The results of a huge multinational project to pinpoint all the genes and related proteins essential for cell division are to be made publically available for other researchers to use. The €8.5 million study, which forms part of the European Commission-funded MitoCheck Consortium, involved scientists from eleven research institutes, universities and companies in Austria, Germany, UK, Italy and France, and took five years to complete. The research was published in Nature last week.
The researchers, led by Beate Neumann and Thomas Walter of the MitoCheck Project Group, used a technique known as RNA interference (RNAi) to block the activity of specific genes in dividing cell lines. Our genome operates by sending instructions from DNA in the form of mRNA (messenger RNA) for the manufacture of proteins. During RNAi, a type of molecule called short-interfering RNA (siRNA), together with proteins, binds to a gene's mRNA and destroys it before a protein can be produced.
By using fluorescently tagged chromosomes, the researchers could observe the effect of silencing each gene in real time. In total, 190,000 time-lapse movies of 19 million cell divisions were generated. The entire data set is now free to access on the website www.mitocheck.org.
The findings identified hundreds of genes as being involved in some of the most basic functions of life, including mitosis, migration and survival. Previously only a handful of such genes had been located and, in most cases, their biological function remains poorly understood.
Two accompanying commentaries in Nature highlighted what made the study so exceptional in comparison to previous work.
Jason Swedlow, Professor of Quantitative Cell Biology at the Wellcome Trust Centre for Gene Regulation and Expression, based at the University of Dundee, pointed to the novel way in which the results were validated as one of the things that 'sets [the] study apart from previous work'. Professor Swedlow was not involved in the study.
'Of more than 500 genes that they implicate in mitosis, most are assigned to this process for the first time and few overlap with those identified in previous mitotic screens', he noted.
To verify their results, the researchers tested whether defective cell division could be corrected by adding the mouse equivalent of a gene that had been silenced. The mouse versions of the genes were different enough that they was not silenced by the same siRNAs that targeted the human versions, but they were similar enough to correct cell division in the defective cells, thus demonstrating the genes' significance.
In an accompanying article, Cecilia Cotta-Ramusino and Stephen Elledge, both based in the Department of Genetics at Harvard University Medical School and not involved in the study, called the work a 'landmark contribution'.
'The advantage of such a fine and articulated classification is that it allows predictions to be made about the reason behind new perturbations — for example, those caused by drugs, treatment conditions or disease states — by comparing their phenotypic signatures with those of known genes', they wrote.
Applying the approach to other cell lines, such as those implicated in cancer, was highlighted as an avenue for further research.