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Of Mice and MenTechnology reveals new details about the brains of animals and humansby Ruth SoRelle, M.P.H.
The flower is called a tachibana, and it is the family crest of Pautler's mother, who is from Japan. The "tail" is actually an axon - the long fiber that extends from a neuron or nerve cell that enables the transmission of signal or information to another neuron. Family and science play a large role in the background and in the future of this scientist whose childhood interests resulted in her developing, as a graduate student, a new method of viewing the actions of nerves in living animals using manganese and magnetic resonance imaging (MRI). Dubbed MEMRI (manganese-enhanced MRI) by Pautler, the technique gives scientists unprecedented access to the inner workings of animal brains, and could some day provide important information about diseases, such as Alzheimer's, that attack the brain.
Science has long been a critical part of her life. At age 13 she was helping in her dad's lab and noticed that the rat pups crawled toward the shavings from their mom's cage, attracted to the odorants their mother generated while she was in cycle. "My interest in olfaction (the sense of smell) stems from that," she said. When she was a graduate student at Carnegie-Mellon University Pittsburgh, she decided to do functional magnetic resonance scanning of the sense of smell in mice. The problem was finding a way to trace the signal on the scan. Her scientist father had always advised that she read the scientific literature frequently and carefully. Her practice of following that advice daily gave her a clue. Manganese, a metal element believed to be paramagnetic (attracted to magnetic fields), has an added bonus in the properties that make it similar to calcium. One study indicated that manganese can get into the brain through the nerve cells governing the sense of smell. If all this were true, it would prove ideal for the MRI studies Pautler planned. Proving that took time. "It took a couple of months at least," she said. "The first time I got it to work was at 1 a.m. and I was the only one there. I was so happy that I put Beethoven's "Ode to Joy" on the stereo and ran and up and down the halls." Tissues where manganese collects shine bright on MRI images. However, the bright images provide more than information about the anatomy of brain. They also enable researchers to measure the size of connections between neurons and the structures of the nerve cells involved. "What's really nice is we can look at the dynamics of the nerve cell and its function," she said. Because the manganese enters the neurons through channels usually reserved for calcium, she and her colleagues can directly measure how fast something can be transported down the length of the axon. "That's how many important substances get transported," said Pautler. "It is an important process. No one has ever measured this in a live animal before. Here we can use manganese as a probe to measure the speed of this process and we can do it repeatedly." When she measures axonal transport in a mouse that has Alzheimer's disease, she sees a reduction in the rate of transport, a phenomenon she terms interesting and plans to study further. Manganese also enables her to look at the cell from a biochemical aspect and to view it under sophisticated microscopes. The MRI she is currently using contains a chamber specifically designed for mice and small rats. It is connected to a special sedation unit and contains headgear to hold the mouse still and a water blanket to keep the animal warm during the procedure. Soon, she said, she anticipates delivery of another MRI that will enable her to provide others at BCM with the opportunity to do scans on their own animals. Establishing that core facility is high on her agenda, and she and programmers are already hard at work. She proudly displays a computer image that shows a mouse's heart beating. Slowed down on the video display, it is a graphic demonstration of the imaging capabilities of her facility. A mouse heart beats on average 600 times a minute and is no bigger than a human fingernail. However, the image on the computer enables one to pick out the heart's four chambers and even valves with relative ease. Another image is the three-dimensional representation of an embryo's skeleton, designed to help with work looking at mutations in the animal. A click of the computer mouse can flip the image around, giving the researcher a full-dimensional view of the animal. The ability to provide such clear images of such tiny organisms is part of the value of the MRI, and Pautler hopes to make such studies readily available to others at the College. Another aspect of her job also gives her great joy - teaching. Already, she has attracted an M.D./Ph.D. student - Mitchell Deshazer. His enthusiasm for her laboratory combined with his desire to be part of the new Ph.D. program in translational biology and molecular medicine has him "popping ideas out like popcorn," said Pautler. He agrees with Dr. Peter Traber, president and CEO of BCM, that research is actually a social contract between the scientist and society. "I like the idea of turning basic science into things that are practical and applicable to disease," said Deshazer. "A lot of the things we do at Baylor College of Medicine involve developing tools. But those tools are more than an academic enterprise. You can publish 100 papers and not help a single patient." He hopes the work he does with Pautler has a direct effect on diseases such as Alzheimer's, with which he has personal experience through family members who have had the disease. Solving the problem of Alzheimer's involves more than developing drugs, however. If a pill that cured it were found today, doctors would not know to whom they should give it. "There is no good way to diagnose the disease (in living patients) right now," he said. "The gold standard of diagnosis is autopsy." He hopes his work will help advance diagnosis to the point that it is possible early on. He thinks he will develop the tools to do that working with Pautler. Pautler hopes so as well. Deshazer is just the beginning in her teaching career. She hopes to be able to provide many more students with the tools they need to do important research. It is all part of building her scientific family and creating a biomedical legacy. It is an unusual point of view in a young scientist, but Pautler is not always constrained by convention. Trained in classical piano and a banjo player by choice, Pautler sees the world from her own perspective. When the BCM architect asked her if she would like a design on the floor of her lab, it immediately piqued her interest. While she knew he probably wanted to know if she wanted checks or zigzags, she immediately described her neuron and how it would work in the lab. The notion intrigued him, and he found a way to give her what she wanted. Her design marks the lab as uniquely hers. It is a clear melding of the art and science she loves. Her ancestors were samurais, and in her own way, Pautler herself is going into battle - against diseases that attack the brain, some of the most fearsome enemies ever confronted by humanity. |
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Volume 1, Issue 2, Summer 2005 |
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| Last modified: October 10, 2008 |
The stylized flower on the outer wall and the purple tail exuding from under the frosted glass door of Dr. Robia G. Pautler's laboratory provide clues to both what is going on inside and the nature of the scientist who directs the work.
Her prowess sparked interest around the world, and when Baylor College of Medicine was looking for someone in her field, her name was the one that kept cropping up. The scientific prospects of BCM intrigued her, and she accepted a post as Assistant Professor in the Department of Molecular Physiology & Biophysics.