Phase separation creates two distinct liquid phases from a single mixed liquid phase, like oil droplets separating from water. Considerable attention has focused on how the products of phase separation-the resulting condensates-might act as biological compartments, bioreactors, filters, and membraneless organelles in cells. Here, we expand this perspective, reviewing recent results showing how cells instead use the process of phase separation to sense intracellular and extracellular changes. We review case studies in phase separation-based sensing and discuss key features, such as extraordinary sensitivity, which make the process of phase separation ideally suited to meet a range of sensory challenges cells encounter. This article is part of the thematic series, Phase separation of RNA-binding proteins in physiology and disease. The authors declare that they have no conflicts of interest with the contents of this article.

Circadian rhythms are biological oscillations that schedule daily changes in physiology. Outside the laboratory, circadian clocks do not generally free-run but are driven by daily cues whose timing varies with the seasons. The principles that determine how circadian clocks align to these external cycles are not well understood. Here, we report experimental platforms for driving the cyanobacterial circadian clock both in vivo and in vitro. We find that the phase of the circadian rhythm follows a simple scaling law in light-dark cycles, tracking midday across conditions with variable day length. The core biochemical oscillator comprised of the Kai proteins behaves similarly when driven by metabolic pulses in vitro, indicating that such dynamics are intrinsic to these proteins. We develop a general mathematical framework based on instantaneous transformation of the clock cycle by external cues, which successfully predicts clock behavior under many cycling environments.DOI: http://dx.doi.org/10.7554/eLife.23539.001

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Cells respond to stress by blocking translation, rewiring metabolism, and forming transient mRNP assemblies called stress granules (SGs). After stress release, re-establishing homeostasis requires energy-consuming processes. However, the molecular mechanisms whereby cells restore energy production to disassemble SGs and reinitiate growth after stress remain poorly understood. Here we show that, upon stress, the ATP-producing enzyme Cdc19 forms inactive amyloids, and that their rapid re-solubilization is essential to restore energy production and disassemble SGs. Cdc19 re-solubilization is initiated by the glycolytic metabolite fructose-1,6-bisphosphate (FBP), which directly binds Cdc19 amyloids and facilitates conformational changes that allow Hsp104 and Ssa2 chaperone recruitment. FBP then promotes Cdc19 tetramerization, which boosts its activity to further enhance ATP production and SG disassembly. Together, these results describe a molecular mechanism essential for stress recovery, which directly couples metabolism with SG dynamics via regulation of Cdc19 amyloids.

Analysis of seven alleles of the cappuccino gene demonstrates that this formin must both nucleate and processively elongate actin filaments during Drosophila oogenesis. The data also provide mechanistic insight into formin function in general.