Gene essentially and synthetic lethality have so far only been studied extensively in model organisms, such as yeast, in which genes can readily be mutated and mutations can be paired through genetic crossings. In human cells, however, mutation-based approaches have suffered from high inefficiency in the past. The current study represents the first of its kind providing insights into the functional repertoire of essential genes and furthermore the genetic interdependence of selected gene pairs in mammalian cells.
These new insights will be of practical use, aiding scientists in the functional annotation of their gene of interest, choosing suitable approaches to study them and weighing in on feasibility of potential drug targets. Additionally, as a proof of concept the researchers at NKI and CeMM studied a fundamental cellular process to identify synthetic lethal interaction fully based on mutations in human cells. The technique can be applied to various cellular processes including cancer-relevant pathways in order to identify novel potential vulnerabilities in tumor cells. The study has been published in the magazine Science, on October 15, 2015.
Publication:
Vincent A. Blomen*, Peter Májek*, Lucas T. Jae*, Johannes W. Bigenzahn, Joppe Nieuwenhuis, Jacqueline Staring, Roberto Sacco, Ferdy R. van Diemen, Nadine Olk, Alexey Stukalov, Caleb Marceau, Hans Janssen, Jan E. Carette, Keiryn L. Bennett, Jacques Colinge#, Giulio Superti-Furga#, and Thijn R. Brummelkamp#, Gene essentiality and synthetic lethality in haploid human cells. Science, October 15 2015, doi: 10.1126/science.aac7557 (*shared first authors; # corresponding authors)
Funding:
CeMM gratefully acknowledges funding from the Austrian Academy of Sciences, the European Research Council (ERC Advanced Grant i-FIVE), and the Austrian Science Fund (FWF SFB F4711).
CeMM: Essential genes for the survival of human cells
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