Description du projet
Organisation des extrémités ciliaires dans la voie de signalisation hedgehog
Les cellules eucaryotes sont parsemées de fines protubérances appelées cils, qui possèdent des fonctions essentielles en matière de mobilité, de sensations et de signalisation. La structure des cils est importante pour sa fonction; toutefois, les mécanismes qui sous-tendent la relation entre la structure et la fonction ne sont pas bien compris. Le projet CiliaryTip, financé par l’UE, entend aborder le rôle de la structure ciliaire dans la voie de signalisation hedgehog, l’une des principales voies de signalisation basées sur les cils, essentielle pour le développement embryonnaire et impliquée dans la maladie. Ces travaux auront un impact sur la manière dont les maladies liées à la signalisation hedgehog seront étudiées à l’avenir, apportant ainsi des connaissances avec des implications à plus grande échelle sur le rôle sensoriel et de signalisation des cils.
Objectif
Cilia are microtubule-based organelles with essential motile, sensory and signaling functions. The cilium structure is important for its function however the mechanisms underlying the structure-function relationship are not well understood. The proposed study will address the role of the cilium structure in hedgehog signaling, one of the main cilia-based signaling pathways, essential for embryonic development and implicated in disease. In mammals, cilia are required for hedgehog signaling and the localization of signaling proteins at the distal end of cilia, the ciliary tip, is important for pathway activation. Structural defects at the ciliary tip affect the localization of signaling proteins and pathway activation and cause a subset of cases of Joubert Syndrome. We propose an unbiased and comprehensive approach to elucidate how the ciliary tip organization supports the localization and dynamics of hedgehog signaling proteins at this compartment. This work will impact how we address hedgehog related diseases in the future and will generate insights with broader implications with respect to the signaling and sensory roles of cilia. The fellow will conduct this work in the laboratory of Dr. Skourides at the University of Cyprus, a group with a consistent record of high quality publications, including important findings related to cilia. The Fellow’s experience in studying the ciliary tip in motile cilia and the expertise of the host in cellular and developmental biology ensure the successful implementation of the proposed work. The Fellow has demonstrated great potential in becoming an independent scientist by securing funding for her PhD work and receiving the Seal of Excellence on an MSCA-IF submitted in 2018. Through this fellowship the researcher will acquire both the training and experience that will allow her to transition to an independent career focused on the connection between cilium structure and function and its role in vertebrate development.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1678 Nicosia
Chypre