Dynamic self organization and microscale fluid properties of nucleoplasm
The principal function of the nucleus is to facilitate storage, retrieval, and maintenance of the genetic information. A unique feature of nucleoplasm—the fluid of the nucleus—is that it contains chromatin (DNA) and RNA. In contrast to other important biological polymer hydrogels, such as mucus and extracellular matrix, the nucleic acid polymers have a sequence that encodes both genetic information and strongly influences spatial organization. How does crowding in a sequence specific hydrogel influence spatial organization of the dynamic molecular components responsible for nuclear function? We are becoming increasingly aware of the role of liquid-liquid phase separation (LLPS) in cellular processes in the nucleus and the cytoplasm. Complex molecular interactions over a wide range of timescales can cause large biopolymers (RNA, protein, etc) to phase separate from the surrounding nucleoplasm or cytoplasm into distinct biocondensates (spherical droplets in the simplest cases). I will discuss recent work modelling the role of nuclear biocondensates in neurodegenerative disease and several ongoing projects related to modelling and microscopy image analysis.