Where: INSERM UMR1441 (Dir. Pr. Pierre Gressens).
The lab research is focused on brain developmental disorders and benefits from powerful interactions with clinicians (child neurologists, fetopathologists, geneticists).
When: two years, starting from May-July 2022.
Job description:
We are looking for a fellow strongly motivated to study the molecular mechanisms linking cellular metabolic pathways and human neocortical growth. More specifically, our project is integrated in an ERANET Neuron collaborative project aiming to enlarge our knowledge on the pathomechanisms involved in primary non-syndromic microcephalies (MCPH), with special focus on crosstalk between microcephaly genes, energetic cellular pathways, vasculogenesis and epigenetic regulation. On our side, we principally take advantage of neocortical organoids induced from human iPS cells to study the impact of the metabolic microenvironment on transitions of progenitors during early stages of neocorticogenesis and on the subsequent extent of neurogenesis.
Main tasks:
- Production of organoids mimicking early stages of neocortical neurogenesis
- Assessment of the influence of cellular metabolic pathways (hypoxia, glutaminolysis) and of mutations of MCPH1 on the fate of neuroprogenitors and on organoid development. Mutations combined to GFP insertion will be introduced in hiPS cells by using CRISPR-Cas9 strategies.
- Expression analysis of relevant molecular markers by immunofluorescence, QPCR and Western blots
- Analysis of neuroprogenitor cell cycle by FACS
- Imaging by conventional and two-photon confocal microscopy.
Skills required
PhD preferentially with a background in neurodevelopment and molecular biology. Valuable experience in cell culture and imaging are highly appreciated as well. Candidate should be highly organized, able to work independently and as part of a team.
Salary
Around 2200€/month, will be funded by ANR (the French National Research Agency) via the ERA-NET Neuron program and be adjusted according to the applicant previous experience and INSERM compliance.