David Eisenberg to present Hans Neurath Lecture Friday

Abnormal protein accumulations characterize many disorders — cataracts, Alzheimer’s, Parkinson’s, and Lou Gehrig’s diseases. Protein aggregates can compromise the viability of affected cells. How protein molecules engage in fatal attractions and entangling alliances is a key area of research for this year’s Hans Neurath Lecturer. The lectureship is named for the founding chair of the Department of Biochemistry (see profile).

Eisenberg

Dr. David Eisenberg, professor of chemistry and biochemistry at the University of California-Los Angeles, studies protein-protein interactions through X-ray crystallography and advanced computing methods. He leads the lab that discovered a novel mode of protein association called “three-dimensional domain swapping.” In this mode, two protein molecules interact by exchanging important functional sections. Eisenberg’s current experiments are aimed at learning if 3-D domain swapping can account for pathogenic protein aggregates such as amyloids. Amyloid deposits are found in the brains of Alzheimer’s victims and in the diabetic pancreas.

Eisenberg’s investigations into protein molecule interactions grow from his attempts to study a central question of biochemistry: How does the amino acid sequence of a protein determine its three-dimensional structure? And how does this structure relate to the protein’s function?

These questions are a matter of growing practical importance as the human genome is being delineated. Eisenberg helped develop a scoring method for assessing the compatibility of an amino acid sequence with a given three-dimensional structure. The application of this computational profile has already yielded accurate predictions for several enzyme structures.

In other work, Eisenberg and others elucidated the structure of the diphtheria toxin and suggested how this Y-shaped molecule binds to a bacteria, inserts itself into the cell membrane, then forms a component that translocates one of its domains into the cytoplasm. Other proteins studied in his lab include melittin, a membrane-associating protein useful in quantifying protein interactions; defensin, a protein of the innate immune system; glutamine synthetase, important in studies of salmonella and tuberculosis, and the cell growth factor, granulocyte colony-stimulating factor.

Eisenberg is a distinguished member of the Molecular Biology Institute at UCLA, where he directs the Biological Structure Group. He was the first elected president of the Protein Society, and is a member of the National Academy of Sciences and of the American Academy of Arts and Sciences.

A graduate of Harvard College, Eisenberg completed a doctorate in theoretical chemistry at Oxford University. He did postdoctoral research at Princeton University and at CalTech. He has received the Stein and Moore Award of the Protein Society and the Repligen Award of the American Chemical Society.

This year’s Neurath Lecture coincides with the 50th anniversary of the UW Department of Biochemistry and the 90th birthday of its founding chair.

“At its start, the department was on the leading edge as the field of biochemistry was describing proteins and determining their functions and controls,” said Dr. Kenneth Walsh, the present chair of biochemistry. These early investigations laid the groundwork for the Nobel Prize awarded 35 years later to the UW’s Dr. Edwin Krebs and Dr. Edmond Fischer.

With time, the department’s research broadened to include structural biochemistry of molecules at one extreme to developmental biology at the other. Along with several other UW departments, Biochemistry played an important role in the molecular biology revolution, which is changing medical science’s approach toward treating disease.

UW biochemists helped develop transgenic technology that allowed a gene from another species to be inserted into murine models, where its action could be studied. Others made major discoveries in blood coagulation, work that became fundamental to understanding clotting disorders and wound healing. Continuing research looks at the genetic controls of cell differentiation, the molecular basis of vision, and the role of cholesterol.

Walsh said that biochemistry is moving away from taking molecular systems apart and describing their individual components. More and more the field emphasizes how these components interact and how these interactions fit into the larger scheme of cellular biology.

“Scientists hope to learn the secrets of cellular systems in order to provide molecular repairs as needed,” Walsh said. He was circumspect about speculating where biochemistry will be the next few years: “The molecular world is changing rapidly. As scientists begin to define the future, it quickly becomes the past.” ¶

Leila Gray

“Protein-Protein Interactions”
Dr. David Eisenberg
Professor of Chemistry and Biochemistry
University of California - Los Angeles

2:30 p.m.
Friday, Oct. 29
Turner Lecture Hall: D-209 HSC