Research in the Deshmukh is focused on characterizing the structure and conformational dynamics of biological macromolecules using a range of biophysical methods, including heteronuclear NMR spectroscopy, fluorescence spectroscopy, transmission electron microscopy, small angle X-ray scattering, and mass spectrometry. In particular, the group is interested in the development and implementation of new solution NMR methods to explore protein folding and misfolding, and human diseases including HIV, Alzheimer’s, and diabetes.
Solution NMR spectroscopy
Solution NMR spectroscopy enables researchers to elucidate three-dimensional structures of macromolecules in their native environment, providing quantifiable and calculable links between structure, function, and activity. It is also unique in its ability to elucidate a vast range of motions that are exhibited by biomolecules, which provides vital information regarding ligand recognition, protein assembly, conformational dynamics, protein folding, and many other essential cellular processes. This knowledge is critical for understanding disease processes at the molecular level, and for the development of new pharmaceuticals.
Protein folding, misfolding, and amyloids
Amyloids are commonly viewed as irreversible end-products of uncontrolled aggregation events associated with proteinopathies, including Alzheimer’s and Parkinson’s diseases. Recent discoveries of functional amyloids have challenged this perception by elucidating the physiological roles of amyloids and their ubiquitous distribution in lower and higher-order organisms. The Deshmukh group seeks to understand the mechanistic underpinnings of amyloid formation and how eukaryotic cells generate functional amyloids without succumbing to pathology and exploit their useful properties.