Executive Summary : | Protein aggregation is a complex process that involves the self-assembly of misfolded proteins into soluble oligomers and insoluble aggregates. These aggregates can lead to neurodegenerative disorders like Alzheimer's, Parkinson's, Huntington's, and type-II diabetes. The aggregation process is influenced by various environmental parameters, such as pH, temperature, protein concentration, incubation time, co-solutes, and molecular crowders. Research has focused on preventing protein aggregation at early stages, but most studies have focused on protein's sequence specificity and site-specific mutation. Water, present in the surrounding environment of proteins, plays a significant role in this process. Experimentally investigating the hydration dynamics of protein aggregation is crucial, as many proteins are highly prone to phase separation. Terahertz spectroscopy is a powerful experimental tool for studying the collective H-bond network in water. However, there is a limitation in studying protein hydration explicitly. This proposal aims to understand conformational changes in protein in terms of their hydration using absorption spectroscopy in the THz-FIR region. Other spectroscopic techniques, such as CD, fluorescence, and microscopic techniques like e-SEM, TEM, AFM, and DLS, will also be used to characterize prepared protein aggregates. This project will provide fundamental knowledge about protein aggregation and amyloid fibril formation, potentially helping to prevent related neurodegenerative diseases and contributing to the medicinal and biological chemistry community. |