NC State University News Services CB 7504 Raleigh, NC 27695 (919) 515-3470 [email protected] http://www.ncsu.edu/news

Jan. 27, 1999

A roundup of NC State University research activities. For use by the media as briefs or as background for stories. For more information or copies of press releases on these research activities, or for help contacting the researchers, contact Tim Lucas, NC State News Services, at (919) 515-3470 or [email protected], Texts of press releases are accessible electronically via News Services' Web site at www.ncsu.edu/news.

Medicine From the Swamp

An NC State University scientist has developed the world's first process to genetically engineer duckweed, a common aquatic weed, into a bioproduction system capable of making insulin and other therapeutic proteins and industrial enzymes.

The beauty of the process, says creator Dr. Anne-Marie Stomp, lies in duckweed's rapid growth, high protein content, self-cloning ability and unique growth habit. "This weed is going to be the premier protein production system of the future," she says. "It's potentially less expensive and more productive than systems using mammalian cells, tobacco or soybeans. And it's more flexible. It can grow in a stainless steel vessel, a greenhouse or a wastewater lagoon." That means it can be grown in the ultraclean conditions required for drug proteins, as well as the low-cost, large-scale production needed for industrial enzymes.

Stomp has applied for a patent and launched a company, Biolex Inc., to market the process, and already has the backing of three major investment funds. The market for therapeutic proteins is worth about $10 billion annually, she notes, and in a few years, as patents expire on the oldest protein drugs, "drug makers will be searching for new and cheaper production systems, like mine."

Reclaiming a Piece of Christianity's Past

The search for a lost Roman city buried beneath the modern Red Sea resort town of Aqaba, Jordan, has led an NC State University archeologist to an unexpected find -- a structure that may be the world's oldest Christian church. Last summer, after four seasons of digging, Dr. Thomas Parker and his team discovered the ruins of a church and cemetery surrounded by coins, lamps, glassware, pottery and other artifacts. "All lines of evidence are converging to support the date of the church and its place in history," Parker says.

Chief among the articles of proof is part of a brass cross found in the adjacent cemetery, and a coin -- found in what may have been an ancient collection box -- consistent in form and weight with those issued between 290 and 300 A.D. The design of the structure also suggests it was built in that time, Parker says. Like most early churches, it is oriented to the east; was lighted with glass lamps filled with olive oil; and is laid out in a basilica plan, with a nave, apse, chancel and aisles. More study is needed before a date can be established with certainty, Parker says, so he will return in 2000 to search for a wall inscription or other artifacts that will firmly place it in the late 3rd century.

Tiny Sensors May Have Big Impact

NC State University engineers are developing tiny heart sensors, only one-fifth as thick as a human hair, that may help medical researchers reduce the time it takes to study new treatments for heart defects and diseases.

The sensors, designed for use on laboratory mice, are the brainchild of Dr. Troy Nagle, who holds dual degrees in medicine and engineering. Nagle previously developed heart sensors for larger lab animals such as pigs and dogs. "The benefit to creating sensors for mouse hearts is that through genetic engineering we can now create mice with the specific genetic makeup needed to serve as models in medical studies," he says. "This is not yet possible with dogs and pigs."

The sensors measure 20 microns across and have a consistency similar to plastic wrap. Once final design modifications are made, they will be sent to the University of North Carolina at Chapel Hill where cardiac researchers will use them to study how the electrical impulses of the heartbeat spread through the heart and how this electrical activity is changed by medications or disease.

Sinister Signatures in the Sky

Advance warning can spell the difference between life and death for persons living in a tornado's path. But forecasters in the Southeast work at a disadvantage. Their forecast tools and training are based on research in the Midwest, where the super-cell storms that spawn most twisters are different than tornadic storms here.

NC State University meteorologists, led by Dr. Steven Koch, are working with the National Weather Service to identify the differences and devise tools and training programs that will help Southeastern forecasters spot tornadic storms sooner. One of their most significant findings so far is that super-cell mesocyclones that spawn tornadoes in the Southeast are 40 percent to 50 percent more shallow than in the Great Plains. That's important, because due to the earth's curvature, radar images from 100 miles away show what's happening up around 10,000 feet. At that altitude, a shallow mesocyclone could slip by unnoticed until it moved considerably closer or was reported by spotters on the ground, reducing the amount of advance warning that could be given.

A Better Measure of Heart Disease Risk

An NC State University biochemist has developed a new blood test that allows doctors to assess a person's risk of heart disease more accurately than before. The test, created by Dr. James Otvos, uses proton nuclear magnetic resonance spectroscopy to detect 15 subclasses of cholesterol-containing lipoproteins found in blood. Lipoproteins are particles that package cholesterol, allowing it to be transported in the blood. "Before this, we could measure the quantity of 'good' and 'bad' cholesterol in a person's blood, but not the quality -- the different sizes and types of it. Now we can," says Otvos. That's critical, he says, because "it's not cholesterol, per se, that's important in predicting disease; rather it's the size and type of lipoproteins that matter."

Using Otvos' technology, medical researchers already have discovered that certain types of low-density lipoproteins -- the so-called "bad" cholesterol -- aren't as dangerous as others; and that not all types of high-density lipoproteins -- also known as "good" cholesterol -- are protective.

A study documenting the utility and accuracy of Otvos' test has been published in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology.

Concrete Images

When NC State University civil engineer Dr. Neven Krstulovic-Opara talks to people about concrete, he flashes images of the famous Kobe, Japan, earthquake on the projection screen -- gloomy slides of cars crushed beneath cement rubble. "My goal is to make these images things of the past," he says. To do that, he's developed a new process for reinforcing concrete with recycled steel fiber mats. The process adds strength and durability to the concrete and allows it to bend. As a result, the new material resists breaking apart in earthquakes. "Before, during an earthquake, large chunks of concrete could break off buildings and bridges, possibly injuring someone" or crushing structures and vehicles below, Krstulovic-Opara says. With the new material, if the pieces crumble, they will be small enough not to cause injury or serious damage.

New Insights on Down Syndrome

Parents have long suspected that children with Down syndrome are more likely than others to suffer from impaired nutrition. Now, a two-year study led by NC State University scientists suggests those suspicions may be right. In vitro tests of intestinal tissue from normal mice and those with a Down syndrome-model condition showed that mice with the model condition used up to 20 percent more metabolic energy to absorb nutrients from food than did the control mice. "The 'Down syndrome' mice also had a clear derangement in how they metabolized protein," says Dr. Jim Croom. He and his associates at NC State and the Medical University of South Carolina are now conducting in vivo tests to confirm their in vitro findings.

Down syndrome in humans is caused by an extra copy of the 21st chromosome; in mice, the model condition is caused by an extra copy of the 16th. Croom's study, published in the journal Growth, Development and Aging, is the first to show that the impaired metabolisms of the mice correlate to metabolic defects reported in humans with Down syndrome, establishing the mice as the first known viable nonhuman model organisms for studies of the syndrome's effect on human metabolism and nutrition.

In the Beginning, There Was RNA

A study by NC State University scientists has shown, for the first time, that RNA can control gene expression. The study, published in Science, finds that the interaction of two RNA components is responsible for making protein in the red clover necrotic mosaic virus. Though the virus itself isn't an important disease, the discovery may have profound implications in evolutionary biology, says Dr. Steven Lommel, who co-authored the study with colleague Dr. Tim Sit.

"Previously, we knew that RNA had a number of functions, but gene expression was not one of them," Lommel says. "This is the first time we've been able to show that an RNA-to-RNA interaction can turn on a gene. That finding is one more piece of evidence to support the hypothesis that RNA, not DNA, was the first molecule of life."

Relief for Allergic Dogs

Pollen, mold spores and other allergens leave some dogs suffering as much as their owners do. Veterinarians usually treat the irritating skin rashes that result from these allergies with cortisone-like steroids which relieve the itching, but may cause muscle weakness and increased appetite, water consumption and urination.

NC State researchers are searching for better alternatives. Among the potential treatments being evaluated, Dr. Thierry Olivry and his colleagues are using immunotherapy -- repeated, increased-dose injections of allergens -- to reduce dogs' allergen sensitivity. They also are testing the effectiveness of misoprostol and cyclosporine, two drugs used normally for other purposes, for treating late-stage dermatitis, against which cortisone-like steroids aren't very effective. Early results from clinical trials are promising, Thierry says, although more study is needed.

Remember the Alamo...Differently

When NC State University historian Dr. James Crisp agreed to review an amateur historian's book about a Mexican soldier's diary of Santa Anna's attack on the Alamo, he didn't intend to write a new ending to the legend of Davy Crockett. But Crisp's careful study and verification of the 1836 diary of Jose Enrique de la Pena have done just that.

The de la Pena memoir contends that Crockett surrendered at the Alamo and was executed by Mexican soldiers, instead of fighting to the bitter end alongside his fellow Texans. Dismissed by Crockett admirers as a fake, the diary received no respect until historical detective work by Crisp revealed it could be the real McCoy. In 1997, three years after first reading it, Crisp wrote an introduction to a new edition of the diary, published by Texas A&M University Press, in which he presented strong evidence to support its authenticity. Forensics tests of the diary's paper have since confirmed Crisp's conclusion. Last fall, the once "worthless" diary sold to anonymous bidders for $350,000.

A Test for Pests

Crops engineered with the organic pesticide Bacillus thuringiensis, hold great promise for farming because Bt toxin is ecologically more sound than chemical pesticides. Yet scientists worry that bugs may build up resistance to it too quickly. NC State University scientists have created an inexpensive, easy-to-use diagnostic test that gives farmers early warning if resistance to the toxin builds up. The kit, which also can detect a buildup of resistance to chemical pesticides, is about the size and weight of a cellular phone. Farmers put water, pesticide and bugs collected in their fields into the kit, and the next morning, if the bugs' feces are blue, it's a sign of a resistance buildup. In contrast, farmers have to wait days for results from the mortality bioassays now used to test for resistance.

In a paper published in the journal Crop Protection, entomologist Dr. Mike Roe and his colleagues documented their kit's effectiveness for early detection of pests in lab tests. The kits now are being field-tested on cotton crops in six states.

Saving the World's Threatened Trees

NC State University forester Dr. Bill Dvorak has spent 17 years exploring the mountainous terrain and tropical jungles of Latin America in search of endangered trees. As the leader of the university's Central America and Mexico Coniferous Resources Cooperative (CAMCORE), Dvorak has sought out some of the tropics' most threatened species and moved them to safer ground.

About 85 percent of the 8,500 trees and 32 different species replanted by CAMCORE have survived in their new locations, while more than two-thirds of the trees left behind have been lost. In addition to replanting endangered trees, Dvorak and his colleagues from CAMCORE's 33 international member organizations also send some of the rescued trees to plantations where breeders can build up their population; identify species with commercial potential; and breed new lines from the healthiest and most productive specimens. CAMCORE projects now are underway in Southeast Asia, Australia and Africa, as well as Latin America.

Drugs Made From Eggs? It's No Yolk

Most people use eggs to make omelets. NC State University scientist Dr. James Petitte wants to use them to make drugs. Petitte is developing biotechnology that uses early avian embryo cells to produce transgenic chickens, from which drug proteins can be extracted. "Chickens produce proteins very efficiently and cost-effectively," he says. In his process, protein-regulating genes are inserted into embryonic chicken cells that have been cultured using a maturation-retarding technology. The cells then are placed into another embryo. Later, after the embryo matures into a chicken, proteins can be extracted from its eggs or blood.

Because most drugs are protein-based, demand for proteins typically exceeds supply, keeping costs high. By giving drug makers a new source for proteins, Petitte hopes his technology will help keep those costs in check. NC State has been issued three patents on the technology.

Building a Better Juice Box

Juice boxes, the staple of snacks and school lunches everywhere, could become safer for consumers and less expensive to produce with the help of two NC State University engineers. Manufacturers currently sterilize the popular containers in a hot peroxide bath that reduces bacteria on the surface but also leaves an undesirable oxidant residue. However, a new sterilization process developed by Drs. Roger Rohrbach and Mohamed Bourham replaces the peroxide with low-energy electron beams that can deactivate, or sterilize, the bacteria rapidly and at a low cost but without leaving any residue. Rohrbach and Bourham are now working to adapt the electron-beam device for use with brickpack processing machines now used by industry to seal juice boxes.

-- lucas --