First interactive model of human cell division
Mitosis – how one cell divides and becomes two – is one of the fundamental processes of life. The MitoSys Consortium – whose aim it is to understand how diving cells function as a complex system - has now produced a first interactive map of proteins that make our cells divide, allowing users to track exactly where and in which groups the proteins drive the division process forward. This first dynamic protein atlas of human cell division is published in Nature today.
The dynamic cell atlas was developed by Jan Ellenberg’s group at EMBL in collaboration with the lab of Jan-Michael Peters at the IMP. The IMP coordinated the MitoSys project which was funded by the European Commission, as well as a previous consortium called MitoCheck. In 2010, the MitoCheck team identified which genes are required for a human cell to divide as well as which of the proteins made from these genes cooperate as part of protein complexes. But where in dividing cells and at which time these proteins function remained unknown.
“This information is essential for understanding how numerous proteins interact to create a process as complex and dynamic as cell division” says Jan-Michael Peters. “The protein atlas developed by the Mitosys consortium therefore represents an important step towards understanding the dividing cell as a system.”
The resulting Mitotic Cell Atlas integrates these data in an interactive 4D computer model. In this public resource, scientists can freely choose any combination of mitotic proteins and see in real time where and with whom they work during cell division.
Sharing the tools to make more cell atlases
Mitosis Cell division is an essential process of life. When it goes wrong, defects like fertility issues and cancer can occur. Ellenberg: “Besides mitosis, the technologies developed here can be used to study proteins that drive other cellular functions, for example cell death, cell migration or metastasis of cancer cells. 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.”
Looking at disease relevant processes from a dynamic network point of view provides a new perspective to find their critical links, where they can be cut or rewired to strengthen them. To enable more such studies in the future, the experimental methods, the quantitative microscopy platform, and the code to create dynamic protein atlases are now openly available for others to use.
Counting proteins in living cells
The current study looked at HeLa cells, a widely used line of human cancer cells. 28 proteins that are important for mitosis were made fluorescent mostly by CRISPR/Cas genome editing. These proteins were then tracked using 3D confocal microscopy, to see where in the cell they’re located at each point in time. The microscope is so sensitive that it’s even possible to count the proteins, so researchers know now if there are 100, 1000 or 10.000 proteins in a certain location. For all proteins, these data were integrated into an interactive computer model – the creation of which was actually the largest part of the project.
In total, there are about 600 different proteins involved in mitosis in human cells. Completing the dataset for all 600 will eventually allow scientists to more comprehensively understand the transmission of information within a dividing cell, and how decisions – like going from one cell cycle phase to the next – are made.
Cai, Y., Hossain, M.J. et al. Experimental and computational framework for a dynamic protein atlas of human cell division. Nature 561, 411-415 (2018).
The work underlying this publication was supported by grants from the EU-FP7-MitoSys, EU-FP7-SystemsMicroscopy NoE, EU-H2020-iNEXT, as well as by the European Molecular Biology Laboratory