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Unfolding the Tiniest Problemsby Ruth SoRelle, M.P.H.
"Those people had a lot of engineering problems to deal with. If I want to go to the moon, I want to know how we are going to do it and what kind of hurdles we have to jump. I want to organize a team to accomplish this." In this case, Chiu is forming the Center for Protein Folding Machinery. A recent multi-million dollar grant from the National Institutes of Health will make it possible for his work to go ahead as one of four Nanomedicine Development Centers funded through the NIH via the Roadmap initiative—the brainchild of NIH Director Elias A. Zerhouni, M.D. The NIH Roadmap identifies the most compelling opportunities for taking medical progress into the next century. The three main areas include: new pathways to discovery, research teams of the future, and re-engineering the clinical research enterprise. Nanomedicine plays an important part in the first, and Chiu's vision of how to attack the problem fits well the aims of the other two. By applying his problem-solving approach, Chiu hopes to discover how proteins go from a linear, non-functional form to the three-dimensional shapes that allow them to achieve their biological purposes. It is a fundamental issue in biomedicine that can, eventually, be applied to a host of biotechnological problems and to diseases as wide-ranging as Alzheimer's, cancer and cystic fibrosis. Bringing together researchers from a variety of disciplines and different institutions, he hopes to explain the working of molecular chaperones—biological machines that oversee the proper shaping of protein molecules. If the consortium can discover how this biological machine works and what happens when it fails in its task, it could open new vistas in understanding diseases related to misfolded proteins and open doors to correcting the problems. His co-director, Judith Frydman, Ph.D., associate professor of biological sciences at Stanford University in California, will provide key input into the work from a different point of view. "Once we understand how one or two proteins fold, then we can design the chamber (in which they are folded) differently so that we can fold any protein we want." Chiu said. "Think about the biotech company that wants to make a protein. Often the hurdle in making a protein is to get it folded correctly. If we understand the protein folding machinery in terms of how it is designed and how it works, then we could modify it so it could fold other proteins of interest." It is not the kind of experimental challenge that Chiu could tackle alone, nor was he interested in doing so. "We need to treat this as a problem. This is a problem to be fixed," he said. "How do we approach this problem? I have only limited knowledge. We need to find people with complementary expertise, those who have different experimental and computational techniques. "That is why I have formed a team of 13 investigators," he said. The center is based at BCM but has virtual connections around the nation. "If I do what I know best, I won't solve this problem by taking pictures in the high resolution cryoelectron microscope," he said. "My approach alone is inadequate." Nanomedicine, the discipline to which this work belongs, is the study of the very small. The roadmap initiative encourages people to look at problems in new ways—to think outside the box in popular parlance. "It turns out that actually very few people can do that, including ourselves," he said. To encourage this, the NIH fosters partnership among engineers, computer scientists and biomedical investigators. "I have been lucky to have collaborators who are cooperative, collaborative and very smart," said Chiu. "I think we have come up with some neat and novel ideas of how to integrate the expertise. The culture of thinking is very different." Others involved in the Center include: Drs. W.E. Moerner, professor of chemistry, Vijay Pande, associate professor of chemistry, Michael Levitt, professor of structural biology, and Scott L. Delp, chair of bioengineering, Stanford University; Drs. David Gossard, professor of mechanical engineering, and Jonathan King, professor of biology, Massachusetts Institute of Technology; Drs. Tanja Kortemme, assistant professor of pharmaceutical chemistry, and Andrei Sali, professor and vice chair, department of biopharmaceutical sciences, University of California-San Francisco; Drs.Steven Chu, director, and Paul Adams, staff scientist, Lawrence Berkeley National Laboratory; Dr. Eric Jonasch, assistant professor of oncology, The University of Texas M.D. Anderson Cancer Center; and Drs. Steven Ludtke, assistant professor of biochemistry and molecular biology, and Huda Y. Zoghbi, professor of molecular and human genetics and pediatrics, BCM. |
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Volume 2, Issue 1, Spring 2006 |
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| Last modified: April 10, 2006 |
"It is like going to the moon," said Wah Chiu, Ph.D., BCM professor of biochemistry.