Imagine waking to a bright, sunny day, but not really being able to see. Some people go their whole lives without witnessing that vivid red ball from their youth or the facial features of a loved one. Kristina Narfström, a veterinary ophthalmologist at the University of Missouri, is doing research that promises to provide some light at the end of the tunnel.
With all the different projects Professor Chi-Ren Shyu has on his proverbial plate, it's hard to imagine he has any time to sleep. Yet with easy finesse and exuberance, Shyu describes just a few of his ongoing "joyful and rewarding" research initiatives, ranging from biomedical and geospatial informatics to computer imaging of medical images. Not surprisingly, Shyu has gained a well-earned reputation for his collaborative work. Although diverse, what these research interests share is the effort to create large-scale, fast, and multidimensional databases.
Comparing parts of the HIV virus to the parts of a military missile, Johnson explains the various components of the virus. A complete understanding of the HIV structure and life cycle will help scientists develop new treatments for the disease. “It’s pretty remarkable, and there’s clearly a lot about it that we don’t yet know,” Johnson admits. Most of his research revolves around the protein Gag.
Narfström discusses various treatment measures for blindness. The prevention of photoreceptor death, she says, can be treated with different proteins and vitamins, or new cells may be inserted in the retina to replace the dying cells.
Genetic transfer can be used to replace dead photoreceptor cells. Narfström employs this method to correct protein defects in the eyes. The procedure involves injecting a construct – a vehicle that brings the protein the correct DNA – into the retina cell. The construct is then transported into the nucleus, where it is translated to make the correct protein.
As a graduate student in the Department of Molecular Microbiology and Immunology in MU’s School of Medicine, Brian Bostick works with professor Dongsheng Duan in the area of gene therapy. Bostick’s research seeks to develop a treatment for the most common form of muscular dystrophy, Duchenne muscular dystrophy, in which patients are missing a gene called dystrophin. Gene therapy involves the replacement or addition of a missing gene. Bostick’s research involves inserting this gene into a virus and then injecting it into an animal body. “Just by using the normal properties of how a virus works,” Bostick explains, “we can actually replace genes that are missing.”
Bostick’s research focuses specifically on the heart disease associated with Duchenne muscular dystrophy, where a gradual weakening of the muscles occurs—starting with the larger muscles—so that patients have trouble breathing by the time they are teenagers. For a long time, such respiratory problems had been the major cause of death among DMD patients, but doctors are now better able to treat the respiratory disease. Because the heart muscle also needs dystrophin to function properly, heart disease worsens as these patients live longer. Heart disease, in fact, is now a major cause of death among DMD patients, a problem that Bostick and his mentor Duan seek to address by developing a heart disease model in mice.
Bostick offers a quick tour of Duan’s laboratory, illustrating the processes involved in several research projects—from the mouse treadmill to the surgical area and where the mice are kept under observation. Delicately selecting several mice, Bostick shows examples of a normal mouse, one with MD, and another with MD undergoing gene replacement therapy. The difference, in both size and activity, between the untreated mouse and the one given gene therapy is remarkable and promising for future applications of this research.
A graduate student in the School of Medicine’s Department of Molecular Microbiology and Immunology, Erica Racen works with professor Karen Bennett to study germline development in a small worm known as Caenorhabditis elegans. The germline are the cells that go on to become the next generation of the eggs or the sperm. “Our lab studies four proteins which are important for that development,” Racen explains. “When one of those proteins is missing, the worm becomes sterile.” Racen describes the worm in question, which is only one millimeter in length. Because it has a large germline, it is a good organism to study germline development.
“When I first started studying the protein GLH-1,” recounts Racen, “I knew it was important for fertility, but I did not know why. So I started to look at what things are different when GLH is missing. I found a relationship to the protein Dicer, that when GLH-1 was missing, so was Dicer. I also found that when Dicer was missing, so was RNA.” Trying to understand this relationship, Racen has conducted a series of experiments. She describes an actual experiment, one that involves mutants in which the gene has been knocked out or uses the process of “RNA interference” (injecting double-stranded RNAs into the worm, so that in the next generation those proteins are not produced). In this manner, Racen is able to study different genes in the worm.
Racen describes “a typical day in the lab,” providing a tour of Karen Bennett’s lab and showing some of the equipment used for her experiments. A typical day begins at sunrise when Racen plans her experiments, and will likely involve grinding worms to extract the cell lysate and problem solving with colleagues doing similar experiments.
Racen refers to her research as basic science. While the protein she works with is also found in humans, as of now there are few direct applications of this kind of research. Racen explains, however, “The more we learn about basic science, it will help us develop better treatments down the road. If we can understand how an egg develops from the very beginning, including all the proteins involved, we will have a better understanding of how to treat it.”
Demonstration by Shyu of the protein database.
The new database that offers real time, high-accuracy searches for researchers.