I obtained my M.Sc. and Ph.D. in Advanced Cytogenetics from the University of Calcutta, India. I received the Young Scientist Award in 1991 and also the Nehru Centenary British Fellowship to continue my doctoral work in the UK. After my Ph.D. I joined as a postdoctoral Research Fellow in the Department of Biology at Harvard University, and later moved to the University of Missouri in Columbia. I got an independent position in Missouri after one year.

“Our study demonstrated that RNA interference machinery plays a role in heterochromatin silencing in higher eukaryotes, such as Drosophila, as reported earlier in S. pombe.”

I joined CCMB, India, as a Senior Scientist in 2002 and was promoted as a Group Leader within a year. I have been recently selected as an International Fellow of the Wellcome Trust organization from the UK and a top Young Investigator from the Human Frontier Science Program. I have also been selected as a Fellow of UNESCO and the Australian Expert Group of Industrial Study (AEGIS) and a Fellow of National Academy of Science (FNASc) here in India.

Identification and characterization of several transacting dose-dependent regulators targeting white eye color genes in flies was the main focus of my Ph.D. work. I analyzed their specific roles in sex determination and dosage compensation, a natural phenomenon for epigenetic genome control. We identified that the transacting dosage effect, which is the basis for aneuploid syndrome, has a tremendous impact on hyperactivation of male X chromosome. The in-depth studies showed that the Male Specific Lethal (MSL) proteins, which are thought to control dosage compensation by painting the male X chromosome, have negligible effect on hyperactivation of X-linked genes. In reality, they modulate the transacting inverse dosage effects, which has a global impact on the genome regulation and becomes proactive by the loss of one X chromosome in the male.

During my stay at the University of Missouri, we accidentally identified a phenomenon—Co-suppression, the strategy by which plants often silence the expression of multiple transgenes or foreign DNA or transposon activity when they are inserted in different chromosomal locations. Our experiment in flies using w-Adh hybrid transgenes appears to be a first case of co-suppression in animal species. Later, we extended this phenomenon on other hybrid genes to determine its generality.

We also found a case in which w promoter-Adh reduced the expression of reciprocal constructs Adh-w intensively using endogenous Adh as a mediator. We referred to this strategy as "non-homologous co-suppression." An experiment on multiple Adh full-length transgenes revealed that silencing occurs at post-transcriptional level by a sequence-specific RNA degradation process that shares the hallmarks of RNA interference (RNAi), a powerful tool for functional genomics. In the last three years, milestone contributions of RNAi machinery regarding heterochromatin silencing, chromatin dynamics, and nuclear organization have been elucidated from our works.

  Your 2004 Science paper, "Heterochromatic silencing and the HP1 localization in Drosophila are dependent on the RNAi machinery," has been singled out as a highly cited recent paper on gene silencing. Would you please sum up this paper and its significance for the field?