2019 New Investigator Grant
Huaiying Zhang, Ph.D. Assistant Professor, Department of Biological Sciences, Carnegie Mellon University
The Physics and Chemistry of Liquid Condensation in Live Cells
Survival of all organisms in nature involves millions of complex biochemical reactions occurring simultaneously within protected chemical compartments in the cells of that organism. Some of these compartments are protein droplets condensed from the surroundings like dew formed on grass surfaces on a cool morning. The evidence that supports this idea is that these compartments behave like liquid droplets in cells and key proteins of those compartments condense into liquid droplets in test tubes. It remains unclear how the liquid condensation process happens in live cells, how the chemical composition is defined, and whether being liquid droplets is necessary and important for their functions. This is partially due to the lack of tools to directly manipulate liquid condensation in live cells. We developed a method to induce liquid condensation in live cells using genetically engineered proteins that are responsive to light. In this proposal, we will use this optogenetic approach, in combination with theoretical modeling as well as biochemical and cell biological assays, to address how liquid condensation is regulated in live cells (physics) and how protein droplets recruit components (chemistry). As an example, we work with protein droplets that some cancer cells use to elongate telomeres, ends of chromosomes that trigger cell death when they become too short. Therefore, while the major focus of this multidisciplinary work is to offer fundamental understanding of liquid condensation, it may also provide bases for novel cancer therapy targeting liquid condensation in the future.