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Meta Heidenreich, Saurabh Mathur, Emmanuel D. Levy (Weizmann Institute of Science, Rehovot, Israel)
To function properly, cells need to organize their content into organelles. Most classically known organelles are surrounded by lipid membranes. However, some organelles, e.g. the nucleolus or heat shock granules, do not require a lipid membrane. Their content is separated from the environment by phase separation, the same process that separates oil and vinegar in salad dressing. Phase separation is a central mechanism of intracellular spatiotemporal organization, and aberrant protein phase separation is associated with diseases, including ALS. We recently developed a synthetic protein system that allows us to probe global changes in protein phase separation, by plotting its phase diagram. We find that quiescent yeast cells show globally enhanced protein phase separation. To identify the responsible genes, we created a genome-wide yeast collection where each strain carries a different genetic knock out, as well as our phase-separation reporter. Knock outs of genes important for maintaining the global protein phase separation propensity lead to detectable changes of our system, enabling us to investigate the genetic regulation of the cytoplasm’s biophysical properties.