The laboratory “Genetics and Biology of Pediatric Tumors” directed by Olivier Delattre at the Curie Institute develops several research programs to understand the biology and oncogenic transformation mechanisms of various pediatric tumors. We are particularly interested in the mechanisms that govern cellular plasticity in childhood cancers and their role in treatment resistance. The Curie Institute provides an excellent scientific environment for high quality research with state-of-the-art equipment as well as a constellation of seminars covering many research areas.
The successful applicant joining the neuroblastoma team will work on a research project funded by INCa and led by Isabelle Janoueix-Lerosey, in collaboration with the laboratory of Valentina Boeva (ETH Zürich), a world-class expert in computational epigenetics in cancer.
Tumor cell plasticity has now been identified as a source of intra-tumor heterogeneity that may contribute to treatment failure in several types of cancer. To further explore the mechanisms of plasticity and their link with epigenetic remodeling, we will focus on neuroblastoma, a tumor of the sympathetic nervous system, derived from multipotent neural crest cells (NCC), which accounts for around 15% of children cancer-related deaths. High-Risk neuroblastoma most often initially responds to intensive chemotherapy; however, relapses frequently occur followed by fatal outcome. Through the analysis of the super-enhancer landscape, we recently revealed two types of cell identity in neuroblastoma: a sympathetic noradrenergic identity and a NCC-like identity, driven by a module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs) and a module containing AP-1 TF, respectively (Boeva et al, Nature Genetics, 2017). We showed that NCC-like cells display mesenchymal features and are less sensitive to chemotherapy. Recent evidence indicates that some neuroblastoma cells exhibit plasticity and are able to shift between an NCC-like/mesenchymal and a noradrenergic identity and vice versa.
This offer provides an opportunity to work on a multifaceted biological problem by developing and applying methods for integrative high-throughput data analysis. Your aim would be to investigate neuroblastoma cell identity, plasticity and heterogeneity using bioinformatics and computational biology approaches, in particular through the analysis of cancer cell ChIP-seq and RNA-seq data, both at the bulk and single cell level. The whole project will contribute to a better characterization of the role of cellular reprogramming in tumorigenesis and will eventually help choice of treatment of neuroblastoma patients.
We are looking for a candidate highly motivated to work with big data, particularly with single cell transcriptomic data and dig into cancer epigenetics. A master’s degree, experience in bioinformatics analysis (in R), and proficiency in English are required. Programming skills (Perl/Python), computational and mathematical background and/or experience in cellular and molecular biology would be a plus.
The position (2 years) is available starting September 1, 2019 or latter. Please apply by sending your CV and publication list together with a motivation letter and the names of two references to:
firstname.lastname@example.org and Valentina.Boeva@inserm.fr. Please indicate “Engineer position application U830” in the subject of your email.