POSTDOCTORAL BIOINFORMATICIAN INTEGRATIVE, PATHWAY-BASED MODELS FOR RESPONSE PREDICTION IN COLORECTAL CANCER The development of novel anti-cancer agents that target growth signaling pathways presents many challenges, the most demanding being to identify which tumours are dependent on a given pathway and thus the patient group most likely to respond to therapy. Current approaches rely on measuring individual markers that act as surrogates for pathway status, but give little information on activation state or cellular addiction. This project will develop in silico techniques to integrate and analyse genetics, genomics and protein level data with a focus on the PI3K and MAPK signaling networks. A unique data set has been specifically assembled for this project consisting of - whole genome transcript data (Affymetrix HG_U133 Plus 2), - whole genome high resolution copy number data (Agilent Human 244K), - selected protein expression data using a reverse-phase array platform, plus - mutation status of genes frequently modified in colorectal cancer. This comprehensive molecular characterisation has been completed on 58 colorectal cell lines and 64 primary colorectal tumors. In addition, the pharmacological sensitivity of the colorectal cell lines to a range of targeted drugs is know. Specific objectives for this project include - Model pathway status in colorectal tumours and cell lines through integrative analysis of the molecular data - Intersect tumour and cell line models to assess how accurately cell lines recapitulate human disease at the pathway level - Stratify colorectal tumours and cell lines on the basis of predicted pathway activation The results from this project will not only increase knowledge of colorectal cancer and molecular stratification techniques, but provide valuable information on the utility of cell line models for generating pre-clinical hypotheses for personalised medicine. CANDIDATE REQUIREMENTS We seek an individual with knowledge of both informatics and biology, with particular interest in translating complex data into testable hypotheses. Candidates should fulfill the following criteria: - PhD (or equivalent) in one of the following areas: bioinformatics, engineering, computer science, statistics or physics. - Knowledge of biology, particularly signaling pathways. LOCATION The position is primarily embedded within the Bioinformatics and Statistics group led by Dr Lodewyk Wessels (http://bioinformatics.nki.nl) at the Netherlands Cancer Institute, Amsterdam. The candidate will also spend time in the AstraZeneca Oncology Informatics group, Alderley Park, UK led by Dr Tim French. CONTACT DETAILS Please contact Dr. Lodewyk Wessels, tel. +31 20 512 7987 or e-mail: l.wessels@nki.nl or Dr Tim French, Oncology Informatics, Discovery Medicine, tel. +44 1625-519922 or e-mail: Tim.French@astrazeneca.com. 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 to obtain further information. http://bioinformatics.nki.nl CLOSING DATE 15 September 2009