Study of Signal Transduction and Bacterial Pathogenesis in Host Cells Treated with Secretory Proteins Derived from Mycobacterium tuberculosis

  • Chan, Err-Cheng (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

The objective of this research is to investigate the cause of lung diseases by secreted proteins from Mycobacterium tuberculosis. Previously, we have successfully cloned and expressed the clone of ESAT-6/CFP-10 complex (CFES), combining cfp-10 with esat-6, and utilized a cDNA array technology to analyse altered gene expressions of host cells causing by secreting ESAT-6/CFP-10 in the infection process of Mycobacterium tuberculosis. By utilizing bioinformatics tools, it have predicted the important biological hotpots and shown the interaction of these genes. We found out the influence of CFES on the gene expression of human lung cells involved cell proliferation, cell motility, cell survival and cell apoptosis. And according to our preliminary results, it had verified CFES will cause chromosome condensation and induce apoptosis. This proposal hypothesize that CFES induce an apoptosis-related signal transduction enhanced the pathogenesis of M. tuberculosis. To prove this hypothesis, we will investigate the influence of CFES on the signal transduction predicted by cDNA microarray. The strategy combines the use of quantitative PCR, western blot and immunoprecipitation methods to identify the gene expression, protein expression and their involved signal transduction pathways. Once the signaling pathways have been identified, we will block these pathways by using certain kinase inhibitors or siRNA knockdown for the key proteins to observe if these interventions protect cells from CFES-induced apoptosis. Furthermore, we will also observe the relationship between immunogenecity and pathogenesis by treating WI-38 cells and THP1 cells with CFES. The results of this project will help us understand the mechanism by which M. tuberculosis causes the pathogenesis.

Project IDs

Project ID:PC9709-0938
External Project ID:NSC97-2320-B182-014-MY3
StatusFinished
Effective start/end date01/08/0831/07/09

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.