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NEUROMET SIGNED

Shaping of axonal complexity by a dynamic regulation of local metabolic pathways in the developing cortex

Total Cost €

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EC-Contrib. €

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Partnership

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Project "NEUROMET" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE LYON 1 CLAUDE BERNARD 

Organization address
address: BOULEVARD DU 11 NOVEMBRE 1918 NUM43
city: VILLEURBANNE CEDEX
postcode: 69622
website: www.univ-Iyon1.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙300˙000 €
 EC max contribution 1˙300˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-08-01   to  2021-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE LYON 1 CLAUDE BERNARD FR (VILLEURBANNE CEDEX) coordinator 1˙300˙000.00

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 Project objective

The proper function of neuronal circuits in the adult brain relies heavily on glucose metabolism to ensure energy-demanding neuronal functions such as synaptic activity or long distance axonal transport. Deregulation of the energetic metabolism is strongly associated to many neurodegenerative diseases and has been linked to some neuropsychiatric diseases such as schizophrenia. However our current understanding of metabolic regulation in the developing brain and in particular in rapidly growing neurons is still fragmental. I recently identified a novel function for the kinase LKB1 in the control of axon outgrowth and terminal branching in the mouse cortex (Courchet et al. Cell 2013). This novel function of LKB1 involves the kinase NUAK1/ARK5, a poorly studied kinase related to the metabolic regulator AMPK. Furthermore our work uncovered a completely novel mechanism by which LKB1 and NUAK1 control terminal axon branching through the capture of mitochondria at nascent presynaptic sites. However the roles of presynaptic mitochondria in developing neurons and how they contribute to axon morphogenesis remain an open question. In this project I will to study how the regulation of glucose metabolism and mitochondria function by LKB1 and NUAK1 underlie neuron development and circuit formation in the neocortex. We will develop techniques combining live imaging of fluorescent metabolic reporters, functional metabolomics and in vivo manipulation of gene expression in mouse models to identify the relationship between glucose metabolism and axon development. My experimental plan will revolve around three independent aims that will tackle this question from a subcellular scale to circuits in vivo. Overall, this project will provide new insights into the molecular mechanisms underlying the development of the neocortex and will point out some of the consequences of metabolic imbalance on the development of the brain, a question that has many important implications for public health.

 Publications

year authors and title journal last update
List of publications.
2018 Virginie Courchet, Amanda J. Roberts, Géraldine Meyer-Dilhet, Peggy Del Carmine, Tommy L. Lewis, Franck Polleux, Julien Courchet
Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06584-5
Nature Communications 9/1 2019-04-18

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