COMPUTATIONAL BIOLOGIST - TUMOR IMMUNOLOGY

VACANCY COMPUTATIONAL BIOLOGIST - TUMOR IMMUNOLOGY YOUR ROLE WITHIN THE INSTITUTE The research groups of Dr Karin de Visser, dr Marleen Kok and Prof dr Lodewyk Wessels, are looking for a motivated and talented Computational Biologist to join their teams at the Netherlands Cancer Institute (NKI). The Inflammation and Cancer group of dr. Karin de Visser is studying the impact of the immune system on metastatic breast cancer utilizing sophisticated mouse tumor models and state-of-the art ex vivo and in vitro immunological and molecular assays. The lab of de Visser closely collaborates with the translational research group of medical oncologist dr Marleen Kok. The mission of this team is to discover novel mechanisms underlying the crosstalk between breast cancer and the immune system, to optimize immunotherapy for breast cancer patients using novel combination treatments in clinical trials and the discovery of predictive biomarkers. The Computational cancer biology group of Prof dr Lodewyk Wessels is focused on quantifying and understanding treatment response in model systems and patients. To this end we develop bespoke and novel computational methods focusing on data integration and tailored to new technologies. We actively collaborate with many research groups in the NKI and strongly believe in the power of 'team science'. PROJECTS You will be involved in the following projects: 1. MOUSE MODELS FOR METASTATIC ESCAPE FROM IMMUNE CONTROL. To study the causal relationship between immune cells and metastatic breast cancer, we utilize state-of-the art genetically engineered mouse tumor models. We have extensive RNA-sequencing datasets of isolated immune cell populations, as well as RNA-sequencing and exome sequencing data of primary breast tumors and organ-specific metastases from these mouse models. You will be responsible for the computational analyses of the data, and to extract candidate pathways/genes from these datasets that can subsequently be tested in follow up experiments in the lab. Moreover, you will link these pre-clinical data to human datasets. 2. SYSTEMIC AND INTRA-TUMORAL IMMUNOMONITORING FOR PRECISION IMMUNE-MODULATION. We are performing extensive immunomonitoring studies in human breast cancer patients treated with immune checkpoint blockade, with the ultimate aim to validate hypotheses derived from our preclinical research in human cancer patients, and to stratify breast cancer patients for immunomodulatory therapies. We are setting-up multiplex immunohistochemistry with antibody panels that audit intratumoral lymphoid and myeloid cell populations and their functional state. In parallel, we have established an extensive multiplex flow cytometry pipeline to monitor the systemic immune landscape of breast cancer patients and healthy controls. These analyses generate a substantial amount of data which require thorough computational analyses. 3. MAPPING IMMUNO-GENOMIC INTERACTIONS. We are interested in dissecting the impact of the genetic make-up of breast tumors on the intra-tumoral and systemic immune landscape. You will be responsible for the identification and validation of genotype-immunophenotype associations by connecting DNA exome sequencing data, RNA sequencing data and immune profiles derived from our mouse tumor models and cancer patients. You will use both publicly available datasets and newly generated datasets. You will be embedded in the collaborative and enthusiastic international research groups of dr. Karin de Visser, dr Marleen Kok and Prof. dr. Lodewyk Wessels, providing a unique environment that combines computational cancer biology with pre-clinical and translational research into immune-oncology. YOUR PROFILE We seek to recruit an ambitious postdoc, capable of independent thinking, with a strong commitment to translational research. Candidates should hold a degree in bioinformatics, computer science or a related discipline, have experience in statistics and/or machine learning and be proficient in bioinformatics programming languages (e.g. R, Python). We expect candidates to be highly self-motivated, creative, and a team-player with strong communication skills. General background knowledge in biology and immunology is essential, and experience with projects involving the use of genomics and immune profiling data to identifying candidate targets and biomarkers is a plus. WANT MORE INFORMATION? Please visit our home pages https://www.nki.nl/divisions/tumor-biology-immunology/de-visser-k-group/ https://ccb.nki.nl or contact Karin de Visser: k.d.visser@nki.nl Marleen Kok: m.kok@nki.nl Lodewyk Wessels: l.wessels@nki.nl

COMPUTATIONAL TUMOR IMMUNOLOGIST: SINGLE CELLS TO CLINICAL RESPONSE The research groups of Dr Marleen Kok, Pia Kvistborg and Lodewyk Wessels, are looking for a motivated and talented Computational Biologist to join their teams at the Netherlands Cancer Institute (NKI). THE PROJECTS With your expertise in computational life sciences and a very good understanding of onco-immunology, you will be involved in the following projects: Single T cell analyses: To study the state of T cells we are investigating tumor-specific T cell responses on the population level as well as on the single cell level using transcriptome analysis and high dimensional (30 parameter) flow cytometry. Using these data, we want to understand how T cell populations differ in their gene expression and functional state depending on their antigen specificity and their place in the immunodominance hierarchy. Clinical systems Immunology: Using exome, TCR sequencing data, whole transcriptome and immunohistochemistry/immunofluorescence data of the tumor microenvironment as well comprehensive flow cytometry data of peripheral blood, we aim to better understand how immune checkpoint blockade - alone or in combination with chemotherapy - affects the breast tumor microenvironment. In parallel, systemic immune response characteristics will be studied. You will be a key player in a translational research team with clinicians and immunologists. YOUR PROFILE You are an ambitious, creative computational biologist, with a strong commitment to translational research. Candidates should hold a degree in bioinformatics, computer science or a related discipline, have experience in statistics and/or machine learning and be proficient in bioinformatics programming languages (e.g. R, Python). We expect candidates to be team-players with strong communication skills. General background knowledge in biology and immunology is essential, and experience with projects involving the use of genomics and immune profiling data to identifying candidate targets and biomarkers is a plus. THE RESEARCH GROUPS You will join the dynamic, international research groups of Pia Kvistborg, Marleen kok and Lodewyk Wessels . You will collaborate with scientists and clinicians with expertise in different disciplines. The translational breast cancer immunology group of Dr Marleen Kok focuses on dissecting breast cancer-immune interactions, to optimize immunotherapy for breast cancer patients using novel combination treatments in clinical trials and the discovery of predictive biomarkers. The T cell immunology group of Dr Pia Kvistborg focuses on understanding the state of tumor-specific T cells in cancer. We are currently investigating two aspects of the tumor-specific T cell response: 1) does the T cell state depend on which type of antigen the T cell is specific for (e.g. tumor-associated vs tumor-specific); and 2) what is the role of immunodominance in the development of the tumor-specific T cell response. The Computational cancer biology group of Prof dr Lodewyk Wessels is focused on quantifying and understanding treatment response in model systems and patients. To this end we develop bespoke and novel computational methods focusing on data integration and tailored to new technologies. We actively collaborate with many research groups in the NKI and strongly believe in the power of ‘team science’. WANT MORE INFORMATION? For further information please visit our home pages Kvistborg group: https://www.nki.nl/divisions/molecular-oncology-immunology/kvistborg-p/ Computational Cancer Biology: ccb.nki.nl or contact Pia Kvistborg, p.kvistborg@nki.nl or Marleen Kok, m.kok@nki.nl, or Lodewyk Wessels, l.wessels@nki.nl

PhD/POSTDOC POSITION: ‘CellCircuits: Mining a genomics compendium to identify therapeutic targets’ CONSORTIUM PARTNERS: Wessels Laboratory, The Netherlands Cancer Institute (NKI), Amsterdam. Brummelkamp Laboratory, The Netherlands Cancer Institute (NKI), Amsterdam. Scenic Biotech BV, Amsterdam, The Netherlands PROJECT DESCRIPTION: Human cells perform highly complex tasks and are equipped with the required machinery and decision-making processes that largely remain poorly understood. Although human genes play a central role, no wiring diagram exists depicting their function. This project will link the function of all human genes to a compendium of cellular processes. This will suggest new entry points to manipulate cellular processes and therapeutic strategies to rebalance disease. PUBLIC-PRIVATE, MULTI-DISCIPLINARY COLLABORATION: This consortium will draw upon 1) Phenosaurus, a large collection (~130) of haploid screens generated in collaboration with Scenic Biotech BV employing the Cell-seq technology developed by the Brummelkamp laboratory; 2) the screening, cell and molecular biology expertise of the Brummelkamp laboratory and the computational know-how of the Wessels laboratory. With the Cell-seq technology proven to be highly effective, the opportunity exists now to cover diverse cellular functions and to use advanced computational network inference approaches to deduce the underlying genetic control mechanisms. EMBEDDING: The successful candidate will be employed in the Wessels and Brummelkamp groups at the Netherlands Cancer Institute, and will regularly liaise with Scenic Biotech to generate sufficient cohesion and momentum. CANDIDATE PROFILE: We are seeking a highly motivated PhD candidate with: • A degree in bioinformatics, computer science or a related discipline • Experience in statistics, machine learning and/or pattern recognition • Proficiency in bioinformatics programming languages (e.g. R, Python) • Good cross-disciplinary collaborative and communication skills • Experience in analysing high-throughput molecular data is a plus • Experience in cancer biology and clinical applications is a plus INTERESTED? Please send a CV and motivation letter to Lodewyk Wessels (l.wessels@nki.nl). Please include the names and contact information of at least two references. WANT MORE INFORMATION? Visit our websites: Wessels lab: Computational Cancer Biology: ccb.nki.nl <http://ccb.nki.nl/> Brummelkamp lab: https://www.nki.nl/divisions/biochemistry/brummelkamp-t-group/ <https://www.nki.nl/divisions/biochemistry/brummelkamp-t-group/> or contact Lodewyk Wessels, l.wessels@nki.nl <mailto:l.wessels@nki.nl> DEADLINE: 1 October 2019 RELEVANT LITERATURE: van de Haar J, Canisius S, Yu MK, Voest EE, Wessels LFA, Ideker T. Identifying Epistasis in Cancer Genomes: A Delicate Affair. Cell. 2019 May 30;177(6):1375-1383. Aben N, Westerhuis JA, Song Y, Kiers HAL, Michaut M, Smilde AK, Wessels LFA. iTOP: inferring the topology of omics data. Bioinformatics. 2018 Sep 1;34(17):i988-i996. Brockmann, M., Blomen, V.A., Nieuwenhuis, J., Stickel, E., Raaben, M., Bleijerveld, O.B., Altelaar, A.F.M., Jae, L.T. 1 and Brummelkamp, T.R1. (2017) Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling. Nature 546, 307-311. Nieuwenhuis, J., Adamopoulos, A., Bleijerveld, O.B., Mazouzi, A., Stickel, E., Celie, P., Altelaar, M., Knipscheer, P., Perrakis, A., Blomen, V.A., and Brummelkamp, T.R. (2017) Vasohibins encode tubulin detyrosinating activity. Science 6369, 1453-1456. Mezzadra, R. 1, Sun, C. 1, Jae, L.T. 1, Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M.E.W., Slagter, M., Rozeman, E.A., Hofland, I., Broek,s A., Horlings, H.M., Wessels, L.F.A., Blank, C.U., Xiao,
participants (1)
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Lodewyk Wessels