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 encoded into DNA and RNA sequences. 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. Recent experiments have shown that during the growth phase of the cell cycle, chromatin condenses in a sequence specific manner into regions within the nucleoplasm, possibly so that functionally related genes are grouped together spatially even though they might be far apart in terms of sequence distance.

At the same time, 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 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.