We are interested in understanding the molecular mechanisms of DNA replication and packaging in double-stranded DNA viruses. We employ bioinformatics, molecular genetics, biochemical and structural biology approaches.
Genome encapsidation into preformed empty capsid shell is a common phenomenon in many bacteriophages (eg., T4 and lambda), eukaryotic viruses (eg., herpes viruses) and nucleocytoplasmic large DNA viruses (NCLDVs) such as mimivirus and marseillevirus. Two major types of DNA packaging systems are found in viruses; a terminase-portal mediated DNA packaging system that is operative in many tailed bacteriophages and a HerA/FtsK-type ATPases mediated packaging in many viruses with inner lipid membranes. While the terminase-portal packaging systems have been studied in many viruses like T4, lambda, SPP1 and HCMV for over two decades, FtsK-ATPase mediated packaging mechanisms have not been addressed in any system so far. We seek to employ amoeba-infecting viruses as models systems.
Mimivirus and other NCLDVs encode for a number proteins involved in DNA precursor biosynthesis, replication and repair. Some of these are predicted to be of ancient lineage with probable pre-eukaryotic origins and are thought to be pivotal in major evolutionary transitions. Understanding molecular mechanisms underlying the function of some of these important enzymes will help us decipher how large, complex double stranded DNA viruses are assembled. It will also help us understand the origins and evolution of large DNA viruses.