Nanomedicine: Solving problems at the smallest level
Wah Chiu, PhD, minces no words. He is a problem solver. His approach to scientific discovery is more like that of a hurdler, who overcomes a series of barriers, than the traditional biologist whose research is driven by hypothesis.
"It is like going to the moon," he said. "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, he 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. His is one of four such Nanomedicine Development Center funded through the NIH. Establishment for his Center came from an NIH Roadmap grant. The NIH Roadmap is the brainchild of NIH Director Elias A. Zerhouni, MD.
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, PhD, associate professor of Biological Sciences and BioX Program 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 can we design the chamber (in which they are folded) differently so that we can fold any protein we want." he 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 problem 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, based at BCM, is part of the National Institutes of Health's Roadmap Initiative designed to encourage biomedical investigators to take on challenging problems and solve them with unusual approaches.
"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, under 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 with engineers, computer scientists and biomedical investigators.
Paul A. Sieving, MD, director of the National Eye Institute, said, "These Nanomedicine Development Centers will gather extensive information on the intricate operations of molecular structures, processes, and networks used by living cells. This will help us understand the rules of biological design and will enable scientists to build synthetic biological tools at the nano scale to correct defects in unhealthy cells. Ultimately, we anticipate that these tools will find application for a wide range of tissues and diseases."
"I have been lucky to have collaborators who are cooperative, collaborative and very smart," said Chiu. "I think with we have come up with some neat and novel ideas of how to integrate the expertise.
"The culture of thinking is very different," he said.
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 Sciencesthe 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 MD 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.