Description du sujet de thèse

The development of the brain implies the correct proliferation, differentiation and migration of neuronal and glial cells of dozens of types. It also imply the correct wiring of the connectome, i.e. the establishment in the mouse of thousands of synapses across 10^8 neuron in a stochastic yet reliable and reproducible way. To study this process we are using the development of the Median Nucleus of the Trapezoid Body (MNTB) in mice, a nucleus of a few thousand cells that invert signal coming from the Cochlear Nucleus (CN) linked to the ear on one side toward the contra-lateral auditory nuclei. Through innovative labeling, imaging and analysis of mouse brain on the one hand and modeling and simulations on the other we are studying quantitatively the development of that circuit aiming for a mechanistic, integrated understanding in health and diseases. This work is the focus of the ANR grant ConnExp, between Anatole Chessel at the LOB and Jean Livet from Institut de la Vision.
This PhD project is focused on working on the data analysis part of that program. Mouse brain with axons from the CN to the MNTB labeled with stochastic color with Brainbow will be imaged using large scale ChroMS microscopy. Starting from the 100s of Gb to Tb volumes, we will trace hundreds of single axons (Fig 2.) and analyze the resulting arbors and curves to extract quantitative characteristics of the MNTB across its development. Preliminary semi-automated tracing workflows and analysis pipeline have been setup that will need to be adapted and augmented [3,4]. Further work include contributing to modeling the connection establishment process and linking intelligently data and models.

Contexte de travail

This PhD will be supervised by Anatole Chessel and is part of a long running interdisciplinary collaboration between biologist, physicist and computational scientist, between Laboratoire Optique et Bioscience at Ecole polytechnique near Paris and Jean Livet's team at Institut de la Vision in Paris; it is funded from an ANR grant involving those two partners. On top of weekly meetings between the student and the supervisor, regular meeting with collaborators, in the context of the ANR grant, will be organized as needed. It will benefit from LOB IT resources in compute and storage, with the possibility of accessing more as needed with local and national resources.

Contraintes et risques

NA