Biophysicist in Profile

Ian Thorpe

Since childhood, Ian Thorpe, Assistant Professor in the Department of Chemistry & Biochemistry at the University of Maryland, Baltimore County, has been fascinated by science—not just by doing science, but by its implications. “I enjoyed reading science fiction, with its visions of future possibilities,” he says. “I resolved to play a role in making some of these visions reality.” Thorpe’s parents, particularly his father, a mechanical engineer, fostered a love of physics and math in their children, and encouraged Thorpe’s interest in science. Genetic engineering enthralled Thorpe, and he realized that he could use science to make the world in which he lived a better place. “Living organisms are exceedingly complex,” says Thorpe, “and it may be possible to harness some of this complexity to help solve many of the world’s problems, including famine, disease, and pollution.”

Fueled by enthusiasm, Thorpe began to build a foundation of knowledge for a career as a genetic engineer. As soon as he entered Belair High School in Mandeville, Jamaica, he zeroed in on biochemistry, math, and physics and continued this focus through his Sixth Form studies at Wolmer’s Boys’ School in Kingston, Jamaica. Thorpe was a tenacious, driven student, striving for two distinct goals. “The first of these was to rack up the necessary research experience to make me an attractive candidate for graduate programs,” he says. “The second was to identify specific areas that I enjoyed working in.” Accomplishing the former was second nature to Thorpe; he was bright, focused, and eager to learn. Accomplishing the latter, however, presented a challenge. “I disliked having to schedule my life around my experiments and yearned for a molecular level understanding of the projects that was not always available,” he recalls. Finally, one of his last undergraduate research projects brought a breakthrough. A Biochemistry/Molecular Biology and Chemistry major at the University of Miami, Thorpe was studying human retinol binding protein in Keith Brew’s lab, trying to determine whether the protein could be used to transport artificial hemoglobin. Significant protein aggregation made recombinant expression of the protein difficult, and the yield was low. Determined to find a solution, Thorpe tried applying computation to the project. He worked with Jeffrey Evanseck in the Chemistry Department to develop a molecular model of the protein. “That is when something finally clicked: this was what I enjoyed doing!” he says. “It was fascinating to try to understand, at the molecular level, the physical principles governing observations made in the laboratory.”

After graduation, Thorpe embarked on a new challenge: transitioning from undergraduate to graduate school. “Early on in my undergraduate career I had become highly specialized—probably overly so—with respect to my academic training, with heavy emphasis on biochemistry and molecular biology,” he says. “However, the switch to computational biophysics necessitated preparation in other areas such as mathematics and physics that were not fresh in my mind by the time I entered graduate school.” With enormous effort, Thorpe got himself up to speed and joined the group headed by Charles L. Brooks, III at The Scripps Research Institute, investigating the role of protein motions in modulating catalytic activity in enzymes as well as the molecular mechanisms that underlie the maturation of recognition in antibodies. “As a graduate student, Ian was excellent,” says Brooks. “He continually challenged me, as he should have done, and together we worked through approaches to many scientific questions.” Now, Thorpe advises students not to pigeonhole themselves into a scientific area. “It is necessary to become an expert in a specific field to further your career,” he says, “but one must also maintain an appreciation for diverse scientific areas in order to carry out the most relevant and impactful research.”

With a doctorate under his belt, Thorpe took a postdoctoral position in Gregory Voth’s group at the University of Utah. There, Thorpe deepened his own research perspective by applying the group’s multiscale coarse-graining methodology to study peptides, aiming to ultimately apply the method to proteins. At the same time, a knack for mentoring began to emerge in Thorpe. “While in my group, Ian helped to mentor two graduate students and one undergraduate, and I think he has a special talent in that regard,” says Voth. “In each case, his interactions with these students resulted in high-quality research and ultimately led to excellent publications.” Ron Hills, Thorpe’s fellow graduate student and fellow postdoc and current Assistant Professor at the University of New England College of Pharmacy, also benefitted from Thorpe’s advice. “As a peer mentor, Ian maintained a balance of rigor, pragmatism, insight, and friendship,” Hills says. “He laid out his successes and challenges in the development of coarse-grained protein modeling methods, and what were the next steps. Research in my lab today is continually guided by the lessons he taught me.” Mentoring comes naturally to Thorpe, and he views it as a rewarding aspect of his job. “I enjoy being able to continually learn new things as well as work with young scientists to help them achieve their career and professional goals,” he says.

Thope’s own lab is currently focused on understanding the process of allosteric inhibition in the RNA polymerase from hepatitis C virus (HCV) in an effort to find a treatment for the more than 200 million people worldwide infected with HCV. “The RNA polymerase of HCV has emerged as a useful target for therapeutics due to its crucial role in viral replication,” says Thorpe. “Certain ligands act in an allosteric manner and inhibit the enzyme despite being bound up to 30 Å from the enzyme active site. We want to understand the molecular properties that allow these inhibitors to display such effects.”

Thorpe’s group often teams up with experimentalists to enrich their perspective, and to explore connections between their theoretical results and experimentalists’ observations. One of the sources for finding these teammates is the Biophysical Society Annual Meeting. “I recently identified a possible experimental collaborator by attending a talk given by one of his postdoctoral associates,” says Thorpe. “In addition, I have met other researchers working on projects similar to my own, allowing me to compare and contrast our research findings.”

Though he did not end up in genetic engineering, Thorpe is still using his chosen research area to impact future possibilities. “Eventually, I predict that degrees in biophysics will become as common as degrees in biochemistry are today,” he says. “I see myself playing an important role in this process by finding new ways to bridge the fields of experimental, computational, and theoretical biophysics.”

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December 2011 Table of Contents