Bioinformatics Postdoc

POST DOCTORAL BIOINFORMATICIAN IDENTIFICATION AND VALIDATION OF NEW TARGETS FOR COLORECTAL CANCER OVERALL OBJECTIVES The aim of this project is to redefine colorectal cancer (CRC) at the molecular level, by identifying and validating new activated pathways and specific drug targets for defined CRC patient populations. The project will employ the complementary expertise and tools at Astra Zeneca, two academic laboratories (those of Lodewyk Wessels and Rene Bernards at the Netherlands Cancer Institute, Amsterdam) and a leading diagnostics company with an established presence in oncology (Agendia BV, Amsterdam). PROJECT OUTLINE AND STRATEGY We will first use computational approaches to perform a ‘pathway’ or ‘module’ level integration of molecular profiling (gene expression and next generation sequencing data) and extensive clinical annotation data from a collection of 400 CRC tumours to identify and prioritise pathways that are deregulated in each CRC sub-disease. Next, we will define for each pathway, targets that are amenable to drug discovery efforts, and that can be validated in cell culture models. To enable target validation, we will develop approaches to identify, based on molecular profiling data, CRC cell lines in the AZ collection that represent each molecular sub-disease. Once these are in place, target validation experiments will be conducted, using established RNAi methodology. Targets whose functions are shown to be essential for cell viability in the appropriate cell line models will then be recommended for new drug discovery projects. These results will be fed back to refine the target section procedure based on the tumor data. EMPLOYER INFORMATION The Netherlands Cancer Institute is a dedicated cancer center conducting research in all major areas of cancer, with a strong emphasis on translational research. The Bioinformatics and Statistics group (Wessels lab.) provides leadership on the collection and analysis of data for the research programs of the institute, by developing novel compuational approaches and performing state of the art analyses of a wide array of data types, including laboratory and animal experiments, clinical trials, and epidemiologic studies. REQUIREMENTS The ideal candidate is a highly motivated postdoc with a strong background in bioinformatics or computational biology. The vacancy is a research position within the field of bioinformatics/computational biology and the research will be carried out in close collaboration with the involved partners: Bernards lab, Astra Zeneca and Agendia. The ideal candidate has a background in the analysis of high throughput molecular data, computational diagnostics, bioinformatics, computer science, statistics or physics with strong analytical and algorithmic skills. EMPLOYMENT CONDITIONS The temporary employment will be for a period of three years. The gross monthly salary for a Postdoc will range from €3140,- to €3.495,- and depends on previous experience. We can help you find housing. The NKI-AVL has been listed in the top 25 of ‘Best Employers’ in 2009 offering a specialized cancer research institute and hospital with good working conditions and an excellent atmosphere. INTERESTED? Please contact Dr. Lodewyk Wessels, tel. +31 20 512 7987 or e-mail: l.wessels@nki.nl or Dr George Orphanides, Director of Discovery Medicine, tel. +44 1625 232312 or e-mail George.Orphanides@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 1 May 2011

COMPUTATIONAL ANALYSIS OF NEXT GENERATION SEQUENCE DATA THREE BIOINFORMATICS POSITIONS PROJECT OUTLINE Genomic alterations are major determinant of responses to (targeted) therapies in cancer. In fact, the best positive and negative predictors of responses to targeted therapies are alterations in kinases or their direct downstream effectors. To gain insight into resistance mechanisms to therapy and thus better tailor treatment, we are approaching this problem from two different angles. First we have transplanted tumors from mouse models of breast cancer and treated these tumors with a range of (targeted) therapies. Matched pre- and post treatment pairs of resistant and sensitive tumors have been full exon sequenced and are available for analysis. The goal is to detect genomic alterations associated with response to therapy. Second, we have acquired large panels of human tumors, on which we are currently performing kinase exon sequencing. More specifically, we are performing sequencing on 1) 400 samples from the NEO-ALTTO study to find alterations associated with resistance to HER2 targeted therapies; 2) at least 200 colorectal samples and 300 breast cancers (triple negatives and invasive lobular carcinomas) to detect alterations frequently occurring in these patient populations. A very strong feature of all these datasets is that matched controls are available to ensure high accuracy in variant calling. The successful candidates will work closely with the biological groups to develop computational approaches for the detection of mutations and copy number alterations associated with specific cancer subtypes as well as therapy response in human and mouse model-derived tumors. CANDIDATE REQUIREMENTS –EDUCATION AND EXPERIENCE We are seeking highly motivated Postdoc and PhD candidates with a degree in bioinformatics or a mathematical discipline with a strong cancer biological interest. Applicants should either have strong modeling/applied statistics skills or strong documented experience in analyzing high-throughput sequencing data. In addition, we strongly value experience in one or more of the following: sequence analysis, machine learning, applied statistics and R, computer science and expression analysis. The candidate also needs to be proficient in a programming language such as Java, Perl or Python, and be comfortable with Linux systems. Fluency in spoken and written English is a strong requirement. LOCATION The project will employ the complementary expertise and tools of three groups participating in the Cancer Systems Biology Center (csbc.nki.nl) at the Netherlands Cancer Institute, Amsterdam: Rene Bernards (Molecular Carcinogenesis), Jos Jonkers (Mouse Models for Breast Cancer) and Lodewyk Wessels (Computational Biology). The position are primarily embedded within the Bioinformatics and Statistics Group (Wessels) (bioinformatics.nki.nl) at the Netherlands Cancer Institute, Amsterdam. CONTACT DETAILS Please contact Dr. 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 to obtain further information. Also see bioinformatics.nki.nl and csbc.nki.nl for further information. CLOSING DATE: 15 JANUARY 2012

COMPUTATIONAL BIOLOGY POSITION: NGS FOR PERSONALIZED MEDICINE PROJECT OUTLINE Genetic alterations are major determinant of responses to (targeted) therapies in cancer. To gain insight into resistance mechanisms to therapy and thus better tailor treatment, genetic and response characterization for large panels of tumors are required. The Center for Personalized Cancer Treatment (CPCT) is a collaboration between the University Medical Center Utrecht, The Erasmus Medical Center Rotterdam and The Netherlands Cancer Institute Amsterdam, aimed at collecting and characterizing such cohorts. By the end of this year we will have collected and sequenced a total of 1500 tumor and normal samples. The successful candidates will work closely with biologists and clinicians to develop computational approaches that characterize the mutational landscape of these cancers with specific emphasis on the impact this landscape has on therapy response. To this end the candidate will have proprietary access to data from the Sanger Cell line panel (www.cancerRxgene.org). The goal is to integrate this database with the tumor exome and response data to bring personalized medicine a step closed to the clinic. CANDIDATE REQUIREMENTS 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 strong documented experience in analyzing high-throughput sequencing data. In addition, we value experience in one or more of the following: sequence analysis, clinical data analysis, gene expression analysis, machine learning or applied statistics. The candidate needs to be proficient in programming languages such as Java, Perl or Python, and be comfortable with Linux systems. Fluency in spoken and written English is a strong requirement. LOCATION The project will employ the complementary expertise and tools of four groups participating in the Center for Personalized Cancer Treatment: Edwin Cuppen and Emile Voest at the University Medical Center Utrecht and Rene Bernards (Molecular Carcinogenesis) and Lodewyk Wessels (Computational Biology) at the Netherlands Cancer Institute, Amsterdam. The position is primarily embedded within the Bioinformatics and Statistics Group (Wessels) (bioinformatics.nki.nl) at the Netherlands Cancer Institute, Amsterdam. CONTACT DETAILS Please contact Dr. 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 FEBRUARY 2013
participants (1)
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Lodewyk Wessels