Graduate of Department of Biotechnology and Bioinformatics

AG 1, AG 2, AG 3, AG 4, AG 5, SWS, RG1, MMCI   Info

Public Audience

English

120 Minutes

Saarbrücken

Fatty acid degradation (fad) pathway is one of the alternate metabolic pathways which enables the survival of M.tuberculosis during phases of dormancy. Fad pathway is suggested to be controlled by the expression of fadR gene, which elevates the significance of fadR gene in regulation of fad pathway. Apart from this there are multiple genes within M.tuberculosis genome annotated with same function but loosely associated with functional pathways. Based on such unexplored aspects of M.tuberculosis physiology with respect to fad pathway, below goals were set forth for this study:
1.  Identifying significance of FadR under growth arrest(dormancy) conditions by   determining its corresponding regulon. This study could help us establish the status of fadR   as a probable global regulator.
2.  Establishing any functional significance for the multiple genes attributed to same   function in M.tuberculosis genome specifically fad/fadR genes.
3. Our primary agenda in this study revolves around finding some overlap in genes   between fadR regulon and crp regulon (cAMP receptor protein and its gene is a known   global regulator in many prokaryotes) in order to determine the nature of such genes and   their corresponding pathways dependent upon these two   regulators.
Each of the queries put forth above deem significance in identification and categorisation of the genes enabling transition into dormancy and sustenance of the infection. It can help us better our understanding of the mycobacterial physiology and design new strategies to overcome this pathogen. The merit of finding the overlapping genes from the fadR and crp regulon is that the common genes are probably the most crucial genes(target genes) in sustenance of Mycobacterium.
Expression data analysis techniques and gene regulatory networks were the two key computational areas I explored in this study. Summarising the study I reached the following conclusions:
1.  Rv0494 and Rv0586 emerged as the only two fadR genes which showed a   substantial expression change during starvation and hypoxia signifying the   greater part played by these genes under growth arrest.
2. FadR protein is more skewed towards repressing fadD gene than other genes in fad   pathway like fadE, echA or itself. FadR protein binds to fad genes in a   decreasing order of affinity from fadD to fadR thereby regulating fad pathway.
3.  Common regulatory network of fadR and crp suggests that they regulate genes   responsible for amino acid biosynthesis and redox reaction. The fadR regulon has 7 genes   predominantly from intermediary metabolism and cell processes.
4.   Our study also provides a credible computational evidence that fadR translational start site   has been currently misrepresented in M.tuberculosis. Phylogenetic and SD   sequence analysis of the nucleotide sequence concurs the same.
Multiple expression data profiles were employed to study the behaviour of fad genes under various growth arrest conditions and their corresponding regulons/networks were integrated with crp gene network profile to get a comprehensive overview of the fadR- crp regulon. Subsequently, fadR regulon was obtained using a three fold method (expression profiles, sequence based analysis and chip-sequencing data).

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