the idea works. The group's altered lignin allows the plant biomass to release up to 70 percent more fiber — cellulose and hemicellulose — than with regular lignin, and it does so at lower temperatures. The group is currently collaborating with a South Carolina biotechnology company called ArborGen to create trees with this type of alteration, in the hopes that these fast-growing trees will become the major feedstock for a new and better biofuel. A UW-Madison biochemistry professor will stay at the university to join its Great Lakes Bioenergy Research Center. Lignin expert chooses to pursue biofuels research at UW-Madison 15359 2008-07-01T00:00:00-05:00

14586

University of Wisconsin-Madison biochemist <a href="http://www.biochem.wisc.edu/faculty/weibel/">Doug Weibel</a> may not be able to bend or shape cells any way he wants to — yet. However, Weibel's efforts to uncover the molecular choreography within the cell that governs their physical, chemical and physiological attributes — including shape, behavior and development — have earned the young scientist a prestigious <a href="http://www.searlescholars.net/">Searle Scholar Award</a>. The $300,000 award over three years was last conferred on a UW-Madison faculty member in 1997 when pharmacy professor Ben Shen was recognized. <div id="story_image_661" class="inline-content photo right" style="width: 200px"> <a href="http://www.news.wisc.edu/video/ecoli/index.html"><img src="http://www.news.wisc.edu/story_images/0000/0661/ecoli-movie-still.jpg" alt="Still frame from a movie showing swarming behavior in e. coli" /></a> <a href="http://www.news.wisc.edu/video/ecoli/index.html">View a Quicktime movie</a> showing a population of swarming cells of Escherichia coli on an agar surface. </div> The award will support Weibel's exploration of some of the fundamental mysteries of bacterial cells, work that promises to make them more amenable for study and manipulation in the interest of such things as the development of biofuels and new antibiotics. "We work specifically on bacteria," says Weibel, who joined the UW-Madison faculty in 2006. "One of the things we're really interested in is how bacteria sense their environment. For example, how can a cell sense if it's on a surface or in a liquid?" How cells respond to their environments, Weibel explains, is a complex mix of physical and chemical variables, and in the case of bacteria, those variables may vary from organism to organism. One critical problem Weibel's group is addressing is why it is so difficult to tame most bacteria, making it impossible for many important microorganisms to be studied in the lab. It is widely believed that more than 99 percent of the world's microbes can't be isolated and cultured using current methods. Weibel's approach to the problem, which is interdisciplinary in the extreme and weaves chemistry, material science and engineering into the equation, involves developing new polymer structures that mimic the natural habitats of different classes of bacteria. By designing microenvironments in tune with different kinds of bacteria, it may be possible to bring them within reach of science, affording better opportunities to thwart pathogenic microbes or tame those that might be useful for converting biomass to sugars that can be used in biofuels. Another thrust of the Weibel lab is helping to figure out why bacteria behave as they do. For example, is there such a thing as collective behavior in bacteria? "We're very interested in the question of how does collective behavior in populations of bacteria arise," Weibel says. "Emerging behavior is a property of a system you can't predict from the sum of the individual components. The swarming of bacterial cells on surfaces is a fascinating example of what might be considered emergent or multicellular behavior." Such issues are important, notes Weibel, as <a href="http://www.news.wisc.edu/video/bact/052908_SwarmingEdge/">swarming behavior in bacteria</a> can switch on genes that transform benign bacterial cells into pathogens. For instance, the bacterial films that form on catheters and other biomedical devices and expose patients to serious infection arise from a bacterium's tendency to live and migrate collectively. Weibel is also attempting to develop imaging techniques that will help science resolve how the internal scaffolding of cells, the cytoskeleton, is organized in space and time. That, in turn, could lead to new methods to alter the shape of cells. "In bacteria, cell shape is typically conserved. A rod-shaped cell always produces a rod-shaped offspring and a sphere always produces spheres," according to Weibel. "But it's possible to turn a rod-shaped bacterium into a cube or a right-handed coil. Or you can take a rod and engineer a kink in it. We want to understand how shape is connected to the underlying cytoskeleton and how this system controls the spatial and temporal location of other components in the cell." Teasing out those secrets, he says, could help scientists develop novel antibiotics at a time when there is a critical need to replenish the antimicrobial armamentarium in response to germs that have evolved resistance to conventional antibiotics. UW-Madison biochemist Doug Weibel has received a prestigious Searle Scholar Award. Studies of cell traits nets big award for UW-Madison researcher 15344 2008-06-24T00:00:00-05:00

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<a href="http://www.biochem.wisc.edu/faculty/kimble/">Judith Kimble</a>, a University of Wisconsin-Madison professor of biochemistry and genetics and Howard Hughes Medical Institute investigator, has been elected to a three-year term as councilor for the <a href="http://www.nasonline.org/site/PageServer">National Academy of Sciences</a> (NAS). Kimble was one of four new councilors elected to the 17-member NAS governing body. NAS is a private, nonprofit institution that provides science advice under a congressional charter. With about 2,000 members in the United States and 350 foreign associates, NAS is recognized as one of the leading scientific bodies in the world. Members are elected, recognition considered to be one of the highest honors that can be accorded to a scientist or engineer. Judith Kimble, a University of Wisconsin-Madison professor of biochemistry and genetics and Howard Hughes Medical Institute investigator, has been elected to a three-year term as councilor for the National Academy of Sciences (NAS). Biochemist Kimble elected National Academy councilor 14833 2008-02-27T00:00:00-06:00

14306

Experts have been warning for years that foods loaded with high-fructose corn syrup and other processed carbohydrates are making us fatter. Now, a UW-Madison study has uncovered the genetic basis for why this is so. <div id="story_image_325" class="inline-content photo right" style="width: 370px"> <img src="http://www.news.wisc.edu/story_images/0000/0325/mouseTrio_47_s.jpg" alt="Photo of mice from study" /> Research led by biochemistry and nutritional sciences professor James Ntambi shows that mice, at right, lacking a gene called SCD-1 in their livers stay skinny on a high-carbohydrate diet, but grow plump, like the mouse at left, on a high-fat one. The findings suggest that the gene’s action in the liver is what causes weight gain on diets rich in carbohydrates, because deleting the gene protects the mice from getting fat when fed starchy and sugary foods. Photo: courtesy <a href="http://www.biochem.wisc.edu/medialab/">Biochemistry Media Center</a> </div> Writing in the December issue of <a href="http://www.cellmetabolism.org/">Cell Metabolism</a>, a team led by biochemistry and nutritional sciences professor <a href="http://www.biochem.wisc.edu/faculty/ntambi/">James Ntambi</a> reports that a gene in the liver, called SCD-1, is what causes mice to gain weight on a diet laden with carbohydrates. The gene encodes the enzyme SCD, whose job is to synthesize fatty acids that are a major component of fat. When the scientists fed a starch- and sugar-rich diet to mice lacking SCD-1 in the liver, the extra carbohydrates were broken down rather than being converted into fat and stored — keeping the mice skinny. Meanwhile, control mice with normal gene activity grew plump on the same food. "It looks like the SCD gene in the liver is responsible for causing weight gain in response to a high-carbohydrate diet, because when we take away the gene's activity the animals no longer gain the weight," says Ntambi. "These findings are telling us that the liver is a key tissue in mediating weight gain induced by excess carbohydrates." The results could have implications for stemming the skyrocketing obesity problem in people, Ntambi adds. He explains that people pack on pounds in two ways, one of which is to eat extra fat, which then accumulates in adipose, or fat, tissue. But the main cause of weight gain is excess carbohydrates, because they trigger the body to produce new fat. Blocking SCD's action in the liver could therefore offer another means to help people lose weight, Ntambi says, especially since obese people appear to have higher levels of the enzyme than do thin people. "We think that obese individuals, in general, may have higher SCD activity in both the liver and in adipose tissue," he says. "So they may have a higher capability of converting carbohydrate into fat." High-carbohydrate diets have become exceedingly common not only in western nations but also in the developing world, as sugary ingredients such as high-fructose corn syrup have crept into all sorts of processed foods, including soft drinks, baked goods, condiments — even supposedly healthy items such as low-fat, fruit yogurt. What Ntambi's team has now demonstrated is how those diets can act directly on a gene to boost fat synthesis and storage. "This is a very good example of a diet-gene interaction," he says. The current study builds on previous work, in which Ntambi and his colleagues created mice that lacked SCD-1 everywhere in the body, including the liver, muscle, brain, pancreas and adipose tissue. No matter how much they ate, the mice didn't gain weight on either a high-fat or a high-carbohydrate diet. "But it was very difficult to tell which tissue was responsible for the effect," says Ntambi. To tease this out, he and his colleagues subsequently bred mice that lacked SCD-1 in the liver only and placed them on either a high-fat diet or a high-carbohydrate, low-fat one. Much to their surprise, the mice on the high-fat diet gained weight just as quickly as normal, control mice. "This suggests that in weight gain induced by a high-fat diet, other tissues beyond the liver are involved," says Ntambi. In contrast, the mice stayed thin when they feasted on food heavy in starch and table sugar, or sucrose. They were also protected from the condition known as fatty liver. Ntambi thinks what's happening is that in the absence of SCD, the liver has no way to convert surplus carbohydrates into fat, causing the body to break them down instead. The findings also highlight the central role of the enzyme and its main product, a fatty acid known as oleic acid, in overall carbohydrate metabolism, he adds. For example, mice lacking SCD could no longer make glucose — the sugar burned by cells for energy — leading to abnormally low blood sugar levels, or hypoglycemia. They also weren't able to make glycogen, a short-term storage form of glucose. "It looks to us that if you don't have enough oleic acid — which the SCD enzyme makes — then the carbohydrate does not proceed through normal glucose metabolism," says Ntambi. As further evidence of this, when the scientists supplemented the mouse diets with oleic acid, normal metabolism was restored. In both mice and people, on the other hand, eating lots of carbohydrate appears to boost SCD activity, leading to a glut of oleic acid, increased fat storage — and, over time, obesity. "Too much carbohydrate is not good," says Ntambi. "That's basically what we are saying." Ntambi's study was supported by the National Institutes of Health and the American Heart Association. Experts have been warning for years that foods loaded with high-fructose corn syrup and other processed carbohydrates are making us fatter. Now, a University of Wisconsin-Madison study has uncovered the genetic basis for why this is so. Waistline growth on high-carb diets linked to liver gene 14507 2007-12-04T00:00:00-06:00

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Each week, graduate students and postdocs arrived with data and arguments at the ready, prepared to discuss the progress of their research at the round table in <a href="http://www.biochem.wisc.edu/faculty/frey/">Perry Frey</a>'s office. The students presented their findings one by one and waited nervously for their professor's response. "Those weekly meetings could be pretty stressful, especially early on," says Adrian Hegeman, an assistant scientist at the University of Wisconsin-Madison Biotechnology Center and a former student in Frey's biochemistry lab at UW-Madison. "But they really kept everyone on track and allowed Perry to constantly monitor our progress as young scientists." It's a common memory for dozens of graduate students who learned under the tutelage of Frey, UW-Madison's Robert H. Abeles Professor of Biochemistry. A pioneer in the field of radical-mediated enzyme reactions, Frey has been a leader and mentor in the field of biological chemistry for more than two decades. In recognition of his career achievements, the American Chemical Society's Division of Biological Chemistry is hosting a symposium in Frey's honor on Wednesday, Aug. 22, during the society's annual meeting in Boston. Frey has acted as the ACS' associate editor of biochemistry for the past 15 years. He has also served on the executive committee of the Division of Biological Chemistry and held the position of chair from 1990-92. Since beginning his research career at UW-Madison in 1981, he has been elected to the National Academy of Sciences (1998), the American Academy of Sciences (2003) and the American Association for the Advancement of Sciences (2003). In 2000, he received the ACS Division of Biological Chemistry's Repligen Award, an honor that his mentor, Professor Robert H. Abeles of Brandeis University, received years earlier. "My work has gone better than I ever imagined that it would," Frey says. "I've accomplished far more than I could contemplate. And it's not just because of me, it's because of advancements in science. We can do things we couldn't even think about doing 20 years ago." While Frey has received great accolades for his science, colleagues and students see him first as a kind, humble man who is a dedicated mentor. "It is difficult to single out lessons learned from Perry," says former student John Richard, now a professor of chemistry at the State University of New York at Buffalo, "but even harder to think of an area of my conduct that has not been strongly influenced by our interactions. He has been a superb role model." Richard is one of several former students who will speak at the symposium next week. No doubt the opportunity will arise to reminisce about Frey's round table and his notorious lab meetings. Stressful though they may have been, those sessions did the trick. "After a few years of this, you would get pretty good at constructing arguments and designing experiments that would convince Perry that you had addressed every contingency," Hegeman says. "By the last year he would pretty much just smile and ask questions as we presented a near seamless argument." The American Chemical Society's Division of Biological Chemistry will host a symposium in recognition of a UW-Madison biochemist's career achievements. Biochemist Frey honored for career leadership 14001 2007-08-16T00:00:00-05:00

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Two faculty members of the University of Wisconsin-Madison have been elected Fellows of the American Academy of Arts and Sciences. <a href="http://www.cs.wisc.edu/%7Edewitt/">David Dewitt</a> and <a href="http://www.biochem.wisc.edu/record/">M. Thomas Record</a> are among 203 new fellows selected this year in recognition of their "preeminent contributions to their disciplines and to society at large." DeWitt, John P. Morgridge professor of computer sciences, researches database system design and implementation. Record, John D. Ferry professor of chemistry and biochemistry, investigates physical interactions of DNA and proteins in bacteria to understand the control of genetic information. The academy, founded in 1780, is an independent policy research center that focuses on interdisciplinary studies and public policy research. Elected members are drawn from leaders in the sciences, humanities, arts, business, and public affairs. The new fellows will be inducted in a ceremony October 6, in Cambridge, Mass. Two faculty members of the University of Wisconsin-Madison have been elected Fellows of the American Academy of Arts and Sciences. Two faculty named American Academy fellows 13732 2007-04-30T00:00:00-05:00

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Polycystic ovary syndrome (PCOS) is characterized by infertility due to anovulation, abnormal secretion of androgens and other hormones, and insulin resistance. PCOS is the most common female endocrine disorder, affecting 4-7 percent of women in their reproductive years — the syndrome accounts for 75 percent of all anovulations. PCOS has staggering adverse physiological, psychological and financial consequences for women’s reproductive health. <div class="headshotRight"> <img src="http://www.news.wisc.edu/wisweek/11-Apr-2007/images/Assadi-Porter_Far_hs07_7338.jpg" alt="Photo of Assadi-Porter" width="100" height="149" /> Assadi-Porter </div> With funding from the <a href="http://discovery.wisc.edu/">Wisconsin Institutes for Discovery</a> (WID) seed grant program, UW–Madison scientists will now use their collective expertise to develop the first diagnostic test for PCOS. The interdisciplinary nature of the work requires four equal principle investigators leading a team of 12 researchers. Leaders are <a href="http://www.biochem.wisc.edu/faculty/markley/assadi-porter/">Fariba Assadi-Porter</a>, staff scientist of biochemistry; <a href="http://www.nmrfam.wisc.edu/~eghbalni/">Hamid Eghbalnia</a>, assistant scientist of biochemistry and mathematics; Michael Shortreed, associate scientist of chemistry; and Leah Whigham, associate scientist of obstetrics and gynecology. They will steer efforts to develop a novel “metabolic analysis” method to detect and statistically model changes in a subset of molecules within the body’s total pool of metabolites that have proven to be reliable, early indicators of PCOS. The method will derive from measuring biomarkers in women as well as in rhesus monkeys with PCOS at the <a href="http://www.primate.wisc.edu/">Wisconsin National Primate Research Center</a>. These animals have been well characterized and studied during the past two decades by David Abbott, professor of obstetrics and gynecology. “The idea is to use a nonhuman primate model of PCOS in parallel with human samples to develop a novel diagnostic test,” says Assadi-Porter. “With this, we will begin to analyze patient samples to develop the portrait of PCOS in humans. Our approach could be used to develop similar tests for a variety of other diseases.” The strength of the team’s grant application was its description of a highly innovative and challenging approach that uses a combination of technologies and resources unique to UW–Madison. The researchers plan to use stable isotopes, NMR, MS and advanced mathematical computation, which are all centered around clinical and medical sciences with broad clinical applications. The investigators also established their project’s relevance to the WID mission of advancing knowledge, inventions, treatments, cures and economic development through their previous patents with the Wisconsin Alumni Research Foundation for several inventions related to this proposal. The other team members are animal sciences professor Mark Cook, obstetrics and gynecology professor Steven Lindheim, biochemistry professor John Markley, zoology professor Warren Porter, chemistry professor Lloyd Smith, and researchers Daniel Butz and Marco Tonelli. Polycystic ovary syndrome (PCOS) is characterized by infertility due to anovulation, abnormal secretion of androgens and other hormones, and insulin resistance. PCOS is the most common female endocrine disorder, affecting 4-7 percent of women in their reproductive years — the syndrome accounts for 75 percent of all anovulations. PCOS has staggering adverse physiological, psychological and financial consequences for women’s reproductive health. http://www.wid.wisc.edu/research/seedgrants/pcos.html Researchers seek early detection for hard-to-diagnose disease 13653 2007-04-10T00:00:00-05:00

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By subtracting a single gene from the genome of a mouse, scientists have created an animal that can eat a rich, high-fat diet without adding weight or risking the complications of diabetes, according to a new study published this week. Writing in the online editions of the Proceedings of the National Academy of Sciences (PNAS), James M. Ntambi, a professor of <a href="http://www.biochem.wisc.edu/">biochemistry</a> and of <a href="http://www.nutrisci.wisc.edu/">nutritional sciences</a> and colleagues report that mice lacking a gene known as SCD-1 can eat a rich high-fat diet and avoid the consequences of fat deposition and excess sugar in the blood, the hallmark of type II diabetes. The new finding, says Ntambi, provides insight into the central genetic mechanisms that underpin diet and metabolism, and suggests it may one day be possible to devise drugs to effectively protect against obesity and diabetes. The gene SCD-1 produces an enzyme known as SCD that is required for the body to make the major fatty acids that reside in fat tissue. Ntambi, who collaborated in the study with Alan Attie a professor of biochemistry at UW-Madison and Jeffrey M. Friedman, a Howard Hughes Medical Institute investigator at Rockefeller University, says the mice lacking the SCD-1 gene defied every attempt to make them fat. "The idea was to make them fat," Ntambi says, "but the mice lacking the SCD-1 gene never got up there despite a diet that contained nearly 15 percent fat. What we found is that when you feed these animals a high-fat diet for several weeks, they fail to accumulate fat over time." The effect, according to the PNAS report, seems to be systemic. In the mice lacking the SCD-1 gene, fat does not accumulate in the liver or other tissues where, under normal circumstances, it would gather and contribute to health problems typically associated with diet and obesity, says Ntambi. Instead, the excess fat seems to be metabolized: "We have biochemical evidence that the mice burn the excess fat," says Ntambi. "The protection from obesity involves increased energy expenditure and increased oxygen consumption." Attie says that while the surface effects of removing the SCD-1 gene are not entirely unique, it is notable that the model provides a glimpse of the metabolic mechanisms that underpin those effects: "The fact that you're increasing metabolic rate as a result (of knocking out the gene and its enzyme products) is really interesting." He notes that while the mice are more insulin sensitive, further tests will be needed to see if they are indeed protected from diabetes. But the absence of the SCD-1 gene does keep glucose levels in the blood low. Diabetes is characterized by a deficiency of insulin and high levels of sugar in the blood. "These animals are more insulin sensitive and don't become diabetic," Ntambi says. "After eating, glucose levels rise, but within a very short time the glucose goes down and stays down." Control animals with the SCD-1 gene, fed the same rich diet, have higher blood glucose levels for longer periods of time. "All of this goes hand in hand," says Ntambi. "Most people who are diabetic have the condition due to the amount of fat. That's what causes insulin resistance and keeps glucose levels in the bloodstream high." Drugs to prevent obesity would be of significant importance in terms of public health as the U.S. Centers for Disease Control and Prevention estimates that 20 percent of Americans suffer from obesity. Diabetes, as well, is a significant health problem in the U.S. and elsewhere with an estimated 17 million Americans suffering from the disease. The mouse SCD-1 gene was found and cloned by Ntambi and colleagues in 1988 when he was a post-doctoral fellow with Daniel M. Lane at the Johns Hopkins University Medical School in Baltimore. He developed the knockout mouse model in 2000 while on the Wisconsin faculty. The human equivalent of SCD-1 was recently found and Ntambi's group is studying that gene's function in tissue culture. In mice, the elimination of the SCD-1 gene does have side effects, Ntambi and co-author Makoto Miyazaki a biochemist at UW-Madison acknowledged, notably skin and eye problems as the animals age. However, in separate studies Ntambi and Miyazaki have shown that mutant mice with half the level of the enzyme appear normal. In these mice, the side effects observed in mice lacking the SCD-1 gene are absent. This suggests, says Ntambi, that it may be possible to develop drugs to suppress the fatty acids produced by SCD-1 and confer protection against obesity and perhaps diabetes while minimizing or eliminating side effects. In addition to Ntambi, Attie, Friedman and Miyazaki, co-authors of the PNAS paper include Jonathan P. Stoehr, Hong Lan, Christina M. Kendziorski, Brian S. Yandell and Yang Song, all of UW-Madison. Paul Cohen is a co-author from the Joint Tri-institutional M.D.-Ph.D. Program of Rockefeller University, Weill Medical College of Cornell University and Sloan-Kettering Institute. Scientists have created an animal that can eat a rich, high-fat diet without adding weight or risking the complications of diabetes Subtract a gene and feasting mice add no fat 7709 2002-09-12T00:00:00-05:00 2002-08-13T00:00:00-05:00

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