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Research Newsletter-Spring/Summer 2006

The Human Side of Research



Kristine Robinson
LPI Graduate Fellow



At the age of eighteen I began to dream of opening my own flower shop or becoming an engineer. However, the course work in business or physics required to accomplish these goals either did not interest me or was a struggle. Surprisingly, when other students groaned at their test scores in chemistry class, I sat quietly in shock when I got nearly perfect scores. I was fascinated by chemical theory and atomic structure, so I followed my aptitude and completed my bachelor's degree in chemistry. I always knew I would someday want to apply that knowledge in the medical field and, hopefully, make a significant contribution in disease research. Changing my focus from chemistry to biochemistry in graduate school was the first natural step toward accomplishing my goal. Oregon State University offered a unique opportunity to work in an atmosphere more focused on biophysics and the chemistry of biochemistry. The Department of Biochemistry is also linked to the Linus Pauling Institute, which has the attractive aspect of disease-oriented research. I was introduced to LPI Principal Investigator Dr. Joe Beckman, whose laboratory focuses on Lou Gehrig's disease. My dreams of working on disease were starting to become a reality.

Working in Dr. Beckman's lab allowed me to find a way to apply chemistry to disease by investigating the role of free radicals in neurodegeneration. Recent breakthroughs in scientific techniques have revealed the significant role free radicals play in disease progression, establishing a new frontier in free radical research—a perfect fit for my background.

The research on Lou Gehrig's disease (also called amyotrophic lateral sclerosis, or ALS) in Dr. Beckman's lab focuses on the mechanism that causes the progressive death of motor neurons. ALS is a fatal neurodegenerative disease, and the cause remains elusive, as does a cure. Dr. Beckman observed an increased production of free radicals in ALS and asked the question, "Did free radicals kill Lou Gehrig?" My research in the lab has been on two free radicals, nitric oxide (NO) and superoxide (O2.-), and how they can combine to create a toxin, peroxynitrite (ONOO-), which we believe could be responsible for killing motor neurons (see illustration below). This past year, my research has been specifically focused on detecting the peroxynitrite precursor, superoxide. Unfortunately, the most popular fluorescent moiety used to detect superoxide, dihydroethidium, is not actually specific for superoxide at all.



Publications from the mid-1980's demonstrating this lack of specificity seem to have been forgotten. I was asked to characterize the chemistry of a new derivative of dihydroethidium, which might serve as a more specific tool. To do this, I learned several techniques, such as mass spectrometry, nuclear magnetic resonance spectroscopy (NMR), culturing primary neuronal cell lines, imaging those cells by confocal microscopy, and isolating mitochondria from rat hearts to measure superoxide generation. While analyzing this new probe, I found a simple fluorometric method that provides the specific detection of superoxide. I now intend to apply this technique of superoxide detection to motor neurons in culture and test for increased superoxide generation in an ALS animal model. Moreover, I can use this method to test agents, such as metal chelators, that might inhibit the increased generation of superoxide in ALS.

These investigations have also emphasized to me the importance of collaboration in the international scientific community. I have worked with scientists from Uruguay on the isolation of motor neurons and with a scientist from England, Dr. Michael P. Murphy, on the use of electrochemical probes. Attendance at international meetings, provided for by my LPI graduate fellowship, has been a major part of facilitating these connections. Presenting research at these meetings has also helped me discover the enjoyment of communicating my research to other people. I intend to pursue a research career applying my background in chemistry to the question of free radicals in neurodegeneration. I am also excited by the prospect of teaching biochemistry.

One valuable lesson I have learned while working for Joe Beckman is the importance of research to patients. Joe does an excellent job of educating ALS patients not only by giving lectures in hospitals and elsewhere, but also by inviting patients to visit our lab. Moreover, I've watched him take time for the seemingly smaller tasks, such as making driving arrangements for patients to attend ALS meetings. Developing and maintaining contact with patients has also become a very important goal for my research career. During the past few years I was able to volunteer to help with an ALS patient. I first met "Bob" when Joe had invited him to come visit our lab. Over the period of one year, Bob's condition had deteriorated. He was able to visit our lab, but then he became immobilized at home. We volunteered to do jobs at his home that he could no longer do, like pruning trees in his orchard and hanging up a birdhouse by the bedroom window. I also remember a very sad visit with Bob's wife at his funeral—another vivid reminder of the tragedy of ALS. I was the only member of the lab at the funeral, and I felt like a representative from the group that could have potentially prevented this loss but had not yet found a way to do so.

My experience with Bob taught me that the work we do is very important to real people. Combining academic research with human affairs completes my dream of trying to make a difference by working on neurodegenerative diseases.

Last updated June, 2006