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M. S. Shaila
Professor
Ph.D.(IISc, Bangalore,India)
Phone:+91 80 22932702
E.mail: shaila@mcbl.iisc.ernet.in

The major interests of my laboratory are (1) to understand the transcription and replication processes catalysed by the RNP complex of two morbilliviruses-Rinderpest virus and Peste des petits ruminants virus and (2) development of recombinant subunit vaccines. 

The molecular mechanisms governing the negative sense RNA genome transcription and replication are largely unknown in Paramyxoviruses and Morbilliviruses. The genomes of negative strand RNA viruses are tightly encapsidated by the nucleocapsid protein N and this N-RNA functions as a template for viral transcription and replication. Within the virion, the RNA dependent RNA polymerase (L protein) is associated with the N-RNA template through its interaction with the Phosphoprotein P, to form the enzymatically active RNA polymerase which performs transcription and replication of the genome as well as post transcriptional modifications of the mRNAs.  We have endevoured to characterize the transcription/replication complex of Rinderpest virus and Peste des petits ruminants virus and the functions of the component proteins of the RNP complex.

We have demonstrated that the phosphorylation of P protein of Rinderpest virus is essential for transcription and a phosphorylation-null mutant is active in replication of the genome in infected cells as well as in minigenome replication in vivo. Further,an invitro reconstituted transcription system has been established employing recombinant L and P proteins expressed in insect cells and N-RNA template isolated from virus infected cells.

Addition of phosphoryalted P protein results in 2.5 times increased transcription. Addition of either null mutant P or e.coli expressed unphosphorylated P inhibits the transcription by 50%,while in vitro phosphorylated, bacterially expressed P augments transcription by more than two fold.  The focus of the ongoing work is the characterization of capping and methylation activities associated with the L protein of Rinderpest virus.

The second area of research concerns with the development of new generation subunit vaccine for PPR.  Through our systematic investigations, we have been able to identify the immunodominant, neutralizing antibody epitopes as well as helper and cytotoxic T cell epitopes on the Hemagglutinin-neuraminidase protein of PPRV. Further, the HN preotein expressed in transgenic peanut plants in biologically active form ahs been shown to elicit virus neutralizing antibodies in orally immunized sheep. Currently,  we are attempting to generate a chimeric protein (HN-F_ with the B and T cell epitopes of both the protective antigens assembled into the chimera, expressed either in transgenic plants or as Extracellular Virus Particles  of recombinant baculovirus and test their immunogenicity in target animals.

We have recently embarked on a new area of research in collaboration with prof.K.S.sriprakash of Queensland Institute for medical Research,Brisbane,to understand the population structure of Group A and Group G Streptococcus circulating in India ,with a long term goal to investigate the usefulness of a novel peptide vaccine developed in Australia,to combat streptococcal disease in different geographical regions. We are determining the genetic and phylogenetic relationships within Indian isolates using MultiLocus Sequence Typing(MLST).

Selected Publications

M.S.Shaila  ,R. Nayak, Savitha, S. Prakash, David J. McMillan, M R Batzloff, S. Pruksakorn, M.F.Good and K.S.Sriprakash (2007) Comparative in silico analysis of vaccine candidates for Group A Streptococcus predicts that they both may have similar profiles.   Vaccine,  25:3567-3573.

R.Subhashri and M.S.Shaila (2007) Characterisation of membrane association of rinderpest virus matrix protein. Biochemical and Biophysical Research Communications. 355:1096-1101.

J.Vani, R.nayak and M.S.Shaila (2007)  Maintenance of antigen-specific immunological memory through variable regions of heavy and light chains of antiidiotypic antibody. Immunology, 120: 486-496.

J. Vani, J. Justin, R.Nagasuma R.Chandra, R.Nayak and M.S.Shaila (2007) Peptido-mimics of antigen are present in variable region of heavy and light chains of antiidiotypic antibody and function as surrogate antigen for perpetuation of immunological memory. Molecular Immunology, 44:3345-3354.

Paramananda Saikia,M.Gopinath and M.S.Shaila.(2008) Phosphorylation  status of the phosphoprotein P of rinderpest virus modulates transcription and replication fothe genome. Archives of Virology, 153:615-626.