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Disturbance of Phase Transitions in Neurological Disease

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Tuesday, February 05, 2019
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12:00 pm - 1:00 pm
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Paul Taylor; hosted by Debra Silver
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The Ruth K. Broad Foundation Seminar Series on Neurobiology and Disease

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 membrane-delimited 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 liquid-liquid 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.