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Scientists identify new strategy to fight deadly infection in cystic fibrosis
Date:1/23/2013

siRNA, to silence a specific gene and reduce the protein's activation. Amal plans to next test this protein-lowering technique in mice that are models for cystic fibrosis. Designing a similar strategy in humans would require many years of additional study, she noted.

The study is published in the current issue of the Journal of Biological Chemistry.

The cells that can use autophagy to clear infection are macrophages, which are first responders in the immune system that consume offending pathogens.

In previous work, Amer and former Ohio State doctoral student Basant Abdulrahman showed that in macrophages isolated from both mice and humans that carried the most common CF mutation, the bacterium would invade the macrophage and thrive instead of being digested and cleared away as it was in cells without the mutation.

The research group showed that rapamycin, an existing drug known to stimulate autophagy, helped control B. cenocepacia infection in mice that serve as a model for cystic fibrosis.

"Rapamycin worked well as a proof of concept, but it has so many side effects that it's hard to imagine giving it to small children with CF for an extended period of time. That's why we looked for another method," said Amal, also an investigator in Ohio State's Center for Microbial Interface Biology (CMIB).

For this study, the researchers conducted experiments in macrophage cells derived from mice carrying the CF mutation and compared them to macrophages from normal, healthy mice.

The researchers observed in macrophages with the mutation that when p62 is elevated, other cell components clump together, causing disruption to the autophagy process.

"p62 is a sticky protein, so high levels of it lead to the formation of aggregates. Once we get rid of that sticky protein the glue these protein aggregates will be able to go where they are supposed to go and allow the autophagy process to work properly," A
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Contact: Amal Amer
amal.amer@osumc.edu
614-247-1566
Ohio State University
Source:Eurekalert

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