Research Overview

Phase separation

The Hyman lab has a long history studying cell polarity, spindle assembly and positioning, and microtubule dynamics. (To learn more about our past research, visit our Key Discoveries page.) These days, the main goal of the lab is to understand how cells form non-membrane bound compartments. Click here to see short videos explaining our research.

Organization of the Cytoplasm
The cytoplasm of a cell is not an undifferentiated soup of genes; rather, it is structured into hierarchical levels of organization. Proteins are organized into protein complexes, which are further organized into bigger, supramolecular complexes, which are then organized into cellular compartments and organelles. While much is understood about the structure and mechanisms by which proteins interact and form complexes, we are still working to understand the rules by which complexes come together to form compartments.

Compartments: membrane vs. no membrane
Membrane-bound cellular compartments include the Golgi, the ER, and mitochondria. Many talented investigators are studying the formation of these organelles, including 2013 Nobel prizewinner Randy Schekman’s group, which focuses on the organelles in the secretory pathway. However, much less attention has been devoted to the formation of non-membrane bound organelles. These membrane-less compartments include centrosomes, spindles, stress granules, and the nucleolus. How do defined sets of proteins cluster together to form these functional assemblies?

Liquid-liquid phase separations
Work in our lab and others has shown that the cytoplasm contains an emulsion of different liquid protein phases. We first explored this idea after observing that C. elegans P granules, non-membrane bound compartments found in embryos, exhibit classic liquid-like behaviors (Brangwynne et al, Science 2009). The physical implications of liquid-liquid phase separations in the cytoplasm are quite compelling. First, phase separation concentrates materials into compartments as molecules condense out of the cytoplasm. Second, diffusive flux does not operate across a phase boundary, providing a mechanism to isolate the components between two different phases. But because the compartment is still a liquid, its concentrated components can undergo rapid rearrangement, allowing diffusion-limited reactions to take place within the phase boundary.

Current work in the lab
We are actively studying the physical mechanisms of phase separation in the lab, using biophysical, genetic, and chemical methods. The principles of phase separation also inform our understanding of the formation of centrosomes, another active area of research in the lab. Click the buttons below to find out more about our research on phase separations and centrosomes, and also learn more about our current work on mitotic cell rounding, and on the fitness of C.elegans in different temperature environments. Finally, learn how TransgeneOmics in the Hyman lab have transformed our genetic approaches to everything we study.

phase separation centrosomes button cell rounding button temperature button