BIOINFORMATICS POSTDOC Topic: Pathway-based tumour characterisation by alignment against cell panels along multiple molecular dimensions. Research: Astra Zeneca Oncology has constructed large cell panels to serve as in vitro models for drug response. These cell panels have been extensively characterized by mutation analysis, mRNA expression, aCGH, response to a wide variety of drugs, micro-RNA expression and phosphoprotein characterization. In parallel, the same measurements are being performed on a collection of colorectal samples. In this project two aims are pursued. First, a comparative analysis will be performed between the cell line data and the tumor data to determine the multi-dimensional molecular states spanned by the cell lines and whether these states faithfully recapitulate the space spanned by a representative and clinically relevant selection of tumor samples. Guided by this mapping and by following a pathway-based approach, integrative modeling will be applied on the cell line panel data to construct models predictive of resistance. Job description: The successful candidate will be responsible for the bioinformatics analysis of the cell line and tissue data. More specifically, these tasks include 1) constructing a comprehensive gene list of the PI3K and ERK network; 2) Molecular characterisation of the colorectal cell panel and tumour samples through integrative analysis of the various data sources within the space spanned by the identified network genes and 3) Pathway-based alignment of cell panel to tumours to determine the extent to which the cell panel recapitulates the heterogeneity in the tissue set. Location: The position is embedded within the Bioinformatics and statistics group lead by Dr Lodewyk Wessels (http://bioinformatics.nki.nl) at the Netherlands Cancer Institute, Amsterdam and the Oncology Informatics group, Discovery Medicine, Astra Zeneca, Alderley Park, UK lead by Dr Tim French. We plan to have regular meetings, and the postdoc will also spend time at both locations. Requirements: Candidates should fulfill the following criteria. - MSc or PhD in one of the following areas: bioinformatics, engineering, computer science, statistics, physics, biotechnology, or biology. - Knowledge of fundamental aspects of cancer biology, especially signalling pathways. - Knowledge of fundamental aspects of computer science (algorithms and data structures, programming languages). - Knowledge or experience of informatics. - Knowledge of statistics, artificial intelligence or bioinformatics is highly desirable. Conditions of Employment: The successful candidate will be employed by the Netherlands Cancer Institute. The employment conditions follow general employment rules as laid down in the 'CAO' for hospitals. The salary will be determined depending on education and experience. Contact and Applications: Dr. Lodewyk Wessels, tel. +31 20 512 7987 or e-mail: l.wessels@nki.nl or Dr Tim French Discovery Medicine, Cancer Bioscience, tel. +44 1625-519922 or e-mail: Tim.French@AstraZeneca.com. Applicants should send a CV, list of publications and the names and addresses of at least two persons that can be approached to obtain further information. Website: http://bioinformatics.nki.nl Closing date: 30 January 2009 L.F.A.Wessels, Ph.D Bioinformatics and Statistics The Netherlands Cancer Institute Plesmanlaan 121, 1066 CX Amsterdam The Netherlands Tel: +31 (0)20 5127987 Fax: +31 (0)20 6691383 Mobile: +31 (0)634485714 http://bioinformatics.nki.nl/ L.F.A.Wessels, Ph.D Bioinformatics and Statistics The Netherlands Cancer Institute Plesmanlaan 121, 1066 CX Amsterdam The Netherlands Tel: +31 (0)20 5127987 Fax: +31 (0)20 6691383 Mobile: +31 (0)634485714 http://bioinformatics.nki.nl/
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
participants (1)
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Lodewyk Wessels