Researchers from the University of Pittsburgh and Stanford University have discovered that a supposedly inactive protein actually plays a crucial role in the ability of one the world’s most prolific pathogens to cause disease, findings that suggest the possible role of similar proteins in other diseases. The team reported online on March 21, 2011, in PNAS that Toxoplasma gondii—the parasitic protozoan responsible for toxoplasmosis—attacks healthy cells by first injecting them with pseudokinases, which are enzymes that have abandoned their original function of transferring phosphates. When the researchers engineered strains of T. gondii without a particular pseudokinase gene cluster called ROP5, the pathogen was subsequently unable to cause disease in mice—a notable loss of potency in an organism that can infect nearly any warm-blooded animal. These results are among the first to implicate pseudokinases as indispensible actors in pathogen-based disease, said senior author Dr. Jon Boyle, a professor in the Department of Biological Sciences in Pitt’s School of Arts and Sciences. Dr. Boyle co-authored the paper with Dr. John Boothroyd, a professor of microbiology and immunology in the Stanford School of Medicine. Drs. Boyle and Boothroyd worked with Dr. Michael Reese, a postdoctoral researcher in Dr. Boothroyd’s lab, as well as Drs. Gusti Zeiner and Jeroen Saeij, former postdoctoral researchers under Dr. Boothroyd. The Pitt-Stanford project suggests that the significance of these “functionless” enzymes to T. gondii could apply to pseudokinases in other pathogens, Dr. Boyle said, including the parasite’s close relative Plasmodium, which causes malaria. “Our work shows that just because these proteins have lost their original function does not mean they don’t do anything,” Dr. Boyle said. “T.
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