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Newsletter:  May 2003/ Issue 4
Antibody Library Enables Rapid Pathogen Detection

The rapid detection of pathogens has consistently been at the top of experts’ lists of the capabilities needed to protect public health and the environment. Since September 11, this need has only grown more pressing. Being able to quickly and precisely determine the presence and nature of biological contaminants protects both soldiers on the battlefield and civilians in the event of a terrorist attack.

One promising approach to pathogen detection is the use of antibodies, proteins that white blood cells produce as part of the human immune system. Antibodies bind to specific proteins on bacterial pathogens, signaling other cells to either kill or remove the bacteria. Antibodies can be used in detection devices to locate proteins of biological warfare agents. And, in industrial applications, antibodies are effective tools for recognizing specific molecules.

Now scientists at the Pacific Northwest National Laboratory (PNNL), working with a colleague at the Massachusetts Institute of Technology (MIT), have developed processes to enable the rapid identification of new antibodies. Michael Feldhaus and Robert Siegel of PNNL’s Fundamental Science Directorate have built an array (“library”) of one billion human antibodies and expressed them on the surface of yeast cells using an approach designed by collaborator Dane Wittrup of MIT.

By incorporating Wittrup’s yeast display method, Feldhaus and Siegel can readily modify how an antibody binds to proteins. Being able to increase how tightly a protein and antibody bind together could enhance the effectiveness of antibodies in detecting pathogens and disease. This innovative approach could replace the need to produce antibodies within animals, particularly mice, and opens up new possibilities for rapidly designing medical treatments more acceptable to the human immune system. In medical treatments, antibodies are injected into the body to seek out specific proteins on cancerous cells, for example, and target treatment to those cells. So, development of the antibody library may significantly advance the use of antibodies in biological warfare detection devices, in sensors, and in medical diagnostic tools and therapeutic agents.

“Our antibody library offers many advantages over traditional approaches,” said Michael Feldhaus. “We expect it will be a more effective tool for scientists. Regulated expression of these antibodies allows the library to be expanded while maintaining its diversity. Furthermore, our unique identification process means we can screen for antibodies in days rather than the months it may take using other approaches. Our approach, through the sample preparation and cleanup it provides, gives detection methods such as PCR incredible detection sensitivity.”

The National Science Foundation, the Hereditary Disease Foundation and PNNL’s Biomolecular Systems Initiative have provided funding for Feldhaus and Siegel’s research. The Department of Energy is supporting the scientists’ application of the antibody library to the detection of biological warfare agents.