The phase transition process of liquid-liquid demixing organizes proteins and RNAs into liquid compartments in cells. We study how this process promotes cellular functions in healthy cells and how misregulation of it leads to cancer. Building on this, we engineer synthetic organelles by taking inspiration from cells and develop therapeutic strategies by targeting phase transition in cancer cells.
Investigate functional significance of phase transition in cells
We developed optogenetic tools to manipulate phase transition in live cells so we could observe the functional consequences. We focus on telomere DNA synthesis in cancer cells, a biochemical reaction that all cancer cells rely on for immortality. We demonstrated that condensation of liquid droplets on telomeres of telomerase-free cancer cells clusters telomeres to provide templates required for homology-directed DNA synthesis. We ask how the nucleation process is regulated, how the components are recruited , how the material properties are controlled and how they contribute to telomere DNA synthesis and cancer cell growth.
Reversal of telomere clustering induced by liquid condensation after dissolution of liquid droplets
Engineer synthetic organelles
Using a bottom-up approach to construct liquid organelles will advance our understanding of liquid condensation in cells and inspire new applications exploiting phase transition. With advanced biophysical characterizations such as microrheology and fluorescence correlation spectroscopy, we investigate how the material properties and chemical composition of liquid organelles are defined and how they affect biochemistry within.
Beads (red) imbedded in a droplet (green labels protein, RNA is not labeled) to probe droplet properties with microrheology
Control phase transition for cancer therapy
We demonstrated that liquid condensation contributes to telomere elongation in telomerase-free cancer cells by clustering telomeres to provide templates required for homology-directed telomere DNA synthesis which cancer cells rely on for immortality. We set out to develop cancer therapies to inhibit telomere synthesis by combining experimental and theoretical approaches to manipulate phase behavior.
Phase diagram to map and manipulate for cancer therapies