Descripción del proyecto
Organización de los ápices ciliares en la señalización de Hedgehog
Las células eucariotas están llenas de finas protuberancias llamadas orgánulos ciliados, los cuales tienen funciones esenciales de motilidad, sensoriales y de señalización. La estructura de los cilios es importante para su función, pero no se conocen al detalle los mecanismos subyacentes a la relación entre estructura y función. El proyecto CiliaryTip, financiado con fondos europeos, se propone abordar el papel de la estructura de los cilios en la señalización de Hedgehog, una de las principales vías de señalización basadas en cilios, esencial para el desarrollo embrionario y que interviene en enfermedades. Este trabajo influirá en la forma en la que se analizarán en el futuro las enfermedades relacionadas con la señalización de Hedgehog, al generar información con implicaciones más amplias en relación con el papel sensorial y de señalización de los cilios.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
1678 Nicosia
Chipre