Mitosis, the division of a single cell into two identical cells, is part of the natural process of a cell’s life cycle. In the human body, this fundamental process has two main purposes: to repair damaged tissues and help the body to grow. To make this possible, hundreds of different proteins work together in a single cell, driving its various processes. Proteins help the cell keep its shape, control particle movement and repair the cell if it’s damaged. Their role in cell division is also especially important, since they control all parts of the process, from beginning to end.
While up to now most research laboratories have focused on single proteins in living cells, scientists working on the EU-funded iNEXT and CohesinMolMech projects have taken a more comprehensive approach. By moving beyond individual proteins and studying the networks of proteins active in living human cells, they have succeeded in creating the first dynamic protein model of human cell division.
A real-time protein atlas
Named Mitotic Cell Atlas
, the model uses 4D image data to demonstrate the changes that occur in human cells during the 5 mitotic phases: the interphase, prophase, metaphase, anaphase and telophase. By entering any combination of up to seven proteins, users will be able to see the relevant cell division process in real time.
As the project’s researchers explain in a paper
published in the journal ‘Nature’, the model can also be used to study the role that proteins play in other cellular functions, such as cell death or the metastasis of cancer cells. To create their dynamic protein atlas of human cell division, the scientists used a generic approach. The approach can therefore be applied to mapping and mining dynamic protein networks that cause cell division in different cell types. “By looking at the dynamic networks these proteins form, we can identify critical vulnerabilities, points where there’s only one protein responsible to link two tasks together without a back-up,” says co-author and European Molecular Biology Laboratory (EMBL) senior scientist Jan Ellenberg in a press release
posted on the project partner’s website.
Twenty-eight proteins down, hundreds to go
The new 4D model was used to integrate data on fluorescently knocked-in mitotic proteins taken from HeLa cells, an immortal line of human cancer cells commonly used in scientific research. Overall, 28 proteins that play an important role in mitosis were tracked using 3D confocal microscopy
to locate their position in the cell at different points in time. But many more years of work are required before the team can create a data set for the 600 or so proteins that drive mitosis in human cells. “In the long run, a full overview of all the cell’s proteins will allow us to see how different important processes of life, like cell division and cell death for example, are linked to one another. You can only understand this from a network point of view,” says Stephanie Alexander, co-author and Research Manager at EMBL’s Ellenberg group in the same press release.
iNEXT (Infrastructure for NMR, EM and X-rays for translational research) is working to translate fundamental structural biology research into bio-scientific applications. Through its research, CohesinMolMech (Molecular mechanisms of cohesin-mediated sister chromatid cohesion and chromatin organization) aims to advance our understanding of cell division, chromatin structure and gene regulation.
For more information, please see: iNEXT project website