Computational cancer biology for personalized medicine

For an ambitious joint Synergy-ERC program the Netherlands Cancer Institute (NKI, Amsterdam, The

Netherlands) and the Wellcome Trust Sanger Institute (WTSI, Hinxton, UK) invite excellent and ambitious

postdocs and PhD students with expertise in computational biology to apply. It is the ambition of this

international team to unravel the genomic and phenotypic complexity of human cancers in order to identify

optimal drug combinations for personalized cancer therapy that will be further explored in our existing clinical

trial networks. The expected duration of the project is 6 years. The computational biologists will collaborate

closely with experimentalists and will focus on the following tasks:

 Mapping the mutational landscape of tumors. We will employ exome sequencing data from over 5000

tumors from 12 different tumor types to identify recurrently mutated, recurrently co-mutated and mutually

exclusively mutated genes as well as frequently mutated pathways or sub-networks. Employing results from

mouse forward genetic screens we will characterize the mutational landscape in mice and overlay this

landscape with the human mutational landscape in order to produce a filtered, high confidence map of the

cancer mutational landscape. This landscape will reveal putative cancer vulnerabilities (e.g. frequently

mutated pathways) that can be attacked in an orchestrated fashion by targeted (combination) therapies.

 Leveraging data from large scale molecular and drug sensitivity characterization of cell lines. The

CGP program with the WTSI recently completed the molecular (RNAseq, DNAseq, methylation) and

pharmacological (400 anti-cancer drugs) profiling of 1000 cancer cell lines. In addition, drug combination

screens are being performed for a subset of the 400 drugs. We will leverage this data to map the cancer

vulnerabilities identified in tumors to drug response using, amongst other, logic rules. These logic rules will

aid the discovery of novel combination treatments that will be validated in cell lines and mouse models.

 Requirements

• Degree in bioinformatics, computer science, mathematics or physics

• A strong cancer biology interest and/or background

• Proficiency in programming languages such as Java, Perl or Python, as well as Linux systems.

 Contact details. Please contact Lodewyk Wessels, tel. +31 20 512 7987 or e-mail: l.wessels@nki.nl. When

applying, please ensure you include a CV, list of publications and the names and addresses of at least two

persons that can be approached as references. Also see bioinformatics.nki.nl for further information.

 Closing date: 1 October 2013