PSDL RESEARCH

Protein Structural Dynamics

Structural dynamics are essential for understanding every biological mechanism—ranging from chromosome organization and biomolecular phase separation to membrane-protein function—and are the focus of our work in the Protein Structural Dynamics Lab (PSDL).

We employ the novel HS-AFM technique to directly visualize protein movement and dynamics, and complement this with single-molecule approaches such as fluorescence microscopy and magnetic tweezers to probe protein dynamic behaviors.

Chromosome Organization

A chromosome is organized after 2 meters of DNA is replicated and compacted into a chromosome in a living human cell. Each chromosome consists of two sister chromatids, and the two sister chromatids are segregated into two daughter cells to transfer equal amounts of genetic information into two daughter cells. This process is vital for the proliferation and growth of living things. Moreover, this huge amount of DNA is involved in numerous biological processes such as DNA replication, RNA transcription, DNA repair, and chromosome segregation. Therefore, the genome organization in the nucleus should be very precise in 3D space to coordinate cellular processes to prevent any errors in the biological processes. Failure can cause serious diseases such as cancer or developmental disordered diseases. We aim to unravel the molecular mechanism of chromosome organization for various cellular processes by understanding the structural dynamics of chromosomal proteins.

Intracellular Phase Separation

Phase separation phenomena are involved in myriad biological processes such as chromosome organization, membraneless compartments formation, nuclear pore complex formation, and membrane receptor clusters formation. Generally, phase-separation phenomena in a cell are defined as concentrated nonstoichiometric assemblies of biomolecules that can form via spontaneous or driven processes sharing many of the hallmarks of phase transition. In addition, as gas, liquid, and solid states exist in materials depending on the strength of inter- and intra-molecular interaction, liquid or gel states of biomolecules exist in a living cell. However, what determines the inter- or intramolecular interactions to be a liquid phase or gel phase is not clearly understood in the biological system; hence how the protein interacts together to induce phase separation needs to be understood.

Membrane proteins

Membrane proteins are a part of or interact with the cell membranes, and approximately 40 % of all cellular proteins reside on lipid membranes, where they play critical roles in metabolic functions and regulating the transfer of information and materials into and out of the cell. Membrane proteins govern many important cellular processes such as nutrient uptake, drug efflux, sensory physiology, immunity, and neuronal communication. It has been widely acknowledged that membrane proteins are also central components in numerous disease states and host-pathogen interactions. Therefore, many membrane proteins are prime drug targets because they perform essential processes in the cell including controlling the flow of information and materials between cells and mediating activities like hormone action and nerve impulses. Therefore, the structural dynamics of membrane proteins is important to lead to new and improved pharmaceutical treatments for a wide range of illnesses such as heart disease, cancer, and infectious diseases.