Scientist's Research Opens Door to Treatment of Parasite Disease

ALBANY, NY (June 3, 2009) - Unusual features in a molecular machine crucial to the life cycle of a disease-causing parasite have been identified by a State Health Department researcher, opening a possible avenue for development of a novel drug to interrupt the process and diminish disease caused by the parasite.

Leishmania parasites, which are transmitted by the bite of sand flies, cause skin sores and more serious complications affecting the liver and spleen. The disease leishmaniasis is found in parts of the tropics, subtropics, and southern Europe. Leishmaniasis has been a growing concern during the deployment of U.S. troops to Iraq and Afghanistan, where the parasite and its sand fly vector are common. Nearly 1,300 cases have been identified in troops.

The findings by research scientist Rajendra Agrawal, Ph.D., who studies the cell's protein factory, called the ribosome, were published this week in the online early edition of the Proceedings of the National Academy of Sciences. The paper, titled "Structure of a Mitochondrial Ribosome with Minimal RNA," will be highlighted in the "In This Issue" section of the journal's June 16 print issue. Dr. Agrawal's work continues the distinguished record of the State Health Department's Wadsworth Center laboratories in illuminating ribosomal structure and function.

"New Yorkers are fortunate to have world-class biomedical researchers at the State Health Department's Wadsworth laboratories who are moving forward the field of molecular medicine," said State Health Commissioner Richard F. Daines, M.D. "Studying the biological machinery of life promises to improve health in the long term."

All organisms – from plants to parasites to people – rely on ribosomes to translate their genetic information into protein building blocks that support and sustain life. Composed of proteins and nucleic acids, ribosomes undertake this task throughout the cellular environment, including the specific cellular compartment known as the mitochondrion, the cell's power plant.

Using cryo-electron microscopy and sophisticated computational analysis, Dr. Agrawal and his team created a three-dimensional map of the Leishmania tarentolae mitochondrial ribosome (Lmr). They found that the Lmr differed in several ways from other ribosomes, including their mammalian mitochondrial counterparts. The different features of the Lmr, when characterized in greater detail through further studies, may provide targets for the development of drugs that would stop the parasite's protein synthesis, and therefore replication, while safeguarding the human host's ribosomes that lack these unique features.

Dr. Agrawal's co-authors are Dr. Manjuli Sharma and Timothy Booth of the State Health Department's Wadsworth Laboratories, and Dr. Larry Simpson and Dr. Dmitri Maslov of the University of California at Los Angeles and the University of California at Riverside, respectively. His research is supported by the National Institutes of Health. Dr. Agrawal is also an associate professor in the Department of Biomedical Sciences, School of Public Health of the University at Albany.