ABSTRACT

Phase separation mediates formation of various membraneless organelles, as well as assembly of other cellular structures that control diverse biological processes, including membrane receptor signaling, endocytosis, stress sensing, and both activation and silencing of gene transcription. Phase separation organizes chemically diverse biopolymers, including proteins, nucleic acids, and lipids, to perform complex biochemical and mechanical processes. Consequently, alteration of the process of phase separation, yielding aberrant molecular organization and condensed phases with atypical material properties, is associated with a range of human diseases such as neurodegeneration and cancer. For example, the properties of the nucleolus, the largest membraneless organelle in human cells and a center for ribosome biogenesis and stress signaling, are altered through different mechanisms in ALS and certain cancers. Further, regulation of gene expression, hypothesized to be controlled through condensation of genes, transcription factors and RNA polymerase II, may be altered by phase separation-prone oncoproteins in certain leukemias. We will discuss our efforts to understand how phase separation contributes to biological processes in normal cells and how these processes are altered in disease, including neurodegeneration and cancer.