“Disturbance of Phase Transitions in Neurological Disease”

J. Paul Taylor, MD, PhD, Investigator, Howard Hughes Medical Institute Chair, Department of Cell and Molecular Biology Edward F. Barry Endowed Chair of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN Eukaryotic cells partition their contents into numerous specialized structures termed organelles that create microenvironments to facilitate specific functions. Membrane-less organelles such as ribonucleoprotein (RNP) granules differ from classical membranedelimited compartments in that they behave like liquid droplets that rapidly assemble and disassemble in response to changes in the cellular environment. Membrane-less organelles include nucleoli, Cajal bodies, speckles, paraspeckles, and PML bodies in the nucleus, as well as P bodies, stress granules, and RNA transport granules in the cytoplasm. Paradigm-shifting advances over the past year have revealed that diverse membrane-less organelles assemble via liquidliquid phase separation (LLPS) of low sequence complexity domains that are particularly enriched in RNA-binding proteins. In my talk I will present evidence generated in my lab over the last 8 years indicating that the defect underlying many forms of ALS and FTD is disturbance of phase transitions that alters the dynamic properties of membrane-less organelles.