Single-molecule biophysics, Intrinsically disordered proteins, Phase transition in proteins and nucleic Acids, Biomolecular engineering
Our lab focuses on understanding the physical principles of (non) folding and phase behavior of Intrinsically Disordered Proteins (IDPs) using sensitive, high-resolution single-molecule techniques. IDPs account for a significant portion of eukaryotic proteome(30 ‒ 50%). Although they challenge the classical protein structure-function paradigm, it is well established now that the disordered proteome performs important organizational, regulatory, and signaling functions in cells. Furthermore, IDPs are commonly associated with a broad repertoire of human diseases including neurodegeneration and cancer.
IDPs typically display a high degree of conformational plasticity and substantial structural heterogeneity, which severely limits the application of conventional ensemble methods of structural biology to elucidate their properties. Due to this, single-molecule methodologies are critical to study these dynamic biological systems by watching one molecule at a time. In our laboratory, we develop and apply advanced single-molecule fluorescence spectroscopy tools, in combination with fluorescence microscopy, complementary biophysical spectroscopy, and physical modeling. Additionally, we employ a diverse array of chemical and biological methods to interrogate our system of interest. Using this multidisciplinary strategy, we seek answers for how the specific amino acid sequence of IDPs control their individual interaction space in a multi-component system leading to (a) IDP coupled binding-folding behavior that encodes multi-functionality, and (b) IDP self-assembly into biomolecular condensates with tunable material properties. These answers will be critical in deciphering the molecular functions of the disordered proteome and mapping their operational pathways. By understanding IDP molecular properties, we can further explore plausible strategies for (i)ameliorating cellular homeostasis in disease states, and (ii) expanding the scope of bioinspired functional materials.
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