Pull Together: our new paper on “The Mesh”

We have a new paper out! You can access it here.

Title of the paper: The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle

What’s it about? When a cell divides, the two new cells need to get the right number of chromosomes. If this process goes wrong, it is a disaster which may lead to disease e.g. cancer. The cell shares the chromosomes using a “mitotic spindle”. This is a tiny machine made of microtubules and other proteins. We have found that the microtubules are held together by something called “the mesh”. This is a weblike structure which connects the microtubules and gives them structural support.

Does this have anything to do with cancer? Some human cancer cells have high levels of  proteins called TACC3 and Aurora A kinase. We know that TACC3 is changed by Aurora A kinase. This changed form of TACC3 is part of the mesh. In our paper we mimic the cancer condition by increasing TACC3 levels. The mesh changes and the microtubules become wonky. This causes problems for dividing cells. It might be possible to target TACC3 using drugs to treat certain types of cancer, but this is a long way in the future.

Who did the work? Faye Nixon, a PhD student in the lab did most of the work. She used a method to look at mitotic spindles in 3D to study the mesh. My lab actually discovered the mesh by accident. A previous student, Dan Booth – back in 2011 – was looking at mitotic spindles to try and get 3D electron microscopy (tomography) working in the lab. Tomography works just like a CAT scan in a hospital, but on a much smaller scale. The mesh is found in the gaps between microtubules that are 25 nanometre wide (1 nanometre is 1 billionth of a metre), this is about 3,000 times smaller than a human hair, so it is very small! It was Dan who found the mesh and gave it the name. Other people in the lab did some really nice work which helped us to understand how the mesh works in dividing cells. Cristina Gutiérrez-Caballero did some experiments using a different type of microscope and Fiona Hood contributed some test tube experiments. Ian Prior at University of Liverpool, co-supervises Faye and helped with electron microscopy.

Have you discovered a new structure in cells? Yes and No. All cell biologists dream of finding a new structure in cells. It’s so unlikely though. Scientists have been looking at cells since the 17th Century and so the chances of seeing something that no-one has seen before are very small. In the 1970s, “inter-microtubule bridges” in the mitotic spindle were described using 2D electron microscopy. What we have done is to look at these structures in 3D for the first time and find that they are a network rather than individual connectors.

The work was funded by Cancer Research UK and North West Cancer Research Fund.

References

Nixon, F.M., Gutiérrez-Caballero, C., Hood, F.E., Booth, D.G., Prior, I.A. & Royle, S.J. (2015) The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle eLife, doi: 10.7554/eLife.07635

—

This post is written in plain English to try to describe what is in the paper. I’m planning on writing a more technical post on some of the spatial statistics we developed as part of this paper.

—

The post title is from “Pull Together” a track from Shack’s H.M.S. Fable album.