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Content archived on 2024-06-18

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.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Call for proposal

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FP7-HEALTH-2007-B
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

CP-FP - Small or medium-scale focused research project

Coordinator

SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
EU contribution
€ 406 400,00
Address
VIA BONOMEA 265
34136 Trieste
Italy

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Region
Nord-Est Friuli-Venezia Giulia Trieste
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Participants (9)

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