Phase Separation in Living Cells

This book presents the latest cutting-edge research on phase separation. It discusses the benefits and risks of phase separation for living cells from the perspectives of physics, chemistry, biology, and medicine.

Phase separation is a physico-chemical process that induces a single solution of solvent and intrinsically disordered proteins (IDPs) to separate into two phases, one phase containing only solvent and the other containing IDPs in the solvent. A key molecule in phase separation is the intrinsically disordered region (IDR) proteins (IDPs), mostly comprised of RNA-binding proteins (RBPs). One of the major roles of phase separation is to generate condensates, membrane-less organelles including stress granule, Cajal body, and nucleolus.

Biological actions of phase separation in various aspects of science have received increasing attention in recent years. The book consists of four parts; Part I on physics and chemistry includes topics on structural biology of RBP FUS/TLS and chaperone for phase separation, computational approach of phase separation, and chemistry of G-quadruplex of DNA and RNA. Part II on molecular biology presents molecular mechanism of IDR sequence phase separation and potential cellular function of these labile fibers, formation of membrane-less organelles, and roles of noncoding RNAs in phase separation. Part III on biology covers topics from nuclear pore complex, developmental biology regarding force-dependent remodeling, and neurobiology and higher order brain functions. Finally, Part IV on medicine presents condensates and cancer therapy, pathogenesis of neurodegenerative diseases based on IDPs, and responses of microglia to amyloid. The last chapter highlights the latest topic on how the SARS-Cov-2 virus takes advantage of phase separation for its infections.

This book brings together the studies of phase separation in each area in a single volume. The comprehensive approach provides new insights to the research and will benefit the readers by responding to the emerging needs for understanding phase separation.

A multidisciplinary approach to phase separation from physics, chemistry, molecular biology, biology and medicine

Presents a novel view on phase separation control and aggregations

Analyzes neurodegenerative diseases and therapeutics

Autorentext

Riki Kurokawa is a Professor in the Division of Biomedical Sciences at the School of Medicine, Saitama Medical University. He served as a Professor and Chief of the Division of Gene Structure and Function at the Research Center for Genomic Medicine, Saitama Medical University, from 2004 to 2020. His research focuses on gene structure and function, with a particular emphasis on genomic medicineand transcriptional regulation. He has received recognition for his work, including The Award of The Japanese Association for Oral Biology in 1990 and The Nichols Institute New Investigator Award from The Endocrine Society in 1993.

Inhalt
Chapter 1. FUS aggregation by shear stress on pipetting and its suppression by non-coding RNA.- Chapter 2. Basics and recent advances in computational and theoretical methods for understanding the liquid-liquid phase separation.- Chapter 3.Promotion of liquid-liquid phase separation by G-quadruplex DNA and RNA.- Chapter 4. Phase regulation by chaperons.- Chapter 5. Regulation of aggregation of intrinsically disordered protein through phase separation: Risk management of phase separation.- Chapter 6. Molecular mechanisms of phase transition/separation of protein low-complexity sequences.- Chapter 7. Winding and Tangling. An Initial Phase of Membrane-less Organelle Formation (from a viewpoint of Cajal Bodies).- Chapter 8. Formation and function of phase separated nuclear bodies directed by architectural noncoding RNA.- Chapter 9. Force-dependent remodeling of cell-to-cell adhesion through the regulation of phase separation.- Chapter 10. Neuronal RNA granules: Phase separation, dynamics, and higher brain functions.- Chapter 11. Liquid-liquid phase separation in structure and function of nuclear pore complex.- Chapter 12. Phase Separation Orchestrates Cancer Signaling: Biomolecular condensates as a promising target for cancer therapy.- Chapter 13. Regulatory interaction of intrinsically disordered regions of pathogenic proteins in neurodegenerative diseases.- Chapter 14. Functional properties of phase separation and intranuclear complex of FUS in the pathogenesis of ALS/FTLD.- Chapter 15. Functional responses of microglia to amyloid plaques.- Chapter 16. Emerging role of phage separation in COVID-19.