3 September 2020
New biosensor measures activity of control enzyme MPS1
New research published in Current Biology looks at MPS1 enzyme activity in colorectal cancer cells using a newly developed biosensor that can accurately depict the activity of the MPS1 enzyme in living cells.
Researchers from the group of Oncode Investigator Geert Kops (Hubrecht Institute) have developed a biosensor that can precisely depict the activity of the MPS1 enzyme in living cells. MPS1 is responsible for accurate distribution of DNA during cell division; errors in this process can lead to cancer. Using the new biosensor, the researchers discovered that the MPS1 enzyme is significantly less active in colorectal cancer cells. The results were published in the scientific journal Current Biology on the 3rd of September.
During cell division, it is important for cells to duplicate their genetic material and distribute it equally over the two resulting daughter cells. This way, both new cells encompass the exact same genetic information. The occurrence of errors in the distribution of the genetic material – also called chromosome segregation – can lead to cancer. Certain enzymes are responsible for safeguarding the process of chromosome segregation, among which is MPS1. “We are very interested in this enzyme: how does MPS1 control its location in the cell, ensure it is activated in the right way and manage the activation or deactivation of signals that are important for correct chromosome segregation?”, asks Geert Kops, principal investigator in this study.
For this project, the researchers gained inspiration from other studies using biosensors. Biosensors change fluorescence, or color, once they interact with the enzyme to which they are programmed to respond. This enables the researchers to precisely measure enzyme activity. “We have developed a biosensor that responds to MPS1 but not to similar enzymes, which proved to be a technical challenge. Timo Kuijt, the PhD-candidate who worked on this project, spent two years making the sensor. However, in return, the biosensor has provided many great research opportunities" says Kops.
The researchers placed the biosensor at different locations in the cell. “The sensor gives spatio-temporal information about the activity of MPS1, which is a first. We were able to measure when the enzyme is active at various locations in the cell, but also when the activity reduces”, adds Kops.
Even though the study originates from a fundamental interest in the functioning of this specific enzyme, the researchers also saw valuable opportunities for studying cancer. They therefore placed the sensor in colorectal cancer cells to measure MPS1 activity and found that MPS1 is significantly less active in these cells compared to healthy cells. Kops: “This suggests that there is something wrong with MPS1 activity in cancer cells, but we do not know whether this is a cause for or consequence of the development of cancer. What would for example happen if we were to normalize MPS1 activity in cancer cells? We aim to investigate this question – and many others – in further studies.”
A biosensor for the mitotic kinase MPS1 reveals spatiotemporal activity dynamics and regulation. Timo E. F. Kuijt, Maaike L. A. Lambers, Sonja Weterings, Bas Ponsioen, Ana C. F. Bolhaqueiro, Debbie H. M. Staijen and Geert J. P. L. Kops. Current Biology 2020.
Geert Kops is group leader at the Hubrecht Institute, professor of Molecular Tumor Cell Biology at the University Medical Center Utrecht, Oncode Investigator and Scientific Director and head of Oncode Institute.