How Does The Contractile Actomyosin Ring Actuate Cytokinesis?

How cells divide from one to two has fascinated scientists ever since it became clear that cells were the fundamental building blocks for all organisms. Does the force to divide the cell come from within? Or does the division force come from outside the cell? A cell is composed of trillions of molecules. What happens at a molecular scale (1 millionth of a millimeter) and how do collective molecular behaviours power events at a larger scale, such as cell division.

Over the last fifty years it is becoming clear that amoeba, fungi, and animals use a structure, termed the contractile actomyosin ring (CAR), that contains molecules highly related to those that power contraction in the muscle. However, how and whether a muscle contraction like mechanism operates during cell division is debated and changes with the advent of new technology.

The fission yeast, a simple free living organism has become a very attractive tool to investigate mechanisms of cell division, since like our cells, these cells also possess a CAR that is used for cell division. The genes and proteins controlling cell division have been identified from research into this yeast and these contain counterparts in human.

We have pioneered a number experimental approaches in this yeast. Together with high resolution structures of key force producing molecules, we will investigate whether actin-myosin interactions power force generation during cell division, as it does in muscle contraction. Next, we will investigate how tension is created on actin filaments.

Tension is key to moving objects. For example, a rope will become tense when pulled only when another object heavier than the rope is attached to it. We will identify the objects that bind our rope (actin filaments) to understand how actin becomes tense.

Finally, we will determine what work output results from tense actin filaments. We will focus on whether the tension pulls on cell membranes to effect cell division or whether tension causes extrusion of extracellular matrices needed for cell division.

The work will provide an exceptional opportunity to discover cell design principles that are important in basic science, understanding human disease mechanisms, and in the design of synthetic cells for medical and biotechnological purposes. The work will also provide opportunity to train a new generation of interdisciplinary research scholars who may take up employment in academia, industry, and beyond.