Centre National de la Recherche Scientifique (CNRS)
The Centre National de la Recherche Scientifique (CNRS, The French National Center for Scientific Research) is a government-funded research organization under the administrative authority of French Ministry of Research. The Paris-Saclay Institute of Neuroscience (Neuro-PSI) is a joint Research Unit between the CNRS, beneficiary of the BIND project, and Paris-Saclay University (UMR9197). Neuro-PSI is dedicated to basic Neuroscience, at all scales of analysis, from molecule to cognition and from embryo to adult. It is composed of 3 departments and 24 teams working on the development and evolution of the nervous system, the organization and function of neuronal networks, the neural bases of behaviours and cognitive functions and the mechanisms involved in neuropathologies. Neuro-PSI forms, with the brain imaging Institute NeuroSpin (CEA Saclay), the NeuroSaclay Center promoting Neuroscience at the highest international standards. Neuro-PSI (18000m2) provides technical support and access to state-of-the-art technologies, platforms and facilities for mouse transgenic production and maintenance, behaviour, multi-scale microscopy, histology, cell culture, molecular biology, biochemistry, electrophysiology, brain surgery, optogenetics, vectorology and bioinformatics.
The CNRS partner team has a renowned leadership in deciphering the mechanisms of brain plasticity underlying cognitive processes and how they go awry in rodent models of neurodevelopmental (intellectual disability, Duchenne muscular dystrophy, autism) and neurodegenerative diseases (Alzheimer). The team has a long-standing expertise and know-how in multidisciplinary studies, from molecular to cellular and behavioural levels, designed to characterize pathophysiological mechanisms in transgenic mouse models. This group has a long history in pioneer studies of the neurobehavioral deficits in mouse models of DMD lacking distinct brain dystrophins and in the development of brain gene therapies to alleviate these deficits. A long-lasting collaboration with the group of Aurélie Goyenvalle (U1179-UVSQ-Inserm) already enabled successful demonstration that at least some of the brain dysfunctions due to dystrophin loss can be rescued postnatally by gene therapy (several joint publications, past and ongoing co-direction of PhD students), thus providing a strong basis for the present project.
Partner CNRS leads the WP3 dedicated to the behavioural phenotyping of dystrophic mouse models lacking different brain dystrophins. The aim of this WP is to undertake a fine-level, integrated and comparative characterization of the cognitive, executive and comorbid behavioural dysfunctions in several DMD mouse models lacking different brain dystrophins. A large panel of behavioural tests will be used and the relevant outcome measures will be used in WP4 to evaluate the efficacy of gene therapies based on dystrophin rescue strategies.
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Team
Dr Cyrille Vaillend
Position in Organisation
CNRS Director of Research (DR2) – Team Leader
Profile and Role in the project
Cyrille Vaillend is a CNRS Director of Research leading the team Cognition, Plasticity and Neuropathologies at Neuro-PSI. He has a long-standing expertise and know-how in multidisciplinary studies in the context of behavioural Neuroscience and brain plasticity. He developed a range of paradigms to identify motor, emotional, social, cognitive and executive dysfunctions as well as their molecular, neuroanatomical and physiological bases. He has a renowned history with pioneer in-depth studies of DMD mouse models which enabled identification of relevant outcome measures that he used to evaluate the efficiency of gene-therapy rescue strategies based on exon-skipping and rAAV vectors. Dr Vaillend will be the lead contact for CNRS and coordinate the WP3 (mouse behaviour) with a high degree of multidisciplinary interaction with WP4 (gene therapy).
Professor Sylvie Granon
Position in Organisation
Professor at the Paris-Saclay University – Team leader
Profile and Role in the project
Sylvie Granon is a tenured professor of Neuroscience at Paris-Saclay University and member of the National University Committee (CNU). She leads the team Neurobiology of decision-making composed of 5 PIs and 2 PhD students. She is a recognized expert in the neural bases of executive functions and social decision-making, with a particular interest in prefrontal cortex functions. Her research aims at understanding the development and neuromodulation of executive processes and the bases of individual variability in cognitive, social and emotional processes, using a variety of behavioural conditions applied to a psychiatric mouse models (ADHD, autism, schizophrenia or stress-related disorders). Pr. Granon will collaborate with C Vaillend in WP3 for the deep behavioural phenotyping of executive dysfunctions and comorbidities (social behaviour) in DMD mouse models.
Amel Saoudi
Position in Organisation
PhD student
Profile and Role in the project
Amel Saoudi is a young and motivated PhD student with a background in biochemistry and Neuroscience. She was highly ranked by our doctoral school “Signaling and Integrated Networks in Biology” (BIOSIGNE) and obtained a fellowship from the French Ministry of Education and Research to join our group at Paris-Saclay University in October 2019, under the co-supervision of Dr Vaillend at CNRS and Dr Goyenvalle at UVSQ. Ms Saoudi is involved in the characterisation of behavioural phenotypes in the mdx52 mouse model (WP3) and in the assessment of exon 51 skipping in the brain of this model (WP4). She is trained in behavioural studies, in vivo brain surgery and molecular biology.
Postdoc to be recruited
Position in Organisation
Postdoctoral Researcher
Profile and Role in the project
The postdoctoral scientist will have a PhD in Neuroscience, a strong experience in mouse behaviour, statistical analyses and neurosurgery and be motivated by multidisciplinary studies. He/she will also have basic knowledge and experience in related fields including molecular therapy, genetics, pharmacology, brain plasticity, neuroanatomy, molecular biology and bioinformatics. Supervised by Dr Vaillend with participation of Pr Granon, he/she will develop for WP3 a range of state-of-the-art and novel behavioural paradigms to compare cognitive, emotional, social and high-order executive functions in DMD mouse models and assess their contribution to DMD comorbidities (social disturbances, attention, impulsivity/compulsivity…). He/she will also undertake rescue experiments with a selection of mouse models and innovative molecular tools (AAV, AONs) (WP4).
