Sigma and the Tale of a new city

I recently joined the Computational & Functional Genomics department of the Centre for DNA Fingerprinting & Diagnostics, at Hyderabad, as a Doctoral candidate.

My Doctoral studies will focus on the molecular mechanisms of the sigma factors of Mycobacterial genomes. Sigma factors control initiation of gene expression, and act as the recognition domains of RNA polymerase enzymes for specifically recognizing DNA sequences. In effect, the presence (or absence) of sigma factors regulates which genes are expressed.

Individual genes are preceded by short tags, called promoters. These genetic beacons act as colour-coded post-its, read by the sigma factors. For example, lets assume the cell is exposed to excess heat. The cell ceases all activity, goes into red alert, and activates the heat stress sigma factor, the “in case of fire” secret dossier. This dossier contains the locations of all heat stress proteins (a sort of sleeper cell, if you will), which must be activated pronto. The sigma factor discloses the location of these genes to the transcriptional machinery, allowing them to be expressed.

The cell maintains an arsenal of different sigma factors, to be activated under specific conditions. For example, DNA damage, heat shock, osmotic shock, hypoxia, etc.

My Doctoral work will focus on the exact mechanism of sigma factors within Mycobacteria, the causative agents of TB and leprosy. Mycobacteria are extremely hardy bugs, and can survive under a multitude of conditions and extreme environments. They are also incredibly slow growing, which makes studying them very difficult. M.tb has 13 sigma factors, while the average gut bacteria has only 7. It is predicted that some Mycobacteria have as many as 26 different sigma factors. The implications of this are astounding.