ZFISHSLEEP

Resolving the Neuropharmacology and Genetics of Zebrafish Sleep

 Coordinatore UNIVERSITY COLLEGE LONDON 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 1˙902˙750 €
 EC contributo 1˙902˙750 €
 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-2011-StG_20101109
 Funding Scheme ERC-SG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-02-01   -   2017-01-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Dr.
Nome: Jason
Cognome: Rihel
Email: send email
Telefono: 442077000000
Fax: 442077000000

UK (LONDON) hostInstitution 1˙902˙750.00
2    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Ms.
Nome: Greta
Cognome: Borg-Carbott
Email: send email
Telefono: 442031000000
Fax: 442078000000

UK (LONDON) hostInstitution 1˙902˙750.00

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 Word cloud

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genetics    extend    mutants    mechanisms    regulating    regulate    assays    neurons    brain    small    neural    observe    hcrt    zebrafish    sleep    genetic    behavioural    compounds    wake    conserved   

 Obiettivo del progetto (Objective)

'Sleep is a fundamental process, yet the genetic and neural mechanisms that regulate sleep are largely unknown. We have developed the zebrafish as a model system to study the regulation of sleep because it combines the genetics of invertebrates with the basic brain structures that regulate sleep in humans. We previously designed high throughput behavioural assays to measure sleep behaviours in the fish and used genetic tools to demonstrate that the wake-regulating hypocretin/orexin (Hcrt) system is functionally conserved in the zebrafish. We have also used our assays to perform a small molecule screen and identified both conserved and novel candidate regulators of sleep in zebrafish.

In Aim 1, we will observe the behaviour of wild type and Hcrt receptor mutants to a panel of small molecules known to alter zebrafish sleep. This aim tests the hypothesis that these compounds exert their effects on sleep and wake through the Hcrt system. In Aim 2, we will follow-up on the compounds that had differential effects in the mutants. We will monitor the activity of Hcrt neurons in response to drugs using a new neuroluminescent technique to observe the activity of neurons in freely behaving zebrafish larvae. This Aim will extend the behavioural data to the level of neural circuits. In Aim 3, we will use new methods to globally observe neuronal activity in the zebrafish brain to extend our analysis to neurons thought to interact with the Hcrt system. By observing activity across the sleep/wake cycle, we may also uncover novel sleep regulating neurons.

Overall, this project takes a multidisciplinary approach to the study of sleep and the Hcrt system, leveraging new methods from chemical biology, molecular genetics, and behavioural neuroscience in the zebrafish. As little is known about the mechanisms and sites of action for most sleep-altering compounds, any progress would advance the sleep field and could have clinical relevance to the treatment of sleep disorders.'

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