Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Genes for impaired migration in C. elegans

We identified C. elegans homologues of three genes related to the RET signalling pathway: ECE1 homologue NEP1, SGK1 (serum- and glucocorticoid-responsive kinase) and T16A9.4, another NEP gene similar to ECE1. Knockout of nep-1 leads to reduced locomotion, when compared to wild type worms, suggesting a neuronal dysfunction of the ECE1 mutant (Spanier et al., manuscript is in preparation). SGK1 acts downstream of PDK-1.

Loss of SGK-1 in C.elegans results in extended generation time, increased life span, and, in combination with mutations in the Akt/PKB homologs AKT-1 and AKT-2, causes constitutive developmental arrest. The SGK/AKT/PKB complex characterized is a downstream effector of RET/Rai/GDNF signalling. We generated a model that can be used to study the downstream effectors of RET/RAI signaling, and the genes regulated inappropriately in mutations of RET/RAI.

Furthermore, interaction studies have been conducted to identify RET interacting partners using a split-ubiquitin yeast interaction screening system and a human interactor libary.

A semi-automated screening platform was established to screen for candidate genes involved in the RET pathway in high-throughput. This platform uses an automatic worm-sorting device to distribute, analyze and redistribute C. elegans test animals in a microtiter format. Several phenotypic parameters were established that allow the quantitative screening of mutational consequences in factors of the RET/RAI pathway.

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Ralf BAUMEISTER, (Head of Laboratory)
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