Research

The concept of giant viruses is relatively new. The discovery of mimivirus in 2003, the biggest virus at the time, completely changed the way we look at viruses. In terms of both particle size and genome size, mimivirus is bigger than several bacteria. Research on giant viruses in the last 15 years have established their ubiquity. A variety of new giant viruses have been isolated as well as discovered in the metagenomes. We are interested in isolation of novel giant viruses, their comparative genomics and biochemistry of DNA processing enzymes of these viruses. We also dabble in a few related areas!

Genome encapsidation is an essential process in the virus lifecycle. Some viruses use ATP-dependent motors to package their genetic material into a preformed capsid, while in others, the capsid is assembled around their genome in an energy-independent manner. ATP-dependent packaging occurs either using a terminase-portal system, or is mediated by a packaging ATPase of FtsK/HerA superfamily. The former is generally present in tailed phages whereas, the latter is found in nucleocytoplasmic large DNA viruses (NCLDVs), inner lipid membrane containing phages and filamentous phages. Our lab is interested in understanding the mechanistic details of energy-dependent virus assembly and genome packaging mechanisms. We are currently working on terminase-portal system of bacteriophage N4 and FtsK-type ATPase driven assembly of NCLDVs, using vaccinia virus as well as amoeba-infecting giant viruses as model systems.

Mimivirus replication takes place exclusively in the cytoplasmic viral factories where they have limited access to DNA replication enzymes of the host. In addition to the family B polymerase, mimivirus also encodes several primases, helicases and other essential components of the replication machinery. Also, owing to its phagosomal mode of entry, mimiviral genomic DNA is susceptible to oxidative damage. Genomics studies of mimivirus identified the presence of DNA repair polymerases, mismatch repair enzymes and several enzymes involved in the base excision repair pathway. Our lab aims to decipher the mechanism of mimiviral replication and repair using biochemical and structural biology based approaches.

Metagenomics is a culture-independent, next-generation sequencing-based approach of identifying and studying microbial population structure of an environment. While large chunk of bacterial and viral population are yet to be discovered and are considered dark matter, metagenomics has been able identify novel species from different environments. Straddled between cellular life forms and simpler viruses, Giant Viruses(GV) and their ecological niche is a theme of intense research. The discovery of GVs from diverse geographies is critical for deciphering their evolutionary history. We use metagenomics to (1) identify and characterize giant viruses and bacteriophages from different environments and (2) for understanding the resistance potential of the environment in the context of the virome.