University Of Arkansas Wins $9.6 Million NIH Grant To Establish Center For Protein Structure And Function

FAYETTEVILLE, Ark. - The University of Arkansas has received a $9.6 million grant from the National Institutes of Health to harness the wealth of the human genome by studying the compounds that DNA produces - proteins.

With the funds, the largest competitive research grant ever received at the U of A, the University will establish the Center for Protein Structure and Function, which will support five multi-disciplinary, collaborative research projects. The projects will involve seven junior faculty, eight senior faculty and four new faculty in chemistry and biological sciences at the University of Arkansas, and three faculty in the biochemistry and molecular biology department at the University of Arkansas for Medical Sciences.

"This grant will enable researchers to contribute a great deal more to biomedical research," said Chancellor John A. White. "It will also attract the attention of superlative faculty, staff and students who will come to the University of Arkansas and contribute to its intellectual growth."

The award will support financially eight junior faculty and five new faculty, with the senior faculty providing expertise and advice.

"Nearly all the faculty have current, ongoing grants in their research areas, but this will take them to another level," said Frank Millett, University Professor of chemistry and biochemistry and principal investigator for the grant.

The center was one of 19 established by NIH this year. Other institutions awarded funds include the University of Kansas Center for Research, Inc. at Lawrence; the University of Nebraska at Lincoln; the Oklahoma University Health Science Center in Oklahoma City and Brown University.

The Human Genome Project has yielded the sequences of more than 100,000 genes that code for proteins. The nucleotide sequence of any genome can be readily translated into the amino acid sequence of the corresponding protein, but little is known about the structure and function of many of those proteins. This gap in knowledge is critical because proteins do nearly all the work in the cells of our bodies, ranging from brain function and nerve transmission to metabolic energy production and muscular contraction. Moreover, most diseases are associated with defects in protein function.

The 22 researchers involved with this project all focus on some aspect of protein structure and function. The center will build upon the strong faculty expertise already present at the U of A in X-ray crystallography, solid-state NMR mass spectrometry, computational chemistry, kinetic analysis, peptide and drug design and chemical synthesis. These methods help researchers learn more about protein structures, shapes, and their interactions with other molecules. T

he center will strengthen collaboration between investigators and allow them to develop promising new approaches to biomedical research in protein structure and function and drug discovery.

In the first research project, Joshua Sakon and Mack Ivey will develop molecular inhibitors to combat Clostridium infections, which are a serious problem in hospitals, particularly among elderly patients. Denise Greathouse will study cation transport across biological membranes, a process that plays an essential role in many biological functions, including nerve transmission in brain and muscle.

In the second project, Ken Turnbull and Kevin Raney will seek novel strategies to treat the Hepatitis C virus, which threatens the health of many in Arkansas and across the nation. Matt McIntosh will work on the discovery of new anti-cancer drugs with fewer side effects and a wider spectrum of activity.

In the third project, Ralph Henry and Joshua Sakon will attempt to locate and understand protein-targeting sequences, the "postal codes" cells use to send a protein to its correct location.

In the fourth project, Wes Stites will address the question of what allows a protein to fold into a specific shape, with the ultimate goal of predicting a protein’s structure from its amino acid sequence.

And in the fifth project, Mack Ivey, Frank Millett, and Bill Durham will examine the mechanism of oxidative phosphorylation, a fundamental process in biological energy transformation that, when disrupted, leads to degenerative diseases and aging.

The U of A will also purchase a 700 MegaHertz nuclear magnetic resonance spectrometer, which will be used to determine the complete three-dimensional structure of proteins, as well as their internal motions.

The center also will build upon the X-ray crystallography laboratory directed by Joshua Sakon and Wes Stites, the NMR laboratory directed by Jim Hinton and the Arkansas High Performance Mass Spectrometry Facility directed by Charles Wilkins.

This program has the potential to substantially expand state-of-the-art structural protein studies in Arkansas, according the NIH committee that reviewed the proposal.

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Center for Protein Structure and Function

Director

• Francis S. Millett, University Professor; chemistry and biochemistry

Co-Director

• Roger Koeppe, University Professor; chemistry and biochemistry

Junior investigators include:

• Denise Greathouse, Research Assistant Professor, chemistry and biochemistry
• Ralph Henry, Assistant Professor, biological sciences
• D.Mack Ivey, Associate Professor, biological sciences
• Matt McIntosh, Assistant Professor, chemistry and biochemistry
• Kevin D. Raney, Assistant Professor, biochemistry and molecular biology, UAMS
• Joshua Sakon, Assistant Professor, chemistry and biochemistry
• Wes Stites, Associate Professor, chemistry and biochemistry
• Ken Turnbull, Assistant Profesor, chemistry and biochemistry

Senior Investigators include:

• Dan Davis, Professor, chemistry and biochemistry
• Bill Durham, Professor, chemistry and biochemistry
• Alan D. Elbein, Professor and Chair, biochemistry and molecular biology, UAMS
• James Hinton, University Professor, chemistry and biochemistry
• Peter Pulay, Distinguished Professor, chemistry and biochemistry
• Lothar Schafer, Distinguished Professor, chemistry and biochemistry
• Charles L. Wilkins, Distinguished Professor, chemistry and biochemistry

New investigators will include researchers with expertise in the following fields:

NMR spectroscopy of protein structure, chemistry and biochemistry

Drug design using combinatorial chemistry, chemistry and biochemistry

Protein chemistry, biochemistry and molecular biology, UAMS

Membrane protein structure and function, biological sciences

Receptor-ligand interactions in cell signaling, biological sciences