Cell division (or "mitosis") is one of the key processes of life. Mistakes during mitosis can cause infertility and mental retardation, and can contribute to cancer. For the most part, mitosis is still poorly understood. Scientists do know that protein kinases – a certain type of enzyme – play a key role, but researchers don't know how these enzymes bring about the important changes in cells that cause them to divide. To understand cell division in a comprehensive manner, the MitoCheck consortium of European scientists will systematically hunt for all genes that are required for division and then check the products of these genes to see how they are regulated by mitotic kinases.
"This project is vital to understanding one of the most basic processes of life - making two cells out of one. Here at EMBL, we will identify which genes are required for mitosis by suppressing them gene-by-gene in live human cells and testing whether they can still divide afterwards," notes Jan Ellenberg, EMBL Group Leader and co-initiator of the MitoCheck project.
To achieve this, EMBL scientists use a method called "RNA interference," where RNA molecules can target and silence specific genes involved in mitosis. Another MitoCheck partner, the Max-Planck Institute of Cell Biology and Genetics in Dresden will provide a vast library of these molecules. About 20,000 genes will be suppressed one-by-one and EMBL researchers will make movies of the cells undergoing division, using sophisticated microscopes developed by Rainer Pepperkok, Jan Ellenberg and Leica Microsystems. Several hundred thousand movies will be produced, filming each group of cells over a 48-hour period, to capture the full impact of silencing particular genes. The task of analyzing the enormous amount of data will be accomplished in a close collaboration of scientists at EMBL and the German Cancer Research Centre (DKFZ).
The end result of the work at EMBL will be a comprehensive list of genes required for mitosis in human cells. But most importantly, for the first time, scientists will know exactly which genes are active during mitosis and what happens in the cell when these genes are suppressed. This information will be used by all the partners in this European project to determine the biochemical regulation of mitotic genes, and to test them as tools for cancer diagnosis. All data produced through MitoCheck will be readily available to the scientific community and the public – through databases at the DKFZ, and at The Wellcome Trust Sanger Institute, another MitoCheck partner.
"This project is an excellent example of a European research network," Jan Ellenberg says. "We have assembled a group of top scientists across Europe, each of whom is contributing an essential piece towards a common goal - understanding mitosis."