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General description: The major focus of the lab is the functional identification of novel cancer-relevant genes. The completion of the sequencing of the human genome indicates that it encodes 30-40.000 genes. However, at present the information regarding specific gene function is quite limited.
Since such information is crucial for the understanding of normal growth control and its deregulation in cancer, the lab has developed several functional genetic approaches to obtain information regarding gene function via high-throughput screens. In general, genetic screens represent an unbiased approach to identify genes that act in specific cellular pathways.
We have developed both gain-of-function genetic screens (with retroviral cDNA expression libraries) and vector-based as well as synthetic RNA interference to carry out large-scale loss-of-function genetic screens in mammalian cells.
Role in RUBICON: Reversible modification of proteins by ubiquitin (Ub) and ubiquitin-like moieties (Ubl) has emerged as a key regulatory step in many cellular processes. While Ub- and Ubl-conjugation is well-characterized, little is known about the Ubl- and Ub-specific proteases (deubiquitinating enzymes (DUBs)), which remove these modifications from cellular substrates. In order to study the functions of DUBs in cancer-relevant pathways, the lab has developed a collection of short hairpin RNAvectors targeting this gene family. As members of the RUBICON network we will continue to perform DUB screens, identifying new pathway regulators, and we will also make our library accessible to other members of RUBICON.
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Annette Dirac, Post-doc (Rene Bernards’ Group)
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