Computational and functional genomics of bacterial gene regulation...

Bacteria, besides being agents of a variety of infectious diseases, are the most predominant form of free-living life known on Earth. Some bacteria live in stable environments, such as in a symbiotic relationship with a host; others can live across multiple habitats each presenting its own set of nutrients and adversaries. This leads to two key points which are of interest to us:

(a) Any given bacterium should code for only those genes that would allow it to make optimal use of the conditions prevailing in its set of habitats.

(b) Regulation is critical especially to organisms that traverse multiple types of habitats, to ensure that only those genes required at any given time point are expressed.

The primary focus of our research is to investigate bacterial regulatory systems from the stand-point of both their occurrence in diverse bacterial genomes and their role in achieving global and function-specific gene expression control in model bacteria such as Escherichia coli.

We tackle our research questions using genome-scale techniques. Genomics complements the detailed findings of reductionist molecular biology and biochemistry by describing general principles and identifying exceptions. The large-scale nature and the gaining popularity of genomic studies together generate a flood of biological data, the interpretation of which requires computational tools and expertise. Therefore, our research includes active experimental and computational components.

Our specific research questions encompass the following (at present; may be gibberish to the uninitiated):

1) How do bacteria utilise the available carbon source?

- Decoding the paradoxical effects of a cyclic adenylate E.coli mutant.
- Role of cAMP in utilisation of various carbon sources.

2) The rate of divergence of transcriptional regulatory circuits in Bacteria.

- Intra-specific diversity of transcription factors and their targets in E coli inhabiting diverse niches.

3) How does replicative structure of the bacterial chromosome impact genome-wide gene expression patterns in Escherichia coli?

- What are the evolutionary strategies accessed by bacteria to compensate perturbations in the replicative structure of the chromosome?

4) Effects of the origin of replication on global expression and chromosomal structure in Escherichia coli.

- Does the position of origin of replication have an effect in global expression and chromosome structure?
- Is replication initiation dependent upon local chromosomal context?

5) Probing the genetic and phenotypic change of E.coli in complex, naturally relevant stress over time

- Genetic and phenotypic characterisation of E.coli in prolonged stationary phase : looking at the survival effects of RpoC A494V mutation

6) Understanding the pattern of distribution and conservation of different repair systems in bacteria.

- Comparative genomics of Non-homologous end joining double strand break repair in bacteria to understand it's pattern of distribution.
- Is the repertoire of repair machinery which a given bacterium possesses dependent on it's environmental niche or the kind of stresses it faces?

7) Genome scale study to understand the diversity, antimicrobial resistance and virulence in the Indian varieties of Klebsiella pneumoniae , a major pathogen categorised in the Red list by WHO.

8) Computational study to understand the constraints on organisation and sequence of DNA repeats in prokaryotic genome.