Mots-Clés
high-resolution imaging
cellular interactions
paediatric brain cancers
Description
About Cell-ID
The Cell-ID program focuses on uncovering the molecular mechanisms that govern cell fate determination during neural development and how their disruption contributes to childhood brain cancers.
Our goal is to design strategies for a cell-based interceptive medicine: targeting the earliest cellular and molecular events in cancer to prevent disease progression.
Led by CNRS and Inserm, in collaboration with major French institutions and international partners, Cell-ID integrates omics technologies, advanced imaging, and computational modeling to study genome function and 3D nuclear organization in neural tissues under normal and pathological conditions. By combining cutting-edge experimental tools with predictive models, the program aims to define and modulate cell trajectories during neural development.
About this project
4D investigation of cellular interaction in a Drosophila model of ATRT brain tumours
Pauline Spéder and Christophe Zimmer
Atypical Teratoid Rhabdoid Tumours (ATRT) are highly aggressive pediatric brain tumours primarily driven by the loss of the chromatin remodeling factor SMARCB1. However, the role of the surrounding microenvironment in tumour progression remains poorly understood. To address this, we take advantage of a Drosophila model in which inactivation of snr1 —the fly homolog of SMARCB1— during development induces ATRT-like tumours. This model offers distinct advantages, including well-defined cells of origin, characterized developmental programs, and advanced genetic engineering.
Our research will focus on deciphering the interactions between tumour cells and the host tissue, including neurons, glial cells, and the blood-brain barrier. We will examine host cell responses at multiple levels —structural organisation, cellular processes, gene expression, epigenetic modifications and metabolic changes— to uncover how these factors influence tumour progression.
To achieve this, we require high-resolution, multi-colour imaging techniques to map intricate 3D spatial relationships between host and tumour cells throughout tumour progression. To overcome current technical limitations, our two laboratories are collaborating to develop, refine, and validate a novel imaging system combining hyperspectral imaging with light-sheet illumination. This approach will enable rapid, high-resolution imaging of thick tissue samples with minimal preparation, supporting the detection of four or more fluorescent markers simultaneously.
This cutting-edge imaging platform will allow us to precisely map the dynamics of cellular interactions between host and tumour cells, with the aim to improve our understanding of ATRT biology.