Project description DEENESFRITPL Understanding the invasive nature of paediatric high-grade brain tumours Diffuse intrinsic pontine glioma (DIPG) is an aggressive childhood cancer of the brain stem. It is a terminal illness with a median overall survival of 9 months. The EU-funded CANCER INVASION project aims to understand the mechanisms driving the invasive growth of DIPG. The researchers will employ state-of-the-art imaging and transcriptomics to investigate murine models of the disease to gain knowledge on the progression of DIPG in the developing brain. The implementation of large-scale single-cell resolution 3D imaging and intravital microscopy will enable imaging of tumour cell behaviour in living mice. The project will provide fundamental knowledge about the invasion mechanisms of cancer cells that govern DIPG spreading and may identify new potential therapeutic targets for this deadly disease. Show the project objective Hide the project objective Objective Introduction: The ability of a cancer cell to invade into the surrounding tissue is the main feature of malignant cancer progression. Diffuse Intrinsic Pontine Glioma (DIPG) is a paediatric high-grade brain tumour with no chance of survival due to its highly invasive nature.Goal: By combining state-of-the-art imaging and transcriptomics, we aim to identify and target the key mechanisms driving the highly invasive growth of DIPG.Technology advances: Two unique single cell resolution imaging techniques that we have recently developed will be implemented: Large-scale Single-cell Resolution 3D imaging (LSR-3D) that allows visualization of complete tumour specimens and intravital microscopy using a cranial imaging window that allows imaging of tumour cell behaviour in living mice. In addition, we will apply a technique of live imaging Patch-seq to perform behaviour studies together with single cell RNA profiling. Expected results: Using a glioma murine model in which the disease is induced in neonates and a new embryonic model based on in utero electroporation, we expect to gain knowledge on the progression of DIPG in maturing brain. LSR-3D imaging on human and murine specimens will provide insight into the cellular tumour composition and its integration in the neuroglial network. With intravital imaging, we will characterize invasive cancer cell behaviour and functional connections with healthy brain cells. In combination with Patch-seq, we will identify transcriptional program(s) specific to invasive behaviour. Altogether, we expect to identify novel key players in cancer invasion and assess their potential to prevent DIPG progression. Future perspective: With the studies proposed, we will gain fundamental insights into the cancer cell invasion mechanisms that govern DIPG which may provide new potential therapeutic target(s) for this dismal disease. Overall, the knowledge and advanced technologies obtained here will be of great value for the tumour biology field. Fields of science natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinepaediatricsnatural sciencesbiological sciencesgeneticsRNAnatural scienceschemical scienceselectrochemistrybioelectrochemistryelectroporation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-STG - ERC Starting Grant Call for proposal ERC-2018-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV Net EU contribution € 1 500 000,00 Address Heidelberglaan 25 3584CS Utrecht Netherlands See on map Region West-Nederland Utrecht Utrecht Activity type Other Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV Netherlands Net EU contribution € 1 500 000,00 Address Heidelberglaan 25 3584CS Utrecht See on map Region West-Nederland Utrecht Utrecht Activity type Other Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
