| ||
| Vol. 22, No. 18 |
| October 1, 2000 |
|
Structural Biology - The Next Frontier By Dr. Bryant Boutwell The University of Texas - Houston Medical School
Look at the cover of many of the leading science journals and what do you see? Structure. Glorious three-dimensional, four-color structures of proteins and other essential gene products that seem to float off the page like invading starships from a distant galaxy. Thanks to enhanced imaging capabilities backed by the computer power and know-how to run sophisticated and highly complex modeling programs, scientists worldwide are now seeing for the first time the actual structures of the viruses, proteins, and other structures of life they have been pursuing. It is, say the experts, a major new frontier in biology that follows on the heels of man's success in mapping the entire human genome. From those genes come all life, all structure.
Using X-ray diffraction, high field nuclear magnetic resonance (NMR), and high resolution electron microscopy, UT-Houston Medical School faculty representing the combined strengths of the basic science departments, along with the Graduate School of Biomedical Sciences, and the Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), have reorganized the school's former Analytical Chemistry Center into the Structural Biology Research Center. Under the interim directorship of Dr. Rodney Kellems, chairman of biochemistry and molecular biology, significant investments are being made in state-of-the-art equipment and new faculty to make this Medical School the only institution in the Houston area with strong capabilities in all three imaging areas.
To put the field of structural biology into perspective, imagine trying to understand a car without ever seeing one. You have a chemist's notes on the properties of a tire, a fuzzy collection of snapshots showing what looks to be a steering wheel, a concept of a door with some kind of glass property that slides up and down, and some suggestions about how parts of a car might fit together. But to actually see a car would be the most helpful. For the first time you could actually confirm what you think you know and what you need to know. If your first observation is that there are four wheels, not one as some had insisted, then its obvious that visualizing the car's structure has already had a major impact on your understanding of how a car works, which in turn brings applied uses.
Teams of structural biologists are working to assimilate what we know about key biological structures, such as proteins or viruses, into a computer language that can take the best images available and construct the bigger picture of what it looks like. While that may sound easy enough, converting thousands of images into a completed three-dimensional structure is extremely complex work that only a few in the country are trained or equipped to do. The goals of structural biology are directed at understanding the fundamental architecture of the thousands of molecular machines whose coordinated activities allow cells to live.
"It's not only exciting work, it's essential," says Dr. Kellems. "There's much to be learned by visualizing structures of life at the molecular level. Our medical school is poised to take a leading role on the cutting edge of this field, thanks to the development of this new program."
Dr. Kellems notes that achieving a leading role in this field required the long-term vision and support of Dean Max Buja, along with collaborative working relationships involving all of the basic science including pathology and laboratory medicine. Departmental leadership across the school has worked with the Institute for Molecular Medicine and UT-Houston Health Science Center leadership, under the direction of Dr. Tom Burks, executive vice president for research and academic affairs, to pool existing faculty expertise and fund new core equipment that will provide imaging capabilities and newly recruited faculty expertise in the field of computational modeling. New equipment, including a new 600 MHz high field NMR instrument, and external collaborative agreements at the national level for rapid access to protein crystallography data, will put the Medical School on the leading edge of the structural biology field in the Texas Medical Center and region at large.
People instrumental in pooling expertise and resources to obtain new equipment and faculty positions for the new Structural Biology Research Center have been: Drs. Sam Kaplan, Microbiology and Molecular Genetics; Nobel Laureate Ferid Murad, Integrative Biology and Pharmacology; and Jack Byrne, Neurobiology and Anatomy. To complement and enhance the skills of existing faculty, three new faculty members joining the Center include Dr. Pawel Penczek, who has computational and imaging processing expertise, as well as Drs. C. S. Raman, specializing in protein crystallography, and Sudha Veeraraghavan, an expert in high field NMR spectroscopy. Additional new faculty will also be recruited in this area
The medical school faculty is already publishing some of the leading papers in the country related to this field. In June 2000, Dr. Hong Zhou, a pathology expert, was the lead author of a scientific article that illustrates and describes a computer model of a herpes virus capsid in unprecedented detail. Likewise, Drs. James Stoops, also in pathology, and Neal Waxham, a neurobiology and anatomy specialist, published a cover article in the May issue of The Journal of Biological Chemistry, on the structural organization of calcium/calmodulin-dependent protein kinase IIa. Dr. Penczek was recently featured in Cell for important work describing the structure of ribosomes at high resolution.
Members of the advisory committee who have worked tirelessly in recent years, with the support of Dean Buja, to organize this important program include Drs. Kellems, William Dowhan, John Putkey, Ponnada Narayana, Carmen Dessauer, John Spudich, and James Stoops.
©2006 Texas Medical Center E-Mail: tmcinfo@texmedctr.tmc.edu URL: http://www.tmc.edu/tmcnews/10_01_00/page_10.html |
