Evolutionary analysis of human viruses: Limited information is available on evolution and transmission of human viruses across different geographical regions. Genetic studies have shown mutations in the genes and genome of the viruses. These mutations results in the evolution of new lineages that may have better adaptation to the new host and the new environment. These new lineages develop efficient transmission mechanism with higher rate of human-to-human transmission and enhanced severity of the infection. Genomic information of circulating strains of different viruses from different geographical regions is required to understand their mode of transmission and source of new infection. Therefore, we are working to understand the evolutionary aspects of the viruses that requires continuous monitoring of the circulating variants of human viruses and their movement across the world. Surveillance of human respiratory viruses in Saudi Arabia: Study includes RSV, FLU-A, FLU-B, PIV-1, PIV-2, PIV-3 and adenovirus. We plan to carry out comprehensive global evolutionary analysis of the RSV strains using phylogenetic, Bayesian and Network approaches, entropy, selection pressure glycosylation, and recombination analyses. Their comparison with the strains reported from other parts of the world will provide fundamental genomic information. This data will likely contribute towards the formulation of new control strategies, vaccine design and improved diagnostics. The present proposal will also provide information on influenza virus surveillance that will assist in development of prevention and control measures for future pandemics. Protein Expression, Purification and Characterization: Structural and functional characterization of many proteins are lacking due to their low abundance in nature and therefore inability to purify to homogeneity in sufficient amounts. These proteins are recombinantly produced in our lab in sufficient quantities by overexpression in eukaryotic or prokaryotic system after optimization of their expression level. Protein aggregation studies: Protein aggregation occurs due to its improper folding or misfolding. Aggregation of protein in-vivo leads to various neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease and prion encephalopathies and some other diseases like sickle cell anemia and cystic fibrosis. Improper or misfolding results in alteration of the secondary and/or tertiary structure of normal functional protein. This leads to the formation of protein aggregates of various molecular sizes with different organizations. Different molecular mechanisms are involved in the formation of the various forms of protein aggregates, and numerous theories and models are being put forward to describe protein aggregation. There is no universal phenomenon of protein aggregation available and the mechanism varies significantly for each protein depending on the aggregation conditions. Despite great loss to humanity due to the aggregation related diseases, the molecular mechanisms of protein aggregation are still insufficiently understood.
We plan to decipher the molecular mechanisms of aggregation of few important proteins involved in the initiation and causation of the above-mentioned diseases by Circular dichroism (CD), fluorescence spectroscopy, Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), and various assays using small molecular probes like Thioflavin T, Congo Red, 1-anilinonapthalene 8-sulfonate (ANS) and dot-blot assay using conformational-specific antibodies.