Welcome to the Hickson lab

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What is cytokinesis, and why should you care?

 

Cytokinesis is the final step of cell division, when one cell physically separates into two. Textbooks usually depict an actomyosin contractile ring tightening around the cell like a belt. This captures an important part of the process, but not the whole problem: as the division site shrinks, the cell must continually move, reorganize and eventually remodel the membrane and cortex that make up the cell surface.

This is a remarkably old unsolved problem. Scientists have studied cell cleavage experimentally for well over a century, and more than 50 years of molecular cell biology have identified many of the proteins involved. Yet we still lack a satisfying explanation for how all of this machinery works together as a physical system to divide a cell.

Understanding this matters beyond cell division itself. Cytokinesis must be extraordinarily reliable, and its failure can produce abnormal cells with consequences for development, genome stability and disease. It also provides a particularly powerful system in which to ask a much broader question in cell and developmental biology: how do molecular machines generate and control the forces and material rearrangements that change cell shape?

 

 

The physical problem

 

A dividing cell does not simply have to generate force. It has to build a mechanically effective membrane–cortex interface, continually shrink that interface while membrane and cortical material are moving through it, and ultimately reorganize what remains into a narrow connection between the daughter cells.

Our central question is therefore simple: how does one dynamic membrane–cortex system build, close and remodel the division interface?

We want to discover the physical and molecular rules that allow this changing interface to generate force, remain mechanically connected, continually rearrange its material and avoid becoming congested as it shrinks.

 

 

One system, many ways to divide

 

Real cells divide in remarkably different ways. Some furrows close symmetrically from all sides; others advance predominantly from one side. They can close at different rates, use different amounts of the same molecular machinery, and show surprisingly different genetic requirements. Some cytokinetic interfaces disappear rapidly, whereas others become long-lived bridges connecting neighbouring cells.

These differences are often treated as evidence for different mechanisms. We are exploring a simpler possibility: could they instead be different operating regimes of the same basic mechanochemical system?

Our working principle is that a small set of rules governing force generation, mechanical engagement, material loading, rearrangement and relief may explain a surprisingly wide range of cytokinetic behaviours. If so, the diversity of cytokinesis becomes something to explain with a common mechanism rather than a collection of exceptions.

 

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From molecules to mechanics

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Our lab discovered a RhoA GTPase-regulated Anillin–septin pathway that operates alongside the better-known actomyosin machinery during cytokinesis. That discovery helped lead us from asking which molecules are required for cytokinesis to asking what physical jobs those molecules actually perform.

At the centre of cytokinesis is the small GTPase RhoA, a master regulator that is activated at the future division site. RhoA controls several downstream systems, including actomyosin, which generates and transmits contractile force, and Anillin and septins, which organize the membrane-associated architecture of the furrow. We study how these systems work together to control cortical flow, force transmission, membrane–cortex engagement, compression and material rearrangement.

We are especially interested in mechanochemical feedback: molecules create particular mechanical states, but forces, compression and the physical state of the interface can in turn change how its molecular machinery behaves. This is less complicated than it sounds: we are trying to understand how the molecular parts of the cell work together as a physical machine.

 

One continuous cytokinetic process

 

Cytokinesis does not end when the contractile ring finishes closing. As the furrow narrows, it becomes a thin intercellular bridge connecting the two daughter cells. At the centre of this bridge forms a dense structure called the midbody, which helps organize the final stages of cell separation.

Our lab has pioneered the study of how the cytokinetic apparatus is reorganized during this furrow-to-bridge transition. Rather than treating furrow ingression, bridge formation and the midbody as separate biological problems, we ask whether they represent successive states of one continuously evolving membrane–cortex system.

What happens to the material that built the furrow? What is removed, retained, redistributed or repurposed as the interface shrinks? How does a force-generating interface become a stable intercellular bridge and midbody? And why do some such bridges disappear quickly while others persist?

Ultimately, we envision one mechanochemical framework that can follow the cytokinetic interface from its assembly, through closure, to its final transformation or persistence.

 

 

How we do it

 

We combine molecular cell biology, genetics and perturbation with quantitative live-cell imaging and modelling. We work mainly with Drosophila cells and tissues, while collaborating across other experimental systems.

But experiments are only part of the process. We also place considerable emphasis on physical reasoning and on critically revisiting the extensive experimental literature on cytokinesis. More than a century of research has produced many beautiful observations that are not necessarily explained by our current models. We use those observations as constraints.

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We value and nurture careful observation, critical thinking and questions that probe beneath familiar explanations. A good model should not simply fit new data; it should help us understand old observations, expose hidden assumptions and generate better questions that lead to new experiments.

 

Our goal

 

We are trying to understand how cytokinesis actually works.

We want to extend the enduring contractile-ring model into a more complete physical description of cell division—one that explains how force generation, membrane–cortex coupling, material flow and interface remodeling work together throughout the process.

The larger goal is to identify a small set of mechanochemical principles capable of explaining how very different cells assemble, close and transform their cytokinetic interfaces. We suspect that some of these principles will extend beyond cytokinesis, because every cell that changes shape faces a related problem: how can a membrane–cortex interface generate enough mechanical engagement to do work while remaining sufficiently rearrangeable to change shape? Could the same basic mechanochemical rules help explain morphogenesis more broadly?