Argonne wins $5 million NIH grant to study membrane proteins for drug development

ARGONNE, Ill. (December 19, 2005) – Biologists at the U.S. Department of Energy's Argonne National Laboratory have been awarded a $5 million, five-year research grant from the National Institute of Health's National Institute of General Medical Sciences (NIH/NIGMS) to study membrane proteins, important for pharmaceutical development.

"Membrane proteins are the most challenging – but arguably the most important – proteins for structural biologists to tackle," said Peter Preusch, the program director at the National Institute of General Medical Sciences. "By lowering the barriers to solving their structures, these projects could lead to new scientific and medical insights that hinge on understanding membrane proteins."

One-third of human proteins are membrane proteins. Vital to health, they control the flow of information and materials between cells and mediate critical activities like nerve impulses and hormone action. Membrane proteins represent more than 60 percent of all drug targets, so understanding these structures could provide valuable contributions to the discovery and improvement of pharmaceuticals.

Membrane proteins are found naturally in cells at very low levels and, unlike the thousands of biomolecules whose three-dimensional structures have been determined, they are not water soluble. This makes membrane proteins difficult to study. Traditional protein crystallography techniques, used to determine thousands of structures, begin with dissolving the protein in water.

To determine a membrane protein's structure, the first step is to remove it from the lipid bi-layer where it resides, but previous attempts have failed to produce stable proteins for study. "With this grant," explained principal investigator and Argonne biophysicist Philip Laible, "we will develop specialized molecules, or reagents, that keep membrane proteins stable for crystallization."

Researchers will be focusing on three types of reagents:

• Designer detergents that remove the membrane protein from the lipid bi-layer where it resides
• Antibodies to stabilize the membrane protein, and
• Molecules that mimic the lipid bi-layer, or membrane.

A multidisciplinary team including researchers from Argonne, the University of Wisconsin and deCODE biostructures, Inc. of Bainbridge, Wash., will apply complementary expertise in biochemistry, synthetic chemistry, immunology and biophysics under the NIH grant.

The research has grown out of discoveries Laible and Argonne colleague Deborah Hanson, both of Argonne's Biosciences Division, found as part of an earlier NIH/NIGMS grant. The two developed and patented a technique to produce large quantities of membrane proteins for structural studies. "That technique will be used to generate membrane proteins samples we will use to test our reagents," said Laible.

This research is a part of the NIH Roadmap that is a series of strategic initiatives fueling the movement of research discoveries from the bench to the bedside.

The National Institutes of Health is the nation's medical research agency and includes 27 institutes and centers. It is a component of the U.S. Department of Health and Human Services, and is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and investigates the causes, treatments and cures for both common and rare diseases.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America 's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.

For more information, please contact Steve McGregor (630/252-5580 or media@anl.gov) at Argonne.