Title

Authors

Jerry Mobley Wright^1,*, Elisabeth Joseloff², Yuri Nikolsky³, Tatiana Serebriyskaya³, Diana Wetmore⁴

Affiliation

¹Department of Physiology, Johns Hopkins Medical Institutions, 725 N.Wolfe St. Baltimore, MD 21205; ²Cystic Fibrosis Foundation Therapeutics, Inc. Bethesda, MD;³GeneGo, Encinitas, CA; ⁴Emerald Biostructure, Bainbridge Island, WA 

Email

jwright@jhmi.edu; * Corresponding author

Article Type

Hypothesis

Date

Received September 01, 2010; Accepted October 10, 2010; Published November 27, 2010

Abstract

One unresolved issue in Cystic Fibrosis research is how functional loss of CFTR, a protein involved in chloride transport, results in chronic lung inflammation. Large scale experiments investigating protein or gene expression changes due to altered trafficking of the most common disease causing CFTR mutation (?F508) have produced long lists of changes with no apparent connection to inflammation. Likewise, experiments documenting the effects of inflammation in bronchial epithelial cell lines have yielded no insights into CFTR trafficking. We used MetaMiner CF to combine and analyze results of several CFTR trafficking and epithelial response to infection studies which were on different platforms using different methodologies and had different objectives. The program searches a manually curated database for published experiments linking proteins or genes and displays the interactions in a more easily understood graphic format. Numerous connections were established between genes documented to correct ?F508 trafficking and a list of genes differentially expressed in bronchial epithelial cells after exposure to bacteria or virus. Of 34 genes documented to correct ?F508 trafficking, 9 were directly linked by positive expression activation mechanisms to the immune inflammatory response. Looking at interactions among the results as a whole and in detail, it is apparent that an inflammatory response produces numerous changes which favor correct trafficking of ?F508. One can take a view of the inflammatory process as potentially a corrective mechanism for dysfunctional ?F508 trafficking. This opens up a new research direction and provides new targets in the search for disease treatments.

Keywords

Agents, Blast, Coalition, Grids, Virtual Machines and Virtualization.

Citation

Wright et al. Bioinformation 5(6): 228-233 (2010)

Edited by

Venkatarajan S Mathura

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.