Our Research

Giant Viruses: Bigger, stranger, and smarter

The discovery of giant viruses, starting with Mimivirus in 2003, the biggest virus at that time, has reshaped our understanding of viruses. Remarkable for their large particle size and complex genomes, these viruses often exceed the dimensions of many bacteria and encode functions previously thought exclusive to cellular organisms. Research on giant viruses in the last 15 years has established their ubiquity. A variety of new giant viruses have been isolated as well as discovered in the metagenomic studies. We are interested in the isolation of novel giant viruses, their comparative genomics, and the biochemistry of DNA processing enzymes of these viruses. We also dabble in a few related areas!

“In a flash I had the solution… a virus parasitic on bacteria.” — Félix d’Hérelle, 1917

Bacteriophages, once recognized as the natural predators of bacteria, have become powerful model systems in molecular biology. They played a pivotal role in the early development of molecular genetics and continue to drive insights into host-pathogen coevolution and bacterial resistance mechanisms.

In our lab, we isolate diverse phages and apply bioinformatics, comparative genomics, and structural biology to characterize their diversity, architecture, and function. We aim to uncover the mechanisms underlying the phage replication cycle, and decode how phages adapt to and overcome host defenses.

Mimivirus: A prototype large DNA virus

Genome Segregation, Packaging, and Condensation

Genome packaging is a critical and tightly regulated step in the viral life cycle, involving intricate molecular events. Some viruses employ ATP-dependent motors to actively translocate their genetic material into preformed capsids, while others assemble their capsids around the genome in an energy-independent manner. Our lab focuses on deciphering the mechanistic basis of energy-dependent genome packaging, integrating biochemical, structural, and comparative genomic approaches. We are currently investigating the terminase–portal packaging system in bacteriophage N4 and related tailed phages and the FtsK/HerA-superfamily ATPase–driven packaging mechanism found in nucleocytoplasmic large DNA viruses (NCLDVs), using vaccinia virus and amoeba-infecting giant viruses as model systems.

Viral Genome Replication and Repair

Mimivirus enters host cells via phagocytosis and replicates exclusively within cytoplasmic viral factories, where it has limited access to host DNA replication machinery. To overcome this, it encodes its own suite of replication enzymes, including a family B DNA polymerase, multiple primases, helicases, and other key components of a self-sufficient replication system. However, the viral factories impose oxidative stress on mimiviral DNA, making genome integrity a major challenge. Genomic and proteomic analysis revealed the presence of DNA repair polymerases, mismatch repair proteins, and several enzymes involved in the base excision repair (BER) pathway, suggesting a robust, virus-encoded repair toolkit.

Our lab focuses on unraveling the mechanisms of mimiviral DNA replication and repair, using a combination of biochemical assays and structural biology to dissect the molecular players involved.

Biochemical activities of the mimiviral PrimPol

Genomes of the giant viruses isolated from India

Metagenomics

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