Science Snaps: mapping cellular ‘stars’, one molecule at a time

We all start life as a single cell. But how do we get from that to the trillions of cells that make up the human body, each with their own specialised functions?

The answer lies in cell division.

It’s a complicated process and relies on lots of things going exactly to plan. If there are errors along the way then the cell may die or, if it divides uncontrollably, a tumour may form.

The images in this post were made by PhD student Jonathon Hannabuss, and his colleagues at the Francis Crick Institute in London.

But, fascinatingly, while the research is investigating cell division, the pictures don’t actually show cells.

Instead, their lab takes a stripped back approach. This means analysing pieces of cells in isolation, rather than watching an intact cell or groups of them.

Two’s company

The image shows what happened when the team mixed just 2 different molecules. The pink part is a molecule called kinesin-14s and the blue parts are called microtubules.

The molecules aren’t usually those colours, but have been tagged with fluorescent markers to make them glow.

These microtubule asters form when the molecules are placed in glass grooves Courtesy of Jonathon Hannabuss.

“The philosophy of our work is one of looking at cells as collections of interacting parts that are defined by their structure and chemistry,” says Hannabuss.

The idea is to take the different parts out of their natural environment of the cell, and if the conditions are just right, they’ll still work. “If they don’t, then you know you’re missing a vital piece,” he adds.

They hope that investigating these basic interactions without the ‘noise’ of a whole cell will let them focus their aim and get some really fundamental information.

“By studying the molecules of life outside the cell where we can control the environment, we can ask different questions,” says Hannabuss. “It’s about understanding the flexibility and robustness of life.”

Microtubules are thin cellular tubes, a fraction of the width of a human hair. One of their most important jobs is co-ordinating the separation of DNA as a cell divides.

They also control how the cell splits to form 2 new cells, making sure that each of the new cells gets the right DNA in the right amount.

“To understand cancer it’s important to understand how cells divide normally, so that researchers have a map of the system,” says Hannabuss. “Our work will contribute to that map.”

A map to the stars

In cells, microtubules form star-like shapes (called asters) to make sure that that DNA splits correctly between the 2 new cells. And these asters are formed when microtubules grow from centrosomes.

But centrosomes are a complex piece of cellular machinery.

An aster formed in a droplet. Courtesy of Jonathon Hannabuss.

So, in the team’s ‘cell-free’ experiments, kinesin-14s serves as a simpler replacement for the centrosome. “These proteins have ‘feet’ at one end that can walk along microtubules towards the end that, in cells, is usually attached to the centrosome,” says Hannabuss.

The other end of the molecule is called the tail, which sticks to another microtubule. This results in the kinesin-14s molecules gathering microtubules together into star shapes.

Cancer cells often have more DNA and centrosomes than they should, so understanding these interactions might uncover weaknesses that could be exploited to stop the cells growing.

“Cancer cells evolve rapidly – they don’t read the textbooks to find out how they should behave,” says Hannabuss, meaning that they’re different from normal cells.

“This potentially gives cancer researchers a way in – a way of distinguishing cancer cells from our normal cells,” he adds. “But first we need to understand how the systems of the cell actually work.”

Michael