CCBE1 AND LYMPHATICS

"Functional and genetical characterization of Ccbe1, a novel regulator of lymphangiogenesis"

Coordinatore	KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW    more  Organization address address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS city: AMSTERDAM postcode: 1011 JV contact info Nome: Don Cognome: Van Velzen Email: send email Telefono: +31 30 2121 800 Fax: +31 30 2121 865
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	161˙248 €
EC contributo	161˙248 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2009-IEF
Funding Scheme	MC-IEF
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-03-01   -   2012-02-29

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW  Organization address address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS city: AMSTERDAM postcode: 1011 JV contact info Nome: Don Cognome: Van Velzen Email: send email Telefono: +31 30 2121 800 Fax: +31 30 2121 865	NL (AMSTERDAM)	coordinator	161˙248.80

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 Obiettivo del progetto (Objective)

'Ccbe1 has recently been identified as an essential regulator of lymphangiogenesis in zebrafish. Loss of function of this secreted factor leads to a failure of lymphangioblast budding and a complete lack of lymphatics. Intriguingly, mutations in human CCBE1 are causative for a congenital lymphatic malformation disease, termed Hennekam syndrome (HS). The main goal of this project is to understand the function of Ccbe1 in development and disease. Firstly, since the mode of action of Ccbe1 is completely unknown, we will focus on identifying interaction partners for this secreted protein by three different approaches: (1) I will test the interactions between Ccbe1 and one potential binding partner identified in a yeast-two-hybrid assay (2) I will perform IP experiments with myc-tagged Ccbe1 protein, followed by Mass Spectrometry for protein identification. (3) I will analyze an additional gene causing HS, identified in the human clinic. For all three approaches, candidate genes will be validated further through expression pattern analysis in zebrafish and mouse, in conjunction with functional tests through morpholino injections and co-IP studies with Ccbe1 in zebrafish. Secondly, I will focus on analyzing Ccbe1 conditional mouse knock out models. Using inducible and constitutive tissue specific Cre-recombinase lines, I will identify those tissues and cell types which require Ccbe1 activity for their normal physiological functioning. Particular attention will be on the role of Ccbe1 in those organ systems that are affected in HS patients, i.e. the lymphatic system and the brain. Furthermore, the inducible knockout of Ccbe1 in adult mice will answer the key question whether Ccbe1 is also required during adult stages for lymphangiogenesis. CCBE1 is one of very few genes known to be essential for lymphatic function. The proposed project will help to better understand the mode of action of this recently identified, critical factor in human lymphangiogenesis.'