Biology subjects

Roy, P.

Publications and source records attributed to Roy, P..

3 recordsLinked to original sources

bioRxiv2018

Rational Design of Peptide Vaccines for the Highly Lethal Nipah and Hendra Viruses

The Nipah virus disease is a lethal infection that has led to 40% to 75% fatalities in Malaysia, Bangladesh and India. The reports of human-to-human transmission documented in Bangladesh has raised the specter of pandemic potential and has caused the World Health Organization to list the Nipah virus as one of the pathogens to be considered for development of drugs and vaccines on urgent basis, neither of which exist against the Nipah virus as of now, although many proposals have been made and trials initiated. Given that there are established country-specific differences in the virus effects and fatalities, meeting the sudden need for a vaccine in case of an epidemic will require design, development and preparation for a peptide vaccine. Thus, we propose a protocol for creating peptide vaccines that can be tailor-made for these specific countries, an approach which is being advocated for the first time. Here, we analyze the surface proteins, Fusion protein and Glycoprotein, of the strains currently affecting the three countries on a large scale and determine the specific country-based epitope differences.

bioinformatics↗

bioRxiv2018

Immune differentiation regulator p100 tunes NF-κB responses to TNF

Stringent regulation of TNF signaling prevents aberrant inflammation. TNF engages the canonical NF-{kappa}B pathway for activating the RelA:p50 heterodimer, which mediates specific expressions of pro-inflammatory and immune response genes. Importantly, the NF-{kappa}B system discriminates between time-varied TNF inputs. Negative feedback regulators of the canonical pathway, including I{kappa}B, are thought to ensure transient RelA:p50 responses to brief TNF stimulations. The noncanonical NF-{kappa}B pathway controls a separate RelB activity associated with immune differentiation. In a systems modeling approach, we uncovered an unexpected role of p100, a constituent of the noncanonical pathway, in TNF signaling. Brief TNF stimulation of p100-deficient cells produced an additional late NF-{kappa}B activity consisted of the RelB:p50 heterodimer, which distorted the TNF-induced gene-expression program. Periodic TNF pulses augmented this RelB:p50 activity, which was reinforced by NF-{kappa}B-dependent RelB synthesis. In sum, the NF-{kappa}B system seems to engage distantly related molecules for enforcing dynamical and gene controls of immune-activating TNF signaling.

systems biology↗

bioRxiv2018

Broad geographic sampling reveals predictable and pervasive seasonal adaptation in Drosophila

To advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions and we find a broad concordance between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. Our results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation in Drosophila.

evolutionary biology↗