University of California, San Diego: External Relations: Research

Scientists Successfully Grow Insulin-Secreting Cells to Treat Diabetes
Scientists Successfully Grow Insulin-Secreting Cells to Treat Diabetes

UCSD School of Medicine scientists have successfully cultured human beta cells that grow indefinitely, and that could potentially serve as an unlimited source of insulin-producing tissue for transplantation to cure people with diabetes, according to reports presented at the American Diabetes Association's 60th Annual Scientific Sessions in San Antonio. Beta cells are found exclusively in the pancreas, secreting insulin in response to glucose stimulation. When these cells are defective or when the body fails to utilize insulin properly, the result is diabetes, characterized by high blood sugar levels. More than 16 million Americans have diabetes, the sixth leading cause of death by disease in the United States. One approach to treating diabetes is transplantation of either the pancreas or of islet cells which contain beta cells, giving the patient a new source of insulin. Recent advances in these techniques indicate that this is a successful approach, but limited due to the scarcity of donor tissue from cadavers. "Even if you had unlimited success with tissue transplantation, there is simply not enough donor tissue to treat the millions of people who have diabetes," said Fred Levine, M.D., Ph.D., associate professor at the UCSD Cancer Center and the Whittier Institute in San Diego, whose laboratory reported the successful results. "We have now been able to create an immortal human cell line, and have demonstrated in mice that these cells are functional when transplanted, secreting insulin in response to glucose stimulation."

Improving Safety Through State-of-the-Art Technologies
Improving Safety

The Structural Engineering Department is using cutting-edge technology to improve the safety of the nation's buildings, bridges, and highways. The department is collaborating in the Caltech-CUREe Woodframe Project, an initiative to reduce damage to residential buildings during earthquakes. UC San Diego is leading the testing component of the project and in 2000 completed the first fully dynamic earthquake test ever performed on a full-scale building in the U.S. These tests, simulating ground motions of recorded earthquakes, will lead to improved building design codes. For more information on the CUREe project, visit the CUREe web site.

Structural Engineering faculty are also applying state-of-the-art technology to the construction of a new highway bridge on State Route 86 near the Salton Sea. The Kings Stormwater Channel Bridge is unique in that it will be primarily composed of glass and carbon composites. It will be the only all composite bridge in California and the only one in the world to carry heavy traffic. Caltrans and DARPA (Defense Advanced Research Projects Agency) are partnering with the UC San Diego on the project.

Two-Drug Combination Therapy Shows Promise Against Melanoma
Melanoma researchers at University of California, San Diego (UCSD) have developed a new drug-combination therapy that has proven in Phase II clinical trials to be significantly better at extending patients' lives than any other drug therapy. The two drugs, tamoxifen and cisplatin, are commonly used chemotherapeutic agents. Interestingly, neither drug, when used alone, has proven effective against melanoma. "For reasons that aren't yet clear, this combination creates a synergism that is highly toxic to melanoma cells," said Edward F. McClay, M.D., principal investigator of the study and director of the Melanoma Care Unit at UCSD Cancer Center. Results of the clinical trial are being published in the July 2000 issue of the British Journal of Cancer. The clinical trial was based upon earlier laboratory work in which McClay and colleagues first identified this synergistic interaction.

Analyzing the Role of Aerosols in Global Warming

Scientists participating in the international Indian Ocean Experiment have determined that dense pollution produced in Asia and the Indian subcontinent is significantly disrupting the natural atmosphere over the Indian Ocean and raises serious environmental questions. The new evidence also suggests that rather than being an isolated concern, the extensive pollution may have global implications. The $25 million project with more than 150 international scientists has shown that a dark haze layer of tiny particles called aerosols is reducing the sunlight reaching the surface of the Indian Ocean by several percentages. The project is coordinated by the Center for Clouds, Chemistry and Climate (C4) at Scripps Institution of Oceanography. Regional consequences of global warming depend critically on the potentially large effect of aerosols, particles about a millionth of a centimeter or smaller in diameter. These aerosols, consisting of sulfates, soot, organic carbon, and mineral dust, are produced both naturally and by human activities.

Understanding the Genetics of Introduced Pests

Researchers in UCSD's Division of Biological Sciences have discovered that the proliferation in California of the introduced Argentine ant, a major pest that has invaded homes and displaced native ants in coastal regions of the state, is due to the lack of genetic diversity among individuals. Their findings, described in the Proceedings of the National Academy of Sciences, suggest that this reduced genetic variation has contributed to the growth of a giant "supercolony" of ants stretching nearly the length of the state. The reason is that these genetically similar ants cooperate rather than fight for resources as their genetically dissimilar cousins do in their native country. Until now, conservation biologists believed that genetic similarity within populations was unhealthy. But this discovery overturns that assumption and suggests that the success of many other introduced, territorial pests�such as the fire ant�may be due to their genetic similarities.

UCSD Team Demonstrates Potential For Widely Effective Cancer Vaccine
Vaccination against an enzyme common to a variety of human tumors might effectively mobilize the body's own immune system to attack and kill cancer cells, scientists from the UCSD School of Medicine and Cancer Center report in the April 4 issue of the Proceedings of the National Academy of Science (PNAS). Telomerase, an enzyme involved in maintaining normal chromosome length during cell replication and key to the uncontrolled replication of cancerous cells, is considered the first gene to play a direct role in tumor transformation of cells by allowing precancerous cells to become immortal. A team led by Maurizio Zanetti, M.D., UCSD professor of medicine and member of the UCSD Cancer Center, in collaboration with the Institut Pasteur in Paris, has now successfully used a prototype vaccine in cancer cells in vitro to activate a type of lymphocyte called cytotoxic T-lymphocytes (CTL), or killer cells, to destroy cancer cells using telomerase as a target. Lymphocytes are white blood cells that patrol the body and, when they encounter foreign cells, launch an attack against the invader. Killer cells target infected or cancerous cells by recognizing and binding to proteins, or antigens, on the cell surface. �In cancer, the immune system becomes increasingly weakened and ineffective against rapidly proliferating malignant cells," said Zanetti. �We wanted to see if the immune systems of individuals with cancer retained the ability to recognize telomerase, and if we could boost the immune response using telomerase in a prototype vaccine to expand CTL activity against cancer."

'CAT-Scans' of the Solar Wind
S.E.M.I.

Energetic solar eruptions known as "coronal mass ejections" can produce geomagnetic storms on Earth that interrupt satellite communications, damage spacecraft, produce destructive surges in power grids and even increase radiation exposure to people flying in airplanes. While space-weather forecasters issue warnings whenever they detect a solar eruption, most of these mass ejections of energetic electrons bypass Earth. These forecasts have been dramatically improved by a method developed by UCSD physicists of pin-pointing these electron clouds as they travel through space�producing a kind of three-dimensional CAT scan of the solar wind.

Faster Earthquake Mapping Created
Using satellite technology and radar images, scientists at Scripps Institution of Oceanography produced near real-time images of a magnitude 7.1 earthquake. Scientists use maps of ground displacement, called surface deformation, to locate stress points and other structures in the underlying faults. Geologists take these maps into the field and look for evidence of ground motion along the faults. While such maps typically take weeks or months to compile following a quake, the Scripps data were collected directly from a satellite as it passed over southern California about three days after the October 16, 1999 Hector Mine earthquake near Twenty-Nine Palms, California. The researchers used a satellite system and a bank of computers on the Scripps campus to capture the images of ground displacement in a 100 x 100 kilometers grid centered at the earthquake's epicenter. "Some of these changes are so subtle they cannot be seen by aircraft. It is very important to do the field mapping soon because the tiny surface fractures will degrade after just one rain storm," said David Sandwell, professor of marine geophysics at Scripps's Cecil H. and Ida M. Green Institute of Geophysics and Planetary Physics (IGPP). "With a little practice, the turnaround time could come down to about four hours, even closer to real-time capability."

Preventing 'Pod Shatter'
Pea Pod

Each year, farmers of canola seeds, a $9-billion-a-year industry, lose as much of half of their crop through pod-shatter, a mechanism the plant uses to disperse its seeds. A team of UCSD biologists has discovered the genes responsible for this process, allowing farmers to prevent it and double their yields of this valuable crop.

A Shocking Discovery
Jacobs School Bioengineers prevented shock and multiple organ failure in experimental animals by blocking powerful pancreatic digestive enzymes in the intestine. This fundamental breakthrough could lead to therapies to prevent and treat ischemic shock in people who experience shock following blood loss from traumatic injury or high-risk surgery each year. The work also provides clues into the cellular mechanisms that lead to shock. The research report titled "Generation of In Vivo Activating Factors in the Ischemic Intestine by Pancreatic Enzymes" was published in the Proceedings of the National Academy of Sciences on February 15, 2000. The work was funded by the National Heart, Lung, and Blood Institute, and the principal investigator of the study was Geert Schmid-Schoenbein, professor of bioengineering at the Jacobs School.

Robotic freeways - Clean-up in Lane 5
Electrical and Computer Engineering faculty at the Jacobs School are working in collaboration with UC Santa Barbara to improve safety and reduce congestion on highways through a detection system that networks novel sensors to mobile robotic agents. The $4 million project is funded by the California Digital Media Innovation Initiative and Caltrans. For more information on this project, go to http://swiftlet.ucsd.edu/. Also, the project was recently mentioned in Popular Mechanics (May 2000). A copy of the article can be found at [IMG].

Coastal Data Aids Search Efforts
Buoy

Scientists at Scripps Institution of Oceanography provided data that aided search efforts following the January 2000 crash of Alaska Airlines Flight 261 off the southern California coast. Researchers with Scripps's Coastal Data Information Program (CDIP) developed a web site, exclusively for rescue workers, that displayed predictions of wave height and period at the crash site several days in advance. The information provided was critical for coordinating the search. Users included the Oxnard branch of the National Weather Service, which used the data to brief the U.S. Navy search ship twice a day, and the U.S. Coast Guard.

New Vaccine Technology Achieves Dramatic Immune Response in Mice
UCSD School of Medicine scientists reported in the May issue of Nature Biotechnology a potentially powerful new approach to vaccine protection against cancer, infectious disease and allergy, based on immune response-boosting DNA technology derived from microorganisms linked to tuberculosis. A century ago, physicians noted that patients whose TB had invaded their bladders seemed to develop a protection against bladder cancer. This observation led to clinical treatment using cell extracts from mycobacterium Bacille Calmette-Guerin (BCG), a strain of TB-like bacteria that does not cause disease. Patients with bladder cancer treated with BCG extract experienced lower rates of cancer recurrence. In 1984, a Japanese group isolated the "active ingredient" responsible for the anti-tumor effect of BCG extract--a specific class of previously unknown DNA sequences that restrict tumor growth. Subsequent studies have shown that these immunostimulatory DNA sequences (ISS) act by stimulating immune response. The UCSD team has now demonstrated in mice that a new class of vaccines consisting of ISS chemically conjugated to protein (protein-ISS conjugate or PIC) can be used as a powerful immune enhancing agent, directly targeting the cellular switch that turns on the body's defensive reaction against foreign invaders. The successful use of this new vaccine technology not only clarifies how ISS works at the molecular level, it also opens doors for a new approach to clinical therapy for cancer, infection and allergic reaction.

Scientists Develop Transgenic Mouse that Models Parkinson's and Related Disorders
The first mouse model genetically programmed to simulate motor deficits and brain alterations found in Parkinson's disease and related disorders has been developed by a team of scientists at the University of California, San Diego; the University of California, San Francisco, and the Gladstone Institute of Neurological Disease. The research was led by Eliezer Masliah, M.D., of the UCSD Departments of Neurosciences and Pathology. The investigators report in the Feb. 18 issue of Science that mice bred to express a human protein called alpha-synuclein in the brain develop protein deposits in specific brain regions associated with Parkinson's disease, and also have impaired motor function. "Previous studies have shown increased levels of this protein in the brain cells of Parkinson's patients, but whether they were a cause or result of the disease has not been clear," said Masliah. "With these results we have demonstrated that alpha-synuclein is in fact involved in the onset of diseases such as Parkinson's. The development of symptoms in these genetically altered mice resembles disease progression in humans. This gives us a new model for studying Parkinson's disease and related disorders such as Alzheimer's disease."

Flower-Within-a-Flower
Wild Flower

What makes a flower produce a flower within a flower? UCSD biologists solved this 2,000-year-old puzzle about one of the earliest-recognized botanical abnormalities�flowers that turn their reproductive organs into more flowers, leading to flowers within flowers within flowers. Their discovery of trio of identical genes, all of which must be turned off for this trait to appear, is prompting plant geneticists to rewrite the textbooks on flower development.

No Strings Attached
IEEE Personal Communications (October 1999, vol. 6 No. 5) devoted the entire publication to describing current UC San Diego research at its Center for Wireless Communications (CWC). As companies bring the first Web-linked mobile phones and personal communicators to market, CWC is working on the next generation of technology that will allow society to reap the full benefits of mobile Internet access. The CWC, part of the university's Jacobs School of Engineering, is a shining example of the role research universities can play in driving economic progress Its industry partners range from Hewlett Packard and Qualcomm to Fuji Electric, Nokia, and Kyocera. For more information on the CWC web site.

New Three-Dimensional Laser Imaging Instrument Developed

A newly developed laser instrument designed by researchers at Scripps Institution of Oceanography will allow scientists and other ocean explorers to peer through the dark depths of the ocean like never before. Using a sophisticated scanning device and laser technology, the "3-D Sea Scan" instrument produces vivid three-dimensional "movies" of life on the sea floor. This level of detail gives scientists a new tool for understanding marine ecology and depicting biological activity, according to Jules Jaffe, the project director. 3-D Sea Scan is an optical imaging system that can view objects and organisms with a range of accuracy down to a thickness of a penny and lateral resolution to 1/25th of an inch. The U.S. Navy has sponsored the development of 3-D Sea Scan to help detect underwater mines. Other commercial uses for 3-D Sea Scan include three-dimensional sensing of underwater pipes used in oil and gas lines. 3-D Sea Scan also can give marine archeologists a way of three-dimensionally characterizing sunken ships, wreckage, and other objects. "The future of imaging is going to be three-dimensional," said Jaffe. "This instrument will be the precursor of a whole new generation of imaging systems." Visit the Jaffe Laboratory for Underwater Imaging.

Faults Discovered Underneath Metropolitan Los Angeles
Scripps Institution of Oceanography Professor Peter Shearer and his colleagues conducted extensive seismological research that led to the discovery of blind thrust faults underneath downtown Los Angeles. These faults, capable of producing a devastating earthquake, pose a more serious threat to Los Angeles than the more famous and much larger San Andreas Fault. Although scientists have long thought the faults existed, the research provides the first solid proof.

Pinpointing a New Source of Methyl Bromide
Research scientists at Scripps Institution of Oceanography have identified salt marshes as a major natural source of the environmentally and economically important compound methyl bromide. Although they make up only 0.1 percent of the earth's surface, salt marshes may be responsible for producing approximately a surprising 10 percent of the total methyl bromide and methyl chloride budget, the researchers found. Methyl bromide is produced naturally from oceans and plants on land. But it is also widely manufactured around the world because of its effectiveness as a pesticide against insects, nematodes, weeds, pathogens, and rodents. Methyl bromide also is generated as a by-product of leaded fuel combustion and vegetation burning. The U.S. Environmental Protection Agency (EPA) estimates that 72,000 tons of methyl bromide is used around the world each year. Scientists estimate that about half escapes into the atmosphere. Experts say that 20 percent of the methyl bromide that reaches the atmosphere can be attributed to fumigation, about 10 percent to vegetation burning, and roughly 30 percent to production from the oceans. But the balance of this methyl bromide budget, a significant 40 percent, was missing. The new research uncovers about 10 percent of the absent budget.

Low Carbon Dioxide Levels May be Caused by Sea Ice
Researchers at the University of Colorado and Scripps Institution of Oceanography have reported that variations in Antarctic sea ice may have played a significant role in lowering atmospheric carbon dioxide (CO2) concentrations during the last ice age. The finding makes progress toward unraveling the mysteries of the past climate changes, a necessary step for predicting future climate. According to ice core records, every hundred thousand years or so, the earth cycles between warm periods and cold glacial periods, with Antarctic temperatures varying by about 20 degrees Fahrenheit. Records also indicate that during the glacial periods there was 30 percent less CO2 in the atmosphere. The finding attempts to solve the mystery of the connection between global atmospheric CO2 concentrations and Antarctic temperatures, which seem to rise and fall together. Carbon dioxide is one of the most important greenhouse gases. While it is a naturally occurring gas, it also has been increasing in the atmosphere. Many believe this increase is due to human activities and raises concern about global warming.

Storing Uncle Sam's E-mail
The San Diego Supercomputer Center's (SDSC) Data-Intensive Computing group and UCSD colleagues recently solved a major problem facing the National Archives and Records Administration: how to save millions of U.S. government e-mail messages and store them indefinitely.

Designing the Future of the Internet
SDSC researchers in the Cooperative Association for Internet Data Analysis (CAIDA) are helping to design the future of the Internet. In just one activity, CAIDA and its industry partners are establishing training laboratories at 25 universities across the country to educate the next generation of Internet architects.