NBU BIF
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Research

Right from its establishment, the NBU Bioinformatics Facility has been concentrating on the research in various aspects of comparative genomics, molecular genetics, genomics and proteomics of nitrogen fixing bacteria and food pathogenic bacteria. Recently we have also diverted by research focus on Probiotics and Cynobacteria.

Thrust areas
Codon usage analysis, Comparative genomics, protein structure prediction, biological sequence analysis, phylogenetic study, molecular modeling and molecular dynamics are some of the major thrust areas of the centre. The Coordinator’s group is actively engaged in research in the field of Molecular genetics and molecular diversity of soil symbionts like Rhizobium and Frankia. Database development also features in our current research plans.

Motive
In recent years our understanding of biological nitrogen fixation and bacterial pathogenesis has been bolstered by a diverse array of scientific techniques. Large-scale genome projects have resulted in the availability of tremendous amount of biological data. This data includes information about genomes which in turn gives the idea about proteins, codon usage etc. The development of bioinformatics and statistical genetics, have resulted in the production of a number of tools, which are used to annotate the genome and obtain fruitful data from them. Bioinformatics has a great potential in studying the diversity of nitrogen fixing and food pathogenic bacteria in providing capacities to preserve, improve biotic resources and control diseases that threaten human existence. Our laboratory is well equipped with every modern facility required for molecular biology research and taking these things into consideration we started to venture into newer dimensions of research utilizing bioinformatics tools.

Organisms under consideration
For our study we took complete genome sequences of a number of nitrogen fixing bacteria coming from cyanobacteria, proteobacteria, green sulfur bacteria, gram positive actinobacteria, firmicutes and the archaea so as to get a comprehensive idea about nitrogen fixation at all levels, make comparative analysis and understand the mechanism of nitrogen fixation from the genomic point of view. Special thrust has been given on Frankia. Frankia usually makes symbiotic associations with woody dicot plants and unlike Rhizobium its host plants are diverse and mostly forest trees. They help establish and maintain forests and shrub-lands, particularly in occasions where climate change or human activities disrupt ecosystems. Therefore, Frankia is an important organism from the silvicultural point of view. Besides Frankia, Other actinobacteria like Streptomyces,Mycobacteria and their comparative genomics with Frankia, is another vital area which we are currently focusing on.
For the study of bacterial pathogenesis, we focused our attention on food pathogenic bacteria especially, Salmonella, Vibrio, Campylobacter, Helicobacter, and Xanthomonas. These bacteria are responsible for large scale diseases throughout the world and study of the molecular organization of their genomes will enlighten us about newer aspects of pathogenesis and in the long run will help us in designing more efficient methods to control the diseases caused by them. We are also considering the codon usage pattern of different probiotic bacteria like Lactobacillus, Bifidobacterium etc. Since, little work on codon usage analysis, molecular phylogenetics and molecular modelling had been done with the aforesaid bacteria we thought of working in these frontiers. It is very much essential to know that the 3-D structure of proteins, codon usage patterns and organization of the proteomes to understand the mechanism of its function.

Work done so far
We have done synonymous codon usage analysis of many diazotrophs such as Bradyrhizobium japonicumFrankia EuIK1, Frankia CcI3, Frankia EANIpec, Frankia ACNI14a,  Azotobacter vinelandii, methanogenic archaea, Xanthomonas, Chlorobium Salmonella etc. Moderate codon bias was reported in Bradyrhizobium and this was attributed to translational selection. Comparison of the synonymous codon usage of the whole genomes of three fully sequenced Frankia strains revealed significant insights into their lifestyle. As expected for a high G+C rich organism, codon usage was highly biased but differences were observed among the three strains. These results ontained in the analysis supported the hypothesis that CcI3 was becoming a symbiotic specialist and the other two were maintaining their capacity to exist as free-living soil dwellers. In Azotobacter vinelandii considerable amount of heterogeneity among the genes were observed. Unlike the ribosomal proteins which were governed by translational selection, those associated with nitrogen fixation were affected by mutational pressure. Highly expressed genes were affluent in GC rich codons. Highly expressed genes present in COG groups were identified and majority of them were associated with major metabolic functions. The presence of highly expressed genes associated with nitrogen fixation revealed the capability of the bacterium to survive in free-living state and fix nitrogen in a manner somewhat different from the conventional.
Codon usage patterns of methanogenic bacteria revealed low bias and expression levels. Homogeneity in codon usage patterns among the genes of the genomes suggested that they have not gone through purifying selection. Translational selection was strongly operational in selecting codon usage variation in the nitrogen fixing genes of the methanogens. Expression levels did not play a role in synonymous selection. Analysis of synonymous codon usage patterns in Xanthomonasgenomes revealed a high degree of conservation. The genes associated with pathogenesis were affected by mutational pressure and were predicted to have low expression levels. Most of the genes were moderate to highly bias. Highly expressed genes in the COG groups were identified and their possible functions were analyzed. Studies on analysis of codon bias in Chlorobium reflected their lifestyles and adaptation to extreme environments. Similar work on Salmonella genomes highlighted the influence of specific genes associated with pathogenicity acquired by horizontal gene transfer mechanisms.
Besides working on Codon usage analysis, we have worked on the in-silico analysis of several nitrogenase proteins.  We have developed molecular models of Nif H proteins from three Frankia strains and one strain of Bradyrhizobium using the protein homology modeling technique. Our models are quite reliable with their structural and biochemical properties. The models are of good quality and highlight the functioning of the Nif H proteins. The homology models of Frankia Nif H revealed the structure function relationship. The 3D structure of these proteins has been further utilized for structure based phylogenetic studies and identification of functional divergent amino acid residues. Currently molecular dynamics of these proteins are being worked upon.   We have also developed a method for nucleotide triplet based method for studying phylogenetic relationships. This method is called Condensed matrix method. Characterization of nitrogen fixation genes using condensed matrix method and construction of dendrogram with the leading eigen values has been done to determine evolutionary relationships among the nitrogen fixing organisms. We have reported the interplay of horizontal gene transfer, paralogous duplications and genome duplications as significant forces in the evolution of the nitrogen fixers. The re-examination of the evolution of nitrogen fixation using nif D, nif K and nif H genes based on condensed matrix method offer novel insights into their evolution. We have also utilized this condensed matrix method for the phylogenetic analysis of latest genomes of swine flu viruses. Phylogenetic analysis portrayed the role played by rearrangements in controlling their evolution.
We have worked on identification and role of genes carrying the rare TTA codon in Frankia. The TTA codon, one of the six available codons for the amino acid leucine, is the rarest codon among the high GC genomes of actinobacteria including Frankia. However Frankia strains have maximum number of genes bearing this rare codon amongst the Actinobacteria. We have looked at the functional role of these genes, their expression pattern with respect to their codon usage and their evolutionary significance. Finally we looked at the possible significance of TTA codon as the optimal codon in translational machinery. For this we have generated a reliable full atomic 3D model of the t-RNA recognizing this codon with the objective of looking closely to the codon-anticodon interaction.
Currently we are working on identification of signal peptide and secretory protein genes in 21 strains of Mycobacterium based on computational method. The Signal peptide detection algorithms have been utilized to fish out various secretory proteins. The expression patterns of genes coding secretory proteins were predicted by calculating the Codon Adaptation index (CAI). The prediction of cleavage sites reveals that the cleavage occurs in the first 50 amino acids of the sequences. The Codon usage and Correspondence analysis of the secretory genes were also carried out. Based on this information a database of secretory proteins genes of Mycobacterium is being currently developed.
We have also worked on the secretome of several actinomycetes like Frankia strains and related Actinomycetales like Corynebacterium, Mycobacterium, Nocardia and Streptomyces etc. We have utilized the Signal peptide detection algorithms to indentify the various secretory proteins system in these bacteria. The codon usage pattern of the signal peptide genes reflects that these genes are highly expressed and show high codon bias in most of the genomes. The genome based secretome analysis presented here together with proteomics studies may provide vital clues for better understanding of the secretory mechanism. Sec type of signal peptide was found to be the most common type of signal peptide found across actinomycetes. The rates of silent mutations to non-silent mutations have also been assessed in Frankia, of which several genomes have recently become available to detect evolutionary pressures. A comparative genome analysis of scretome of Frankia have been carried to investigate  the selective pressures shaping their evolution.
Recently, a database on mycobacterial secretomes has been developed-MycoSec. The database is a gateway to the predicted secretomes in all finished mycobacterial genomes available in public domain. All relevant information pertaining to secretomics in Mycobacteria have been incorporated in the database. Mycosec promises to be a useful repertoire providing plethora of information. The databse certainly promises to benefit researchers working in the field of mycobacterial pathogenesis and aiming to explore the biomedical complicacies of Mycobacteria from a secretome perspective. Other than these another database has also been developed on Bamboos of North Bengal. The database is called Bambooinfoline. This database provides enumeration of the different species of bamboos found in North Bengal, with special emphasis on taxonomy, edible properties, chemical constituents, morphological features along with tissue culture specifications, which in turn will benefit the scientific community.

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DATABASE
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genome Genome Projects
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