Description du sujet de thèse

Development of a Light-Sheet Microscope for Deep Imaging of the Drosophila melanogaster Brain

Contexte de travail

Detecting multiple molecular species simultaneously—such as DNA, RNA, and proteins—in tissues and whole organisms is essential for understanding complex biological processes, including cell signaling, gene expression, and tissue organization. Recent advances in multiplexed and super-resolution imaging have made it possible to study spatial and molecular interactions with unprecedented resolution, providing crucial insights into processes such as cancer development and embryogenesis.

In our group, we have developed Hi-M, an imaging technique designed to study the three-dimensional organization of chromatin in individual cells. The technical details and analytical protocols of this technology have been published as open-source resources, making it widely accessible to the scientific community.

A major potential application of these techniques lies in the study of pediatric cancers, which often originate during fetal development due to disruptions in gene regulation mechanisms. The Drosophila brain has proven to be a particularly useful model for understanding the mechanisms involved in these rare diseases. However, current imaging technologies face a significant limitation: they cannot be used for 3D imaging of whole tissues or organisms, which complicates the study of complex biological systems.

This PhD project aims to overcome this limitation by developing a high-throughput microscope capable of imaging dozens of molecular species across large volumes. The system will integrate two key technologies: a fluid-handling robotic system and a light-sheet microscope. Both of these technical developments will be based on open-source designs, with all technical details already described in the literature and freely available.

The student's work will focus on three main objectives:
1. Building a prototype of a light-sheet microscope optimized for Hi-M imaging.
2. Developing a Python-based user interface to control the microscope and facilitate experiments.
3. Collaborating with biologists to conduct the first proof-of-concept studies within the Cell-ID project, using Drosophila melanogaster as a model to study pediatric cancer development.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

The project will adopt an open science approach, ensuring that all developments are freely shared without patent restrictions, thus promoting rapid adoption and reuse by the broader scientific community.

This project will enable the study of 3D chromatin structure and transcriptional dynamics during neuronal differentiation in Drosophila. These advancements will not only facilitate the study of cancer models in this organism but also pave the way for applying this approach to other pediatric cancer models.