Cientistas identificam genes envolvidos na divisão celular em humanos

Scientists Identify Genes Involved in Cell Division in Humans

ScienceDaily (Apr. 6, 2010) — Name a human gene, and you'll find a movie online showing you what happens to cells when it is switched off. This is the resource that researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and their collaborators in the Mitocheck consortium are making freely available, as the result of a study in which they have identified the genes involved in mitosis -- the most common form of cell division -- in humans.

This image of a dividing cell is composed of several microscopy images of human cells in which different individual genes were silenced. The images are placed according to genes’ effects: images for genes that affect chromosomes make up the chromosomes (red), while the mitotic spindle (green) is composed of images for genes that affect it. (Credit: Thomas Walter & Jutta Bulkescher / EMBL)

Published in Nature, their work begins to unravel the molecular workings of one of the most fundamental processes of life: how one cell becomes two.

"Without mitosis, nothing happens in life, really," says Jan Ellenberg, who led the study at EMBL, "and when mitosis goes wrong, you get defects like cancer."

Of the 22,000 genes in each human cell, almost 600 play a part in mitosis, Ellenberg and colleagues found. To uncover which genes are involved in this process, the scientists developed a new method using high-throughput imaging of living cells. They silenced, or inactivated, each of the 22,000 human genes one by one in a different set of cells, and filmed those cells for 48 hours under a microscope. This generated almost 200,000 time-lapse movies of mitosis. Having a person -- or even a group of people -- process such vast amounts of information would be almost impossible, so the scientists created a new computer program that analyses the footage and automatically detects what characteristic defects cells display, and in what order. By grouping genes with similar effects -- for instance, genes which when inactivated led to cells with 2 nuclei instead of one, after division -- they were able to identify genes involved in mitosis, which they confirmed with further experimental assays.

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Nature 464, 721-727 (1 April 2010) | doi:10.1038/nature08869; Received 22 September 2008; Accepted 22 January 2010

Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes

Beate Neumann^1,12, Thomas Walter^1,12, Jean-Karim Hériché^5,13, Jutta Bulkescher¹, Holger Erfle^1,3,13, Christian Conrad^1,3, Phill Rogers^1,13, Ina Poser⁶, Michael Held^1,13, Urban Liebel^1,13, Cihan Cetin³, Frank Sieckmann⁸, Gregoire Pau⁹, Rolf Kabbe¹⁰, Annelie Wünsche², Venkata Satagopam⁴, Michael H. A. Schmitz⁷, Catherine Chapuis³, Daniel W. Gerlich⁷, Reinhard Schneider⁴, Roland Eils¹⁰, Wolfgang Huber⁹, Jan-Michael Peters¹¹, Anthony A. Hyman⁶, Richard Durbin⁵, Rainer Pepperkok³ & Jan Ellenberg²

1. MitoCheck Project Group,
2. Gene Expression and,
3. Cell Biology/Biophysics Units, Structural and,
4. Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany
5. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK
6. Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany
7. Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, Switzerland
8. Leica Microsystems CMS GmbH, Am Friedensplatz 3, D-68165 Mannheim, Germany
9. European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge CB10 1SD, UK
10. Division of Theoretical Bioinformatics, German Cancer Research Center, Im Neuenheimer Feld 267, D-69120 Heidelberg, Germany
11. Institute for Molecular Pathology, Dr Bohr Gasse 7, A-1030 Vienna, Austria
12. These authors contributed equally to this work.
13. Present addresses: MitoCheck Project Group, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany (J.-K.H.); BIOQUANT Centre University Heidelberg, INF 267, D-69120 Heidelberg, Germany (H.E.); 3-V Biosciences GmbH, Wagistrasse 27, 8952 Schlieren, Switzerland (P.R.); Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, Switzerland (M.H.); Karlsruhe Institute of Technology KIT, Herrmann-von-Helmholtz Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany (U.L.).

Correspondence to: Jan Ellenberg² Correspondence and requests for materials should be addressed to J.E. (Email: jan.ellenberg@embl.de).

Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the ~21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.

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