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Molecular Networks of Dopaminergic Neurons in Chordates

Objective

Background. Parkinson Disease is the second most common progressive neurodegenerative disorder. The selective degeneration of subsets of midbrain dopaminergic neurons is believed to be the primary cause for disruption of the ability to control movements. Objective. We propose to apply a highly interdisciplinary approach to construct complex networks consisting of protein coding genes, non-protein-coding genes and cis-regulatory elements within dopaminergic neurons in the brain across three chordate organisms (Mouse, Zebrafish and Ciona) to identify and compare gene regulatory networks in these neurons. This will be achieved by: • Expression profiling of genes on single dopaminergic neurons via laser microdissection and transgenic lines in Mouse, Ciona and Zebrafish • HT-Sequencing of microCAGE assays on dopaminergic neurons, providing TSS usage and transcript discovery • Microscopy HTS of cis-regulatory elements • siRNA and morpholino network perturbation experiments • Innovative systems biology approaches to decipher and define molecular networks Data generated by microCAGE and microarray will define a set of key genes in dopaminergic neurons, in which cis-regulatory elements will be predicted and screened utilizing HTS in zebrafish. The data will aid network reconstruction, which will be validated by perturbation experiments. This project relies also on the availability of data produced through the many existing collaborations among consortium partners such as FP6 funded TRANSCODE project as well as the international Fantom3 consortium. Potential impact: The prevalence of PD in Europe today is ~2 million people. Within the next 50 years, the number is expected to rise to 5 million. Thus, the burden placed by dementia on the working-age population will rise dramatically. No treatments are known to slow the progression of the disease. Deciphering the basic networks of dopaminergic neurons will generate novel diagnostic and therapeutic candidates.

Call for proposal

FP7-HEALTH-2007-B
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Coordinator

SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Address
Via Bonomea 265
34136 Trieste
Italy
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 406 400
Administrative Contact
Luca Bardi (Mr.)

Participants (9)

CONSORZIO PER IL CENTRO DI BIOMEDICINA MOLECOLARE SCARL
Italy
EU contribution
€ 357 200
Address
Strada Statale 14 Km 163 5 Basovizza
34149 Trieste
Activity type
Research Organisations
Administrative Contact
Nicola Dorigo Salamon (Mr.)
RIKEN THE INSTITUTE OF PHYSICAL ANDCHEMICAL RESEARCH
Japan
EU contribution
€ 277 400
Address
Hirosawa 2-1
351 0198 Wako Shi Saitama
Activity type
Research Organisations
Administrative Contact
Haruo Yamaguchi (Mr.)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 279 400
Address
Rue Michel Ange 3
75794 Paris
Activity type
Other
Administrative Contact
Beatrice Saint-Cricq (Ms.)
ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Germany
EU contribution
€ 297 400
Address
Fahnenbergplatz
79098 Freiburg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Wolfgang Driever (Prof.)
THE UNIVERSITY OF BIRMINGHAM
United Kingdom
EU contribution
€ 398 400
Address
Edgbaston
B15 2TT Birmingham
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Robert Fekete (Mr.)
KARLSRUHER INSTITUT FUER TECHNOLOGIE
Germany
EU contribution
€ 565 980
Address
Kaiserstrasse 12
76131 Karlsruhe
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Natascha Wallburg (Ms.)
CLINICAL GENE NETWORKS AB

Participation ended

Sweden
EU contribution
€ 69 290,40
Address
Karolinska Sience Park - Fogdevreten 2
171 77 Stockholm
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jesper Tegner (Prof.)
UCL Elizabeth Garrett Anderson Institute for Women’s Health
United Kingdom
EU contribution
€ 230 400
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Greta Borg-Carbott (Ms.)
YH YOUHEALTH AB
Sweden
EU contribution
€ 85 309,60
Address
Fogdevreten 2 Karolinska Science
171 77 Stockholm
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jesper Tegnér (Prof.)