Three areas of research that are currently being pursued in our laboratory are
(a) Molecular biology of rotavirus,
(b) Post-transcriptional and translational regulation of eukaryotic gene expression and
(c) Biology of Enteroviruses.
Rotavirus : Rotavirus is the major causative agent of acute infantile gastroenteritis and accounts for about 600,000 deaths worldwide annually. An effective vaccine against rotavirus disease is yet to be developed. A major finding from our laboratory is the identification and characterization of a novel asymptomatic rotavirus strain I321 from a large number of normal newborn children in Bangalore. This unusual virus has evolved in nature by gene reassortment between a G10P11 type bovine rotavirus and a human rotavirus with two genes encoding the nonstructural proteins NSP1 and NSP3 derived from the human virus and the remaining nine genes derived from the bovine parent. I321 has been proposed as a potential live vaccine candidate in humans and is being evaluated in clinical trials. Our studies indicate that age-old Indian traditions, close association of majority of the Indian population with cattle and sociological conditions play a catalytic role in the inter-species transmission of rotaviruses and evolution of novel strains in India. Current studies are focused towards understanding the structure and function of the rotavirus enterotoxin NSP4 and molecular mechanism of NSP4-mediated pathogenesis, mechanism of selective translation of rotaviral mRNAs in the infected cells, molecular interactions between other nonstructural proteins NSP2, NSP5 and NSP6.
Post-transcriptional and Translational regulation of eukaryotic gene expression : Functional expression of a gene can be regulated at multiple levels. Recent studies indicate that post-transcriptional and translational control mechanisms play a central role in the pathway of global as well as specific gene expression. Deregulation of these control mechanisms could lead to human disorders such as cancer. A major mechanism by which tumour cells perpetuate their uncontrolled proliferation is by autocrine production of growth stimulatory factors whose mRNAs are generally not expressed at detectable levels in normal cells. The mRNAs of the majority of the genes involved in cell growth regulation contain long 5’ and/or 3’ untranslated regions (UTRs) and profoundly influence the properties of the mRNA such as stability, translational efficiency and intracellular localization. AU-rich elements are known to influence mRNA stability. Our studies are directed towards understanding the role of AU-rich elements (AREs) and their binding proteins (AREBPs) that influence mRNA stability and splicing.
Enteroviruses : Enteroviruses belong to the family Picornaviridae and constitute a large group of viruses that cause a wide range of diseases in humans and animals such as acute flaccid paralysis, meningitis, myocarditis, acute diarrhea, hand-foot-and-mouth disease, Type 1 diabetes, conjunctivitis etc. A well-known example of this genus is poliovirus. Our current focus is to understand the nature of non-polio enteroviruses causing paralysis, acute diarrhoea and aseptic meningitis, structure and function of the viral genes, molecular mechanism of pathogenesis and the role of unknown ORFs in the biology of the viruses.
The flexible C-terminus of rotavirus nonstructural protein NSP4 is an important determinant of its biological properties. R. Deepa, P. Narayan Sastri, M.R. Jagannath, S. S. Indi, P. Kiranmayee, K. Suguna and C. Durga Rao, J. Gen. Virol. 2008, 89, 1485-1496.
Structure of the extended diarrhoea-inducing domain of rotavirus enterotoxigenic protein NSP4. R. Deepa, C. Durga Rao and K. Suguna. Arch. Virol. 2007, 152, 847-859.
N- and C-terminal cooperation in rotavirus enterotoxin:Novel mechanism of modulation of the properties of a multifunctional protein by a structurally and functionally overlapping conformational domain. M.R. Jagannath, M.M. Kesavulu, R. Deepa, P. narayan sastri, S. Senthil Kumar, K. Suguna and C. Durga Rao. 2006. J. Virol. 80, 412-425.
Rao, C.D., Gowda, K. and Reddy,B.S.Y. (2000) Sequence analysis of VP4 and VP7 genes of nontypeable strains identifies a new pair of outer capsid proteins representing nnovel P and G genotypes in bovine rotaviruses. Virology 276, 104-113.
Rao, C.D., Das, M., Ilango,P., Lalwani, R., Rao, B.S. and Gowda, K. (1995) Comparative nucleotide and amino acd sequence analysis of the sequence-specific RNA-binding rotavirus nonstructural protein NSP3. Virology 207, 327-333.
Das, M., Dunn, S.J., Woode, G.N., Greenberg, H.B. and Rao, C.D. (1993) Both surface proteins (VP4 and VP7) of an asymptomatic neonatal rotavirus strain (I321) have high levels of sequence identity with the homologous proteins of a serotype 10 bovine rotavirus. Virology 194, 374-379.