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Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

Polarity in dividing cells

Coupling cell division and polarity to keep cells organised

The vast majority of cells exhibit ‘cell polarity’ – they typically must distinguish their tops from their bottoms and their front from their backs. In complex organisms like animals or humans, cell polarity must be coordinated between cells to generate functional tissues and organs. Such coordination poses a challenge during embryonic development or in regenerating tissues as cells are continuously growing and dividing. To ensure cells are oriented correctly with respect to one another, cell polarity and cell division must be coupled.

When a cell divides, it generates a flow of material towards its centre, which aids the process of cell division and contributes to the forming boundary between what will become the two new daughter cells. Here the researchers show that this flow of material also transports a key molecule, PAR-3, into this forming boundary. The local flow-dependent accumulation of PAR-3 breaks the internal symmetry of the daughter cells and ensures that the polarity of each daughter cell is oriented properly with respect to its sister. This simple physical mechanism for coupling cell division and polarity may be a general method for keeping cells organised in actively dividing tissues.

Cleavage furrow-directed cortical flows bias PAR polarization pathways to link cell polarity to cell division

Published in Current Biology

Published

An asymmetric pattern of PAR proteins

Going with the flow: how to polarise a cell

Cell polarisation is a fundamentally important ordering process that breaks the internal symmetry of a cell by establishing a preferential axis. The Goehring lab used the nematode worm C. elegans to study why the polarity protein PAR-3 needs to aggregate to efficiently move to the front of the worm embryo. Contrary to previous theories, they found that the size of molecule aggregates did not directly affect PAR-3 movement. Instead, what matters is how tightly these molecules stick to the membrane. This discovery challenges existing ideas about cell transport mechanisms and highlights the role of membrane stability in cellular processes. Defects in cell polarisation can disrupt numerous processes, so developing a systems-level understanding may enable new therapies for developmental defects and cancer.

Design principles for selective polarization of PAR proteins by cortical flows

Published in Journal of Cell Biology

Published

aPKC cycles between functionally distinct PAR protein assemblies to drive cell polarity

Through the use of aPKC inhibitors and genetic mutations, we demonstrate that aPKC cycles between distinct PAR-3 and CDC-42 dependent states, which define, respectively, the ability of the aPAR network to respond to spatial cues and to displace pPAR proteins from the membrane. We further show that cue sensing depends crucially on the oligomeric nature of the PAR-3 state, that the integrity of this cycle is required for coupling of cue-sensing and effector functions of the aPAR network, and that this cycle is enforced by activity of aPKC.

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Published in Developmental Cell

Published

A cell-size threshold limits cell polarity and asymmetric division potential

A key requirement for patterning networks is that the scale of pattern be appropriately matched to the size of the system to be patterned. Through a combination of theory and experiment, we show that failure of the PAR network to scale with cell size restricts stable cell polarity to a specific size range and imposes a minimum cell size threshold for polarity. Experimental alteration of cell size indicates that embryos are sensitive to this size threshold. We thus propose a general strategy by which cells can use intrinsic length scales of patterning networks to enable size-dependent decision making.

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Published in Nature Physics

Published

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Explore a selection of recent case studies that spotlight particular areas of research at the Crick.