Computational Cancer Biology Positions
COMPREHENSIVE COMPUTATIONAL MODELING FOR COMBINATION TREATMENT DESIGN PROJECT OUTLINE All cancers arise due to alterations in their genomes. Although insight into the genetic lesions in tumors by genome sequencing does already assist in selecting some drug regimens, it rarely results in disease eradication due to the emergence of drug-resistance. More sophisticated combination therapies in which several oncogenic pathways are targeted simultaneously could alleviate this problem. However, at present we are unable to extract and interpret the necessary information from tumors to predict which drug regimen will be most adequate. In this project we will collaborate with Welcome Trust Sanger Center and employ the 1000 cancer cell line data set to tackle this problem. This data set comprises large-scale molecular characterization and cancer drug screening of all cell lines for 400 anti-cancer drugs. The molecular data currently consists of gene expression, copy number (SNP-6), and whole exome sequencing data and is being expanded. The successful candidate will work closely with scientists at the Welcome Trust Sanger Center and the Netherlands Cancer Institute and employ computational approaches to mine this rich, valuable pre-clinical resource. Potential results include 1) new molecular biomarkers to identify sensitive populations 2) repositioning of existing drugs in other tumor types and 3) potential drug combinations aimed at overcoming resistance mechanisms. Hypotheses emerging from these analyses will be validated in model systems and where possible in clinical settings. CANDIDATE REQUIREMENTS – EDUCATION AND EXPERIENCE We are seeking highly motivated Postdoc or PhD candidates with a degree in bioinformatics, computer science, mathematics or physics and with a strong cancer biology interest. Preferably applicants should have a documented experience in analyzing high-throughput genomic data. The candidate needs to be proficient in common bioinformatics scripting and programming languages. Fluency in spoken and written English is a strong requirement. LOCATION The project involves groups at the Netherlands Cancer Institute, Amsterdam (Rene Bernards, Molecular Carcinogenesis, and Lodewyk Wessels, Computational Biology) and the Welcome Trust Sanger Institute (Mathew Garnet and Ultan McDermott, Cancer Genome Project). This position will be embedded in the Computational Biology Group lead by Lodewyk Wessels. 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 3 February 2013
CombatCancer: 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 • Strong documented experience in analyzing patient and preferable high throughput data. • Strong background in computer hard- and software systems • Proficiency in programming languages such as Java, Perl or Python, as well as Linux systems. • Experience in liaising between computational and molecular biologists as well as clinicians • Fluency in spoken and written English is a strong requirement 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
participants (1)
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Lodewyk Wessels