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Graduate School of Biomedical Sciences
Gizmos and Gadgets
Making the Invisible...Visible
by Will Sansom
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The amazing core research facilities of the Graduate School of Biomedical Sciences are enough to make anyone exclaim, "These aren’t your grandfather’s microscopes anymore!" In fact, a host of recently acquired multimillion-dollar devices enable the deciphering of disease to the individual cell and molecule.
Some of the new gadgets are in the Core Optical Imaging Facility in the department of cellular and structural biology. This facility is valued at several million dollars and is used by more than 60 Health Science Center laboratories, said Victoria C. Frohlich, Ph.D., research assistant professor. "Optical imaging is a mainstay in science these days," she said. "A technique called fluorescence enables us to observe and measure changes in the environments of single molecules, cells, genes, whole tissues and even organs." The optical imaging instruments are being used in studies of cancer, aging, genetics and neuroscience.
Craig A. Witz, M.D., associate professor of obstetrics and gynecology, uses the instrumentation to look at cell invasiveness in endometriosis and the spread of cancer. "We are studying attachment of endometrial cells (the tissue that lines the cavity of the uterus) to the cells that line the abdominal cavity," he said. "Certain cancers, such as ovarian, endometrial, pancreatic and gastric cancers, spread by invading into different surfaces in the abdominal cavity. Endometriosis has the same sort of characteristics except it is locally invasive. That is why we are looking at the initial steps of attachment."
Shou-Jiang Gao, Ph.D., associate professor of pediatrics, microbiology and medicine, uses a confocal microscope to study cellular invasion by Kaposi’s sarcoma-associated herpesvirus, an opportunistic virus that attacks individuals with weak immune systems. "Our goal is to lock the keyhole to the cell, preventing cancer development caused by the virus," he said.
In May, the Graduate School’s Center for Biomolecular Structure Analysis acquired a state-of-the-art X-ray generator valued at $1.6 million and three nuclear magnetic resonance (NMR) spectrometers valued at $2.6 million. The center is the first in Texas to acquire some of these instruments. Funding is through The University of Texas Permanent University Fund, the Houston Endowment, the National Institutes of Health and the Children’s Cancer Research Center at the Health Science Center. NMR and X-ray crystallography are the two technologies that scientists use to determine the structure of molecules at the atomic level.
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Andrew P. Hinck, Ph.D., and P. John Hart, Ph.D., assistant professors of biochemistry and center co-directors, are studying proteins involved in cancer and amyotrophic lateral sclerosis (ALS), respectively. "By understanding the 3-D structures of normal and mutant proteins, we can begin to understand how the mutant proteins function abnormally, which in turn provides the platform upon which to design therapies," said Dr. Hart, who directs the X-ray Crystallography Laboratory.
Development of novel therapeutic agents is under way through the researchers’ collaboration with colleagues in the San Antonio Cancer Institute, an NCI-designated Comprehensive Cancer Center and a partnership of the Health Science Center and the Cancer Therapy and Research Center. "The ability to visualize macromolecular structures at the molecular level is playing an increasingly important role in modern biomedical research, since such information often is the key to understanding how biological macromolecules, especially proteins, carry out their functions," said Dr. Hinck, who directs the Center for Biomolecular NMR Spectroscopy.
Other university scientists rely on a technique called "patch clamping," which monitors the activity of single molecules in real time. The molecules are crucial to body currents called ion channels. Since many human diseases are associated with or result directly from dysfunction of ion channels, these tools allow scientists to determine how these defects affect the body in control setting, said James D. Stockand, Ph.D., assistant professor of physiology. He studies ion channels and the effects of salt intake and high blood pressure on kidney disease.
Scientists have learned that mutations in the ion channels are responsible for kidney disease, hypertension, epilepsy, heart arrhythmias and cystic fibrosis. About 19 patch-clamp rigs worth an estimated $1.5 million will be used on campus once two new faculty members begin work by January 2003. Patch clamping is aptly named, for it involves electronically clamping cells in order to observe the activity of cellular molecules in isolation.
Fluorescence spectroscopy uses wavelengths of light to illuminate specific molecules, cells and genes. Tissues or cells have natural fluorescence, meaning they emit light on their own, but scientists often assist by shining a laser that intensifies the effect. "In essence, we make them glow," Dr. Frohlich said. "Many molecules that fluoresce, or glow, do so in a very characteristic way — a light fingerprint, if you will. It has been shown that very subtle changes in colors can indicate the difference between healthy and diseased cells. These types of instruments can be used to simplify biopsies, including for detecting skin cancers."
The genetics revolution sparked by the decoding of the human genetic blueprint, DNA, has spawned new technology as well. Scientists set up experiments to detect distinguishing characteristics in the genes of people with various diseases or syndromes. Some university faculty members utilize instruments found in the Advanced Nucleic Acids Core Facility in the Graduate School’s department of microbiology. "We have a robotic station for processing hundreds of genetic samples at one time," said Center Director Brian Wickes, Ph.D., assistant professor of microbiology.
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Another device called a "microarrayer" enables scientists to place tiny spots of DNA on specially treated microscope slides known as "chips." Each chip contains thousands or tens of thousands of genes. "Theoretically, you can place every single gene in an organism’s genome (an estimated 35,000) on a microscope slide," said Jan Vijg, Ph.D., director of the Human Genetics Program at the Sam and Ann Barshop Center for Longevity and Aging Studies, professor of physiology and research health scientist with the South Texas Veterans Health Care System.This is a major development in biomedicine, he said, because it enables a "big-picture" view of hundreds of genes involved in diseases such as cancer, kidney disease or neurodegenerative diseases. "As we look at more detailed information from individual subjects, we will see a rise of ‘personalized medicine’ based on their individual genomes," Dr. Vijg said.