Modulating the UPR to treat Parkinson’s disease

Parkinson’s Disease (PD) is a devastating neurodegenerative disease, which affects a growing number of patients in Europe. The lack of treatment for patients, who rapidly become disabled, brings high social and economic burdens for families and society. Despite numerous studies on PD, scientific research is still behind in term of strategies to halt disease progression. In our project, we will explore novel and promising protective mechanisms to reduce the pathological hallmarks in models of PD. We have recently shown that mild Endoplasmic Reticulum (ER) stress (ER preconditioning), by tunicamycin™ treatment, induces the unfolded protein response (UPR), which results in neuronal protection in cellular and animal models of PD (Fouillet et al, 2012). In four specific tasks, we propose a unique approach at the whole organism (Drosophila) and cellular levels (human neuroblastoma cells) to understand the underlying mechanisms of tunicamycin-mediated protection in PD. We will establish the contribution of xbp-1-independent protection that is mediated by Ire1 in models of PD (Drosophila PD models as well as human cell lines). We will use the Drosophila a-Synuclein (a-Syn) model and test if the protection mediated by Tm is dependent on Ire1 and/or xbp1. We will also study the role of specific Regulated Ire1-dependent decay (RIDD) targets in Tm-mediated neuroprotection and test directly the role of these RIDD targets in Tm mediated protection. This is a unique approach to precisely identify the mechanisms by which ER stress protects from neurodegeneration in PD models. The long-term objective of this project is to open therapeutic perspectives for PD patients.

The CNRS ANR program will cover the salary for two years.

About the Institute: The École Normale Supérieure (ENS) is well known in France and has a solid international reputation among leading scientific institutions, making it a top choice for graduate students and post-docs. The ENS is also a nationally renowned teaching Institution. With its very competitive national entry exam, the ENS Lyon selects outstanding undergraduate and graduate students.

The applicant will enjoy the growing fly/arthropod community at ENS with 7 groups in total.

About the city: Located in the center of Europe, Lyon is the second French biggest city, 2 hours south of Paris by TGV (fast train), 2 hours from Italy or Switzerland and 3 hours from Spain.

: http://www.en.lyon-france.com/

http://www.lyon-photos.com/diaporama/index_fetelumieres2006_43.htm

Experience in genetics or neurodegeneration is preferred.

Send CV with cover letter and 3 letters of reference to bertrand.mollereau(at)ens-lon.fr

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