AXONSURVIVAL

Axon survival: the role of protein synthesis

 Coordinatore THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 2˙426˙572 €
 EC contributo 2˙426˙572 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2012-ADG_20120314
 Funding Scheme ERC-AG
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-03-01   -   2018-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

 Organization address address: The Old Schools, Trinity Lane
city: CAMBRIDGE
postcode: CB2 1TN

contact info
Titolo: Mrs.
Nome: Liesbeth
Cognome: Krul
Email: send email
Telefono: 441223000000
Fax: 441223000000

UK (CAMBRIDGE) hostInstitution 2˙426˙572.80
2    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

 Organization address address: The Old Schools, Trinity Lane
city: CAMBRIDGE
postcode: CB2 1TN

contact info
Titolo: Prof.
Nome: Christine Elizabeth
Cognome: Holt
Email: send email
Telefono: +44 1223 333750
Fax: +44 1223 333840

UK (CAMBRIDGE) hostInstitution 2˙426˙572.80

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

trophic    synthesis    mrnas    ribosomal    local    rps    degeneration    rp    axon    axons    functional    extra    axonal    protein    translation    optic    maintenance   

 Obiettivo del progetto (Objective)

'Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.'

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MICROMECCA (2012)

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LIFEINVERSE (2014)

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