Biomolecular Phase Separation
Cells heavily rely on a simple entropic phenomenon, not only to build their membranes, but also to organize almost every imaginable process in their cytoplasm and nucleus. Liquid-liquid phase separation (LLPS) compartmentalizes specific macromolecules to form droplet-like structures, which closely resemble organelles in a cell. This process has been implicated in the normal functioning of metabolism, transcription, microtubule nucleation, immune cell activation, and signal transduction. It is also why we observe separation of oil and water in salad dressing and underlies how lava lamps work. Not surprisingly, this process has also been linked to a wide variety of diseases such as Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), and even mad cow disease. The Wilson lab utilizes optogenetic tools to study how cells use biomolecular phase separation to integrate and transmit cellular information. We want to know: what is the purpose of phase separation and how does it affect some of the most important biological pathways?
Recently, it has been shown that the destruction complex, which is involved in processing β-catenin within the Wnt pathway, forms a cellular droplet via liquid-liquid phase separation. Ryan Lach has shown that this droplet is heavily correlated with the centrosome, a membraneless organelle. From here, we are investigating how the cell cycle plays a role in this correlation and identifying key proteins in the formation of the destruction complex.
Highlighted Publications
Nucleation of the destruction complex on the centrosome accelerates degradation of β-catenin and regulates Wnt signal transmission. Ryan S. Lach, Chongxu Qiu, Erfan Zeyaei Kajbaf, Naomi Baxter, Dasol Han, Alex Wang, Hannah Lock, Orlando Chirikian, Beth Pruitt, Maxwell Z. Wilson. Proclamation of National Academy of Science. (Download PDF)
Dynamic assembly of the mRNA m6 A methyltransferase complex is regulated by METTL3 phase separation. Dasol Han, Andrew P. Longhini, Xuemei Zhang, Vivian Hoang, Maxwell Z. Wilson, Kenneth S. Kosik. PLOS Biology. (Download PDF)
The proline-rich domain promotes Tau liquid–liquid phase separation in cells. Xuemei Zhang, Michael Vigers, James McCarty, Jennifer N. Rauch, Glenn H. Fredrickson, Maxwell Z. Wilson, Joan-Emma Shea, Songi Han, and Kenneth S. Kosik. Journal of Cell Biology. (Download PDF)
