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Study finds new vulnerability in malaria parasite
Date:11/27/2013

imidazopyrazines by evolving parasite cell lines that were resistant against the drugs and then analyzing the parasites' genomes for the changes responsible for conferring resistance. Those genetic changes pointed to the gene that encodes PI4K.

The CUMC team, led by David Fidock, PhD, professor of microbiology & immunology and medical sciences (in medicine), used novel genetic tools to confirm that PI4K was being directly targeted by the imidazopyrazines.

Then, using cellular imaging, the CUMC team found that imidazopyrazines interfere with the function of PI4K on the parasite Golgi (the organelle that packages proteins for delivery to other cellular destinations). "We think that disrupting the function of PI4K at the Golgi stops the parasite from making new membranes around its daughter cells, thereby preventing the organism from reproducing," said Dr. Lee.

Because PI4K is also found in humans, Dr. Winzeler said, the next challenge is to develop a drug that retains selectivity between the parasite and human versions of the enzyme. "As we now know the identity of this protein and hope to soon solve its structure, this task should be much easier," she said.


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Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert  

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