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What does the Hauptman-Woodward Institute do?
The Hauptman-Woodward Medical Research Institute (HWI) is an independent, not-for-profit, biomedical research facility located in the heart of downtown Buffalo's medical campus. For half a century, HWI scientists have been committed to improving human health through study, at a molecular level, of the causes and potential cures of many diseases. In contrast to clinical research, the focus of Hauptman-Woodward’s basic research is to determine the structures of individual substances such as proteins that play a role in the development of specific diseases. This research explores questions like the following: What is the three-dimensional shape of a particular protein molecule? How does this structure dictate the biological function in a cell?  How and with what does this protein interact? What structural alterations lead to the development of disease?

Inspired by Nobel Laureate Herbert Hauptman, HWI scientists use the techniques of molecular biology, biochemistry, and crystallography to answer these questions. The results of their investigations provide the starting point for better drug design. In addition, other current research at HWI seeks to improve the crystallographic methods used for molecular structure determination by scientists worldwide.

What is Crystallography?
Crystallography is the study of the arrangements of atoms within a molecule. The science of crystallography allows the determination of precise atomic positions of any molecule that can be persuaded to form a crystal. In a crystal, atoms are arranged in an orderly and repetitive fashion. The repeating unit can contain one atom, as the repeating carbon atoms in a diamond, or tens of thousands of atoms in the large protein crystals studied at HWI.

In a crystallographic experiment, a single crystal of a purified substance such as a protein is irradiated, typically with X-rays. The incident radiation is scattered to produce a diffraction pattern, and a complex mathematical analysis of the diffraction data (a process known as "solving" the structure) will determine the shape and atomic arrangement of the molecules comprising the crystal.

Crystallogaphy can, therefore, be broadly thought of as the development of techniques, concepts, and methods that use crystals to determine molecular structure.

What is structural biology?
Structural biology is the study of the biological world with a particular emphasis on the use of atomic resolution structural information to further our understanding of biological phenomena.  Structural biology is closely associated with techniques used to obtain structural information, including X-ray crystallography and NMR spectroscopy.  However, these techniques are not used to the exclusion of other approaches, including biochemical and cell biological assays, but, rather, serve to complement the arsenal of analytical tools available to the biologist.

What information is derived from structures?
Once the structure has been solved, molecular models can be constructed and examined for insight into how the protein molecules function, what might be happening when disease occurs, and what compounds might be designed as drugs to modify activity.

What diseases are being studied at HWI?
HWI scientists work diligently to contribute to the body of knowledge that underlies medical practice. The impact of their basic research studies is far reaching. The development of new therapies and cures for devastating diseases often depends on the kind of molecular-level information that is the product of the structural biology research conducted at HWI and similar institutions. Typically, this research involves the study of protein molecules, especially the type of proteins that function as biological catalysts and are known as enzymes.  Diseases to which the studies ongoing at HWI apply include:  AIDS, arthritis, breast cancer, other cancers, macular degeneration, melanoma, polycystic kidney disease, and thyroid disorders.  Additional projects at HWI focus on the viral and bacterial pathogens that cause many infectious diseases.

How has the work at HWI been used by other scientists?
HWI has made significant contributions to the development of methods for crystallography and structural biology.  Thousands of scientists have used the mathematical and computational algorithms devised at HWI in the determination of crystallographic structures. Additionally, many scientists are currently sending proteins to HWI to obtain lead conditions for the generation of crystals of the proteins that they study. Finally, the structures determined at HWI, and the biochemical analysis of these structures, are published in journal articles and deposited in databases where other scientists can access these structures and the insights they provide.

What is the difference between basic research and clinical research?
Basic research is the study of the fundamental processes of nature.  It answers questions such as "How does something work?" or "What are the principles that govern a certain process?"  In its purest form, basic research has no goal except the acquisition of new knowledge. This information provides the foundation for all advances in technology.

These basic research results are used in applied research.  In the medical area, applied research is called clinical research.  Clinical research, for example, might take the basic information about how tumor cells grow and use that to develop a new anticancer agent.

How is the research at HWI supported?
Work at HWI is primarily supported by grants from federal agencies such as the National Institutes of Health and the National Science Foundation. These Federal dollars support innovative and promising research, for which preliminary results have been obtained that suggest the research will be successful and lead to significant improvements in human health. Because these federal agencies will not support preliminary experiments, donations from private individuals and philanthropic organizations are used to support start-up funds for new investigators and pilot projects for established scientists who initiate new projects.

What is the relationship between HWI and UB?
In January 2001, HWI and the University at Buffalo (UB) reached a historic collaborative agreement, which resulted in the formation of the UB Department of Structural Biology. The department is located at HWI, uses HWI facilities, and is staffed by HWI scientists.  The Department of Structural Biology currently has ten graduate students who are pursuing a Ph.D. degree in Structural Biology, and six post-doctoral research scientists, all of whom are being trained in the latest techniques in Structural Biology.  Also as part of its educational mission, HWI houses a summer research program where 10-20 undergraduate and high school students take part in the research at HWI.

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