Desiraze Narasimha Rao received BSc (1975) from University of Delhi, MSc (Biochemistry) (1977) from GB Pant University of Agriculture and Technology and DSc (Biochemistry) (1982) from Indian Institute of Science (IISc), Bangalore. He was Assistant Professor (1989-95), Associate Professor (1995-2001) and Professor, Department of Biochemistry (2001), and Chairman, Division of Biological Sciences, (2005- ), all at IISc. He was also Fogarty Visiting Fellow, National Institutes of Health, USA (1983-85), Postdoctoral Fellow, Biozentrum, University of Basel, Switzerland (1986-88) and Postdoctoral Research Associate, Department of Biochemistry, University of Cambridge, UK (1988-89).
Academic & Research Achievements: Rao's researches aimed at understanding how restriction-modification enzymes achieve their specificity and have chosen Type III restriction-modification (R-M) enzymes. He has shown that sequestration of a Type III restriction enzyme by intact recognition site on cleaved DNA and lack of such a phenomenon in case of type II enzymes, could be one reason as to why the later class of enzymes evolved to cleave within the recognition site. The studies suggest that this sequestration phenomenon is evolutionary force acting on restriction enzymes. Type III R-M enzymes are multifunctional proteins that exert both methylation and restriction activities. These enzymes require ATP and Mg2+ for restriction. For a number of years, the role of AdoMet in the DNA cleavage reaction by these enzymes has not been clearly defined. Rao's work has shown that DNA restriction by Type III restriction enzymes does not take place in the absence of exogenously added AdoMet. The operation of these restriction enzymes appears to require location of the specific recognition sequence by diffusional searching of the DNA molecule followed by a further, ATP-driven collision of the DNA-bound proteins. Rao investigated protein-DNA interactions in the EcoP15I methylase-DNA complex by biochemical and biophysical methods. Potassium permanganate foot-printing studies revealed that there was a hyper-reactive permanganate cleavage site coincident with adenine that is the target base for methylation. More importantly, to detect DNA conformational alterations within the enzyme-DNA complexes, a fluorescent-based assay was employed. Both EcoPI and EcoP15I DNA methyltransferases require Mg2+ for transferring the methyl group from AdoMet. This is not the case with the well studied type II methyltransferases. Rao's studies suggest that the well-conserved Mg2+ motif is indeed present in both EcoPI and EcoP15I DNA methyltransferases and that binding of magnesium brings about the necessary conformational change that is essential for catalytic activity. His group has engineered the EcoP15I DNA methyltransferase, by substituting an amino acid in the Mg binding motif, to an active sequence-dependent restriction endonuclease that cuts away from its recognition sequence. After years of unsuccessful attempts to co-crystallize E.coli MutH with its cognate DNA by various research groups, Haemophilus influenzae MutH complexed with either unmodified or hemimethylated GATC sequences has been finally crystallized and both structures determined by X-ray crystallography (a collaborative study). Nine students have obtained their PhD under his guidance and six more are being mentored for their PhD degree.
Other Contributions: He also served on the Editorial boards of the journals Resonance (1997-07) and Journal of Biosciences (2001-07).
Awards and Honours: Professor Rao was conferred the PS Sarma Memorial Award (1997), CV Raman Young Scientist Award (1999), Professor YT Thathachari Award for Biological and Medical Sciences (2007), and JC Bose Fellow (2008-2013). He was elected Fellow of the Indian Academy of Sciences, Bangalore, and National Academy of Sciences (India), Allahabad.