Job ID: 118108

PhD project: Role of micro-RNAs in the fate determination of neural progenitors during cortex development in the mouse brain

Position: Ph.D. Student

Deadline: 14 April 2024

Employment Start Date: 1 October 2024

Contract Length: 3 years

City: Marseille

Country: France

Institution: Aix Marseille Université

Department: IBDM

Description:

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master’s degree in a non-French university. This project is one of the 13 proposed projects. Not all proposed projects will be funded, check our website for details.

From embryonic stages E11 to E16, neural stem cells in the ventricular zone generate cortical neurons in the mouse brain. These neurons migrate radially to form distinct layers, each with specific functions and connectivity. Between E16 and birth, the same stem cells differentiate into glial cells. Thus, during embryogenesis, a unique pool of neural stem cells generates a wide variety of cell types. Despite extensive studies on gene expression and epigenetics, a comprehensive understanding of the molecular mechanisms governing the establishment of cell diversity in the cortex remains elusive.

Mi-RNAs are small non-coding RNAs that regulate gene expression by interacting with homologous mRNAs. Each mi-RNA can potentially regulate the expression of hundreds of targets, and conversely, a single mRNA is predicted to be targeted by numerous mi-RNAs. Thus, mi-RNAs can act as orchestrators in the development of organs as complex as the mammalian cortex. However, due to the specificity of their structure and mode of action, which makes their analysis experimentally challenging, mi-RNAs are often neglected in genetic screens.

Our team has been studying the role of mi-RNAs in the control of neurogenesis for several years. We have developed a strong expertise in this area. We have also developed several tools to study the expression and function of mi-RNAs in vivo. Recently, a post-doctoral fellow, using sophisticated approaches such as in-utero injection of dyes and FACS sorting, has generated a unique resource of RNA samples extracted from neural stem cells and intermediate progenitors of cortical neurons derived from E11 to E18 injected embryos. The current project aims to analyze these samples to identify mi-RNAs whose expression varies with the embryonic stage. The function of these mi-RNAs in regulating the fate of new neurons will then be investigated. The project will be carried out in several steps:

– Mi-RNAs sequencing of RNA samples using the sequencing machine (mini-Seq, Illumina) that we have recently purchased, using the original protocol set up by Surbhi, a PhD student funded by the NeuroSchool PhD program since 2020.

– These data will be bioinformatically analyzed to identify mi-RNAs differentially expressed between embryonic stages. The nature, the function, and the expression pattern of the predicted targets of these mi-RNAs will also be part of the analysis. Subsequently, we will be able to propose mi-RNA-mRNA interactions potentially determining the fate of cortical progenitor.

– To validate the role of these interactions, gain-of-function and loss-of-function plasmids (mostly for mi-RNAs, but also for mRNAs) will be electroporated in utero at the relevant embryonic stage. The phenotype and localization of the electroporated neurons will be analyzed using fluorescence microscopy.

The candidate must have a strong background in bioinformatics. Solid skills in molecular biology and cytology would be a plus. The candidate must be rigorous, have good communication skills, and be able to work in a team environment.