Job ID: 119709

Post-doc position to study the contribution of spinal interneurons to the etiopathogenesis of Amyotrophic Lateral Sclerosis

Position: Post-doctoral Position

Deadline: 31 August 2024

Employment Start Date: 1 March 2025

Contract Length: 36 months

City: Louvain-la-Neuve

Country: Belgium

Institution: UCLouvain

Department: Louvain Institute of Biomolecular Science and Technology (LIBST), Animal Molecular and Cellular Biology (AMCB) group

Description:

We are looking for a highly motivated post-doctoral researcher in international mobility with a strong background in neurobiology and a consistant academic record to join a team in the lab fully dedicated to the identification of the causal mechanisms of initiation and progression of amyotrophic lateral sclerosis (ALS).

ALS is an adult-onset devastating neurodegenerative disease primarily characterized by the death of upper and of lower motor neurons. However, animal models and in vitro or cell transplant studies demonstrated that non-cell autonomous mechanisms involving astrocytes, oligodendrocytes and interneurons contribute or could even be causative of the disease. Yet, the contribution of spinal interneurons to the pathology remains unsolved. We hypothesize that spinal interneurons are either causal agents or modulators of alterations leading to ALS. Therefore, the goal of this project is to determine the contribution of spinal interneuron populations to the initiation or to the progression of the disease. To address this question, we will first rely on an existing mouse model of ALS wherein a ubiquitously-expressed mutated form of SOD1 can be selectively removed from cell populations of interest, enabling to evaluate the contribution of each spinal interneuron population to the pathology. However, 98% of the ALS patients do not present with SOD1 alterations. In contrast, accumulation of TDP-43 is a hallmark of ALS and is observed in a vast majority of familial or sporadic forms of the disease. Therefore, we are currently generating, using a CrispR/Cas9 genome editing strategy, a new mouse model allowing the conditional production of a mutated form of TDP-43 specifically in spinal neuronal populations. The ability of these populations to induce or to modulate the progression of the ALS symptoms in these two models will be evaluated. These combined studies should enable to determine the contribution of spinal interneurons to the onset or to the progression of ALS, opening a door towards a better understanding and a better treatment of this pathology.

A strong expertise in molecular biology, histology, mouse colony management and motor behaviour analyses is required. Any experience in the field of neurodegenerative disorders will be an asset.