Regulation of Motile Cilia Assembly in Lung Disease

肺部疾病中活动纤毛组装的调节

基本信息

  • 批准号:
    10608147
  • 负责人:
  • 金额:
    $ 78.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-08-17 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Cilia dysfunction leads to chronic lung disease, as occurs in the genetic syndrome primary ciliary dyskinesis (PCD) and may contribute to impaired airway clearance in obstructive pulmonary disease (COPD). Unlike cystic fibrosis, which also causes chronic airway destruction, there is no specific therapy for cilia-related diseases. We now know that most PCD mutations result in defective production, transport, or proper placement of ciliary motors along the ciliary axoneme. However, the exact mechanism by which this occurs is not understood, impeding the development of cilia-specific therapeutic strategies. Thus, our goal is to determine how ciliary motor components are directed from the cytoplasm, into the cilia, then find their way to specific sites along the ciliary axoneme. In this proposal, we trace the passage of the multifunctional, heterodimer CCDC39/CCDC40, which when mutant result in disorganized axonemal microtubule structure and severe PCD disease. CCDC39 trafficking serves to identify the mechanisms by which ciliary components move from the cytoplasm, en route to the basal body, and into cilia by intraflagellar transport (IFT). Our preliminary data indicate that: (1) Ciliary cargoes, including CCDC39, bind centriolar satellite proteins that function as “cars” to facilitate trafficking to the basal body; (2) CCDC39/CCDC40 are linked to microtubules in association with two novel “staple” proteins; and (3) CCDC39 is an IFT co-adaptor protein, with ciliary protein MLF1, for cargo delivery to cilia. We hypothesize that movement of ciliary cargo from the cytoplasm to cilia engages transport mechanisms using satellite proteins, then co-adapter proteins, including CCDC39/CCDC40, to properly assemble cilia. We will characterize this series of pathways in the Specific Aims: (1) Determine how components of motile cilia are trafficked from the cytoplasm to basal bodies; (2) Characterize the multifunctional protein CCDC39 by biophysical and biochemical means that will identify the role of novel staple proteins; and (3) Identify the role for CCDC39 and MLF1 as IFT co-adapter proteins in PCD mutants and COPD tissues. The project uses highly integrated strategies that employ models from single cell organisms to human tissues carried out by the multidisciplinary Washington University Cilia Group, to define new pathways for cilia assembly that can be translated to therapies.
项目总结/文摘

项目成果

期刊论文数量(28)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Centrosome-dependent microtubule modifications set the conditions for axon formation.
  • DOI:
    10.1016/j.celrep.2022.110686
  • 发表时间:
    2022-04-19
  • 期刊:
  • 影响因子:
    8.8
  • 作者:
    Meka, Durga Praveen;Kobler, Oliver;Hong, Shuai;Friedrich, Carina Meta;Wuesthoff, Souhaila;Henis, Melad;Schwanke, Birgit;Krisp, Christoph;Schmuelling, Nessa;Rueter, Rene;Ruecker, Tabitha;Betleja, Ewelina;Cheng, Tao;Mahjoub, Moe R.;Soba, Peter;Schluter, Hartmut;Fornasiero, Eugenio F.;de Anda, Froylan Calderon
  • 通讯作者:
    de Anda, Froylan Calderon
GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program.
  • DOI:
    10.1038/s41419-023-05720-4
  • 发表时间:
    2023-03-17
  • 期刊:
  • 影响因子:
    9
  • 作者:
    Lewis, Michael;Terre, Berta;Knobel, Philip A.;Cheng, Tao;Lu, Hao;Attolini, Camille Stephan-Otto;Smak, Jordann;Coyaud, Etienne;Garcia-Cao, Isabel;Sharma, Shalu;Vineethakumari, Chithran;Querol, Jessica;Gil-Gomez, Gabriel;Piergiovanni, Gabriele;Costanzo, Vincenzo;Peiro, Sandra;Raught, Brian;Zhao, Haotian;Salvatella, Xavier;Roy, Sudipto;Mahjoub, Moe R.;Stracker, Travis H.
  • 通讯作者:
    Stracker, Travis H.
Super-Resolution Microscopy and FIB-SEM Imaging Reveal Parental Centriole-Derived, Hybrid Cilium in Mammalian Multiciliated Cells.
  • DOI:
    10.1016/j.devcel.2020.09.016
  • 发表时间:
    2020-10-26
  • 期刊:
  • 影响因子:
    11.8
  • 作者:
    Liu Z;Nguyen QPH;Nanjundappa R;Delgehyr N;Megherbi A;Doherty R;Thompson J;Jackson C;Albulescu A;Heng YM;Lucas JS;Dell SD;Meunier A;Czymmek K;Mahjoub MR;Mennella V
  • 通讯作者:
    Mennella V
Magnify is a universal molecular anchoring strategy for expansion microscopy.
  • DOI:
    10.1038/s41587-022-01546-1
  • 发表时间:
    2023-06
  • 期刊:
  • 影响因子:
    46.9
  • 作者:
    Klimas, Aleksandra;Gallagher, Brendan R.;Wijesekara, Piyumi;Fekir, Sinda;DiBernardo, Emma F.;Cheng, Zhangyu;Stolz, Donna B.;Cambi, Franca;Watkins, Simon C.;Brody, Steven L.;Horani, Amjad;Barth, Alison L.;Moore, Christopher I.;Ren, Xi;Zhao, Yongxin
  • 通讯作者:
    Zhao, Yongxin
Variations in infection control practices suggest a need for guidelines in primary ciliary dyskinesia patient care.
感染控制实践的变化表明需要制定原发性纤毛运动障碍患者护理指南。
  • DOI:
    10.1002/ppul.25836
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Caliskan,AyseB;Horani,Amjad;Manion,Michele;Brody,StevenL
  • 通讯作者:
    Brody,StevenL
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Steven Brody其他文献

Steven Brody的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Steven Brody', 18)}}的其他基金

Molecular Imaging CCR2 Lung Inflammation and Fibrosis
分子影像 CCR2 肺部炎症和纤维化
  • 批准号:
    10343745
  • 财政年份:
    2021
  • 资助金额:
    $ 78.59万
  • 项目类别:
Molecular Imaging CCR2 Lung Inflammation and Fibrosis
分子影像 CCR2 肺部炎症和纤维化
  • 批准号:
    10543473
  • 财政年份:
    2021
  • 资助金额:
    $ 78.59万
  • 项目类别:
Cellular and Molecular Features of Gene Mutations in Primary Ciliary Dyskinesia
原发性纤毛运动障碍基因突变的细胞和分子特征
  • 批准号:
    9898458
  • 财政年份:
    2019
  • 资助金额:
    $ 78.59万
  • 项目类别:
Cellular and Molecular Features of Gene Mutations in Primary Ciliary Dyskinesia
原发性纤毛运动障碍基因突变的细胞和分子特征
  • 批准号:
    10378548
  • 财政年份:
    2019
  • 资助金额:
    $ 78.59万
  • 项目类别:
PET IMAGING CCR2 IN LUNG INFLAMMATION
肺部炎症中 CCR2 的 PET 成像
  • 批准号:
    9090560
  • 财政年份:
    2016
  • 资助金额:
    $ 78.59万
  • 项目类别:
REGULATION OF MOTILE CILIA ASSEMBLY IN LUNG DISEASE
肺部疾病中活动纤毛组件的调节
  • 批准号:
    8941243
  • 财政年份:
    2015
  • 资助金额:
    $ 78.59万
  • 项目类别:
ROLE OF MYB FOR AIRWAY EPITHELIAL CELL DIFFERENTIATION
MYB 在气道上皮细胞分化中的作用
  • 批准号:
    9268062
  • 财政年份:
    2015
  • 资助金额:
    $ 78.59万
  • 项目类别:
Regulation of Motile Cilia Assembly in Lung Disease
肺部疾病中活动纤毛组装的调节
  • 批准号:
    9887501
  • 财政年份:
    2015
  • 资助金额:
    $ 78.59万
  • 项目类别:
ROLE OF MYB FOR AIRWAY EPITHELIAL CELL DIFFERENTIATION
MYB 在气道上皮细胞分化中的作用
  • 批准号:
    8885389
  • 财政年份:
    2015
  • 资助金额:
    $ 78.59万
  • 项目类别:
Regulation of Motile Cilia Assembly in Lung Disease
肺部疾病中活动纤毛组装的调节
  • 批准号:
    10376783
  • 财政年份:
    2015
  • 资助金额:
    $ 78.59万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了