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Milestone in Fight Against Deadly Diseases

Scientists work together to map and solve 500 protein structures

December 7, 2010 | by Erin Spain
CHICAGO --- Researchers at Northwestern University Feinberg School of Medicine are part of a nationwide project that has reached a major milestone in the effort to wipe out some of the most lethal diseases on the planet.

Since 2007, researchers have experimentally mapped out 500 3-D protein structures from bacterial and protozoan pathogens. Scientists can use information from these structures to design drugs, vaccines and diagnostics to combat deadly infectious diseases.

Some of the structures solved so far by Feinberg’s Center for Structural Genomics of Infectious Diseases include proteins from disease-causing organisms such as: Bacillus anthracis (anthrax), Salmonella enterica (salmonellosis food poisoning), Vibrio cholerae (cholera), Yersinia pestis (plague) and Staphylococcus aureus (staph infections).

The Feinberg center, along with a similar center at the Seattle BioMed Research Institute, is on track to ultimately identify nearly 1,000 structures by the end of 2012. The centers are funded by a five-year, $31 million contract from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

“In addition to the aim of providing a starting point for structure-based drug discovery, we can also use this research as a way to learn more about these pathogens and how they cause diseases, how they get around the immune system, how we defend ourselves against them and how they interact with us or their host,” said Wayne Anderson, professor of molecular pharmacology and biological chemistry at Feinberg and principal investigator of the project.

Recently, Anderson and his team determined the structure of a crucial enzyme in the shikimate pathway of Clostridium difficile, which is the most serious cause of antibiotic-associated diarrhea in humans and can lead to pseudomembranous colitis, a severe infection of the colon often resulting from eradication of the normal gut flora by antibiotics. The shikimate pathway is essential for plants and bacteria like C. difficile but is not present in animals, making this enzyme an attractive antibiotic target.

Portraits of these protein structures and others including the plague, cholera, rabies and H1N1 can been seen through the NIH-supported Protein Data Bank and can be seen here.

Feinberg's Center for Structural Genomics of Infectious Diseases is a consortium which includes researchers from the University of Chicago, the J. Craig Venter Institute (Rockville, Md.), University College London, the University of Toronto, the University of Virginia (Charlottesville, Va.), the University of Texas Southwestern Medical Center at Dallas and the Washington University School of Medicine (St. Louis, Mo.), in addition to Northwestern University. Click here for details.

Members of the scientific community interested in nominating protein targets for structural determination can complete a request form on the CSGID website. This service is limited to pathogens of Category A, B, and C of the NIAID priority list and is offered free of charge to the scientific community.

Topics: Research