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My work is mainly focused on understanding the virus evolution in the presence of immune responses and how immune response evolves over time after antigen exposure.
While studying viral evolution and immune responses, I became interested in immune cell interactions, especially cellular rearrangement during immunological synapse formation. I would like to pursue further research to understand them in depth using fluorescence microscopy techniques.
Dengue virus diversity
Dengue is a mosquito-borne disease with four closely related virus serotypes (DENV-1-4). About one-third of the global dengue cases are estimated to be from India. Yet we have a very poor understanding of the dengue virus diversity and evolution in the country. We analyzed all the published dengue sequences and our analysis highlights
The co-circulation of all DENV serotypes in India with cyclical outbreaks every 3-4 years.
Significant intermixing of dengue viruses within India and between Asian countries.
Differences in epitopic regions in Indian dengue strains compared to the major vaccine candidates, suggesting a need of local vaccine design as opposed to a single global vaccine.
Check out these publications to know more
Evolution of dengue virus in the presence of cross-reactive antibodies
Cross-reacting dengue antibodies from a prior infection from one serotype can protect or enhance infection from other serotypes. This can force the emergence of new dengue variants that find ways to escape the immune action or take advantage of it. In endemic countries like India, high rates of previous dengue infection can drive the evolution of dengue serotypes in complex ways.
Our analysis highlights
Interlinked inter- and intra-serotype evolutionary dynamics.
Several lines of evidence pointing to the interlinked dengue evolution driven by the underlying population-level natural immunity in India.
Emergence of rapidly evolving DENV4 lineage (DENV-4-Id) in South India with higher seroprevalence of DENV-1 and DENV-3.
DENV-4-Id has acquired residues corresponding to Indian DENV-1 and DENV-3 strains.
For more details
Humoral immune response to COVID-19 infection or vaccination
We developed in-house ELISA assays to quantify the antibody levels (IgG and IgA) against the spike trimer, RBD and nucleocapsid proteins. Spike trimer showed the best sensitivity among all the spike protein antigens. We employed the ELISA assays to assess the evolution of antibody response after vaccination/ natural infection.
Key results:
Antibody levels reached peak levels within 2-3 weeks of infection or vaccination.
Antibody levels waned over three months but were boosted significantly after the second dose of the vaccine in the case of COVID-19 naïve individuals.
The hybrid immunity (natural infection + vaccination) generated significantly higher antibody titers than the two doses of vaccine.
Longer time interval between antigen exposure gives higher boost in antibody response.
Following article describes the development of the Spike based serology assay
Assembly of filamentous bacteriophage on live bacterial cell
High aspect ratio M13 phage (~1 μm in length and 6-8 nm in diameter) infects and replicates inside Escherichia coli (E. coli) bacteria carrying F-pilus. Newly formed phage coat proteins assemble on the phage DNA in the bacterial inner membrane while the phage particle ejects out of the cell without lysing the cell. We employ fluorescence-based single-molecule tracking and super-resolution imaging (dSTORM) to probe the phage assembly at a single-cell level.
Key observations:
The bacteriophage assembly occurs mostly on the dividing bacteria.
Assembly sites are not uniformly spread across the bacterial surface.
These projects wouldn't have been possible without wonderful collaborators
Dr. Chitra Pattabiraman (Infectious Disease Research Foundation)
Dr. Arun Sankaradoss (National Centre for Biological Sciences)
Prof. Sudhir Krishna (National Centre for Biological Sciences)
Prof. Guruprasad Medigeshi (Translational Health Science and Technology Institute)
Dr. Uma Chandra Mouli Natchu (St. John's Research Institute)
Dr. Sharath Nagaraja (ESIC Medical College)
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