H2020Индивидуална стипендия2020–2022

ResolvCiliaTip · Resolving the mechanism of ciliary tip factors in primary and motile cilia assembly and function

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-06-01 → 2022-05-31
Финансиране от ЕС: 145 356 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите за изграждане на цилиите – микроскопични структури, които действат като антени или движат течности в белите дробове – са в центъра на анализа. Разбирането им помага да се обяснят причините за различни генетични заболявания, наречени цилиопатии, които засягат много органи.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Resolving the mechanism of ciliary tip factors in primary and motile cilia assembly and function

The Action “Resolving the mechanism of ciliary tip factors in primary and motile cilia assembly and function” aims to find out how some of our cells build non-motile cilium, a tiny single projection on their surfaces to catch the signals from the environment like an antenna (photoreceptors in eyes). Another goal is to find out how other cells build motile cilium, which can propel that cell (sperm cell) or how do they build multiple motile cilia that move fluid around them (and in that way clear mucus from the lungs or move the egg to the uterus). This is medically important because the absence of cilia or the errors in their construction and content can cause a wide range of human diseases, collectively called ciliopathies, and they can affect up to 1 in 2000 people. These diseases can affect human development and multiple organs and systems in our bodies. They are caused by mutations in specific genes. Although many genetic causes of ciliopathies are known, a not-so-small proportion of ciliopathy cases remains without a genetic diagnosis. Sometimes even if the mutations in genes that cause ciliopathies are known, it is not clear how the protein products of those genes build cilia or control their functions. The basic structure of both non-motile and motile cilia is very similar, as they contain the main central cytoskeletal scaffold and membrane around it. How this cytoskeletal scaffold is built and maintained is still not completely understood, and yet, the defects in its assembly and organization are the major causes of ciliopathies. Objectives of this Marie Skłodowska Curie Action (MSCA) have been to resolve: (1) how the proteins that cause ciliopathies build the ciliary scaffold and how this affects the function of both non-motile and motile cilia; (2) how they control the overall stability of that ciliary scaffold and the very tip of cilia; and (3) to identify the protein content of non-motile and motile ciliary scaffold and find the potential new causes shared between primary and motile ciliopathies. Another important goal of the MSCA Individual Fellowship is to foster the development of this individual researcher. The fellow and the researchers in the host laboratory resolved the localization and function of ciliopathy-related protein in detail in both non-motile and motile cilia, as well as synergistic action with other important proteins for cilia formation and function.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Cilia are conserved microtubule-based organelles, which extend from the cell surface and have diverse motility and sensory functions, integrating developmentally important signalling pathways. As such, defects in ciliary assembly and/or function can lead to developmental disorders and multi-systemic genetic diseases, termed ciliopathies. The ciliary tip, a region between microtubule ends and the ciliary membrane, is implicated in cilium assembly, disassembly, signalling, and motility. Few ciliary tip proteins identified so far are mutated in ciliopathies. Yet the complete identity of microtubule associated proteins at the ciliary tip of both primary and motile cilia, and the mechanisms underlying their regulation of ciliary microtubule dynamics and geometry, remain unknown. The proposed research will resolve the link between the ciliary tip geometry and function both in primary and motile cilia, as well as molecular mechanisms controlling the microtubule end dynamics at the ciliary tip and identify the full repertoire of ciliary tip components. The research will focus on functional characterization and interactions of the CCDC66 protein, which mutations cause progressive retinal degeneration, the most frequently observed phenotype across different ciliopathies. The CCDC66 is a recently identified tip component of the primary cilia and preliminary experiments suggest the axonemal and ciliary tip localization of CCDC66 in motile cilia. Therefore, we will investigate both the localization and function of CCDC66 at the primary and motile cilia tip with the nanometre-scale precision. We will elucidate the effect of CCDC66 on microtubule end dynamics using the biochemical assays and resolve the molecular proximity map of the CCDC66 using BioID method and proteomics. The results of this project, predicted to better characterize the causative genes of ciliopathies, could make positive impact on clinical studies and enhance diagnostic approaches in future.

Оригинален текст от CORDIS (на английски).

Участници

KOC UNIVERSITY · IstanbulКоординаторТурция