Prediction and characterization of Mycobacterium small RNAs
Description: Prediction and characterization of Mycobacterium small RNAs
Introduction
Mycobacterium is a genus of Actinobacteria that include some species of great medical and economic importance, such as Mycobacterium tuberculosis, M. leprae, M. avium, and M. bovis, that are responsible for severe diseases in human and animals. An initial characterization of certain gene clusters on the genomes of Mycobacteria identified several regions to be highly conserved.
Proteins were long regarded as key regulators of the control of bacterial gene expression, however, the recent discoveries have shown that small RNAs (sRNAs) also play central role in regulating the functions of diverse genes. The search for new sRNAs have traditionally focused on Salmonella and E. coli, however, according to our knowledge much less attention has been diverted to other medically important pathogens including Mycobacterium. The only human pathogen that has received any attention is the Pseudomonas aeruginosa. In 2006 an elegant study by Livny J et al. (1) has identified 17 sRNAs in P. serugionosa genome and predicted several sRNA-encoding genes in 10 diverse pathogens.
Objectives
1. Search for sRNAs in Mycobacterium tuberculosis and M. smegmatis genomes
The main objective of this study is to: in silico prediction of sRNA genes in pathogenic M. tuberculosis and a non-pathogenic M. smegmatis genomes. A variety of approaches (reviewed by Vogel and Shama, 2005) for the genome-wide identification of chromosomally encoded sRNAs have been developed. Based on these knowledge we will take biocomputational approach to identify mycobacteria-specific sRNAs.
2. Prediction of sRNA targets
In silico prediction of sRNA targets has successfully been applied in prokaryotes. These predictions are made on the basis of sequence complementarity between sRNA and its target mRNA. Using similar approach the target genes will be predicted. Biocomputationally identified potential targets will be validated by the wet lab experiments. For this the sRNA will be overxpressed using suitable vector and degradation of its targeted mRNA transcripts will be validated using microarray approach. Furthermore, mechanisms of regulation of target genes by sRNAs will be studied in detail.
3. Functional characterization of the identified targets
Interesting target genes related to bacterial virulence, intracellular survival and induction of innate immune responses will be functionally characterized.
Key words: bioinformatics, systems biology, sRNA, microbiology
Latest application date: 2009-12-21
Financing: Erasmus Mundus External Cooperation Window
Type of Position: scholarship
Duration of the Project : 4 years
Research group: Department of Microbial and Molecular Systems (M#S)
Remarks: This project would fit in Lot 13, collaboration with India and requires a collaborative effort between KUL (bioinformatics analysis) and wet lab (group of A. sonawane). The work would be partim in the KUL partim in India.
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