Comparative analysis of PCP signaling architecture
PCP信令架构对比分析
基本信息
- 批准号:8792538
- 负责人:
- 金额:$ 32.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-06 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAccountingAddressAffectApicalArchitectureBindingBiologicalCellsCharacteristicsComplexConflict (Psychology)Congenital Heart DefectsDefectDevelopmentDiagnosticDiseaseDrosophila genusEpidermisEpithelialEpitheliumEyeGenesGoalsHairHybridsIndividualLegMethodsModelingNeoplasm MetastasisNeural Tube DefectsOutputPathogenesisPathway interactionsPatternPhysiologicalPolycystic Kidney DiseasesPulmonary HypertensionRelative (related person)Research PersonnelSeriesSignal TransductionSignaling MoleculeSpecific qualifier valueStructureSystemTechniquesTherapeuticTissuesWingWorkcancer cellcomparativedeafnessdesignflymathematical methodsmathematical modelmigrationnetwork architecturenovelplanar cell polaritypolarized cellresearch studytool
项目摘要
DESCRIPTION (provided by applicant): The Planar Cell Polarity (PCP) system polarizes cells in some epithelial sheets along an axis orthogonal to their apical-basal axis, and is necessary for numerous physiological functions. Studies in the fruit fly, Drosophila, have led to the concept of a modular system controlling PCP. The PCP genes can be grouped together into functional modules, each representing a genetically and biochemically related unit. However, conflicting models describing the relationships between the principal ("global," "core" and "effector") PCP modules have been proposed, suggesting either a series or parallel relationship upstream of the various tissue specific effector modules. Notably, the connectivity between the PCP modules, and between the PCP modules and their targets is controversial. Targets of PCP signaling may be discrete systems that act within single cells to build polarized structures, or may be multicellular units that themselves constitute modules in which signals within and between cells contribute to patterning. The components of the PCP signaling system, and the effector systems with which they interact, function together to produce emergent patterns. Manipulation of individual PCP signaling molecules in specified groups of cells not only perturbs the polarization of the targeted cells at a subcellular level, but also perturbs patterns of polarity at the multicellular level, often affecting nearby cells in characteristic ways. These kinds of experiments should, in principle, allow us to infer the architecture of the governing control systems, but the relationships between molecular interactions and tissue-level pattern are sufficiently complex that they defy intuitive understanding. Mathematical modeling has been an important tool to address this problem. Here, we propose to combine novel, hybrid models, amenable to analysis, with biological experimentation to better understand the PCP signaling network architecture and whether a single or multiple architectures function in different contexts. Specifically, we propose to first probe the global and core modules and network architecture in two tissues, wing and abdomen, in which the output is hair polarization, but in which mutually exclusive model architectures have been proposed. Next, we will probe the corresponding modules and network architecture in a third system, the bristles, in which the effector is a more complex multicellular system that may be more divergent in how it responds to PCP input. We believe that this work will result in an enhanced understanding of PCP, which will be important in understanding the many vertebrate developmental defects and diseases to which PCP contributes. The work will also produce broadly applicable mathematical tools as well as mathematical model components that can be integrated with existing developmental models.
描述(由申请人提供):平面细胞极性(PCP)系统使一些上皮层中的细胞沿与其顶基轴正交的轴沿着极化,并且是许多生理功能所必需的。对果蝇(Drosophila)的研究产生了控制PCP的模块化系统的概念。五氯苯酚基因可以组合成功能模块,每个模块代表一个遗传和生化相关单位。然而,已经提出了描述主要(“全局”、“核心”和“效应器”)PCP模块之间的关系的冲突模型,表明各种组织特异性效应器模块上游的串联或并联关系。值得注意的是,PCP模块之间以及PCP模块与其目标之间的连接性存在争议。PCP信号传导的目标可能是在单细胞内起作用以构建极化结构的离散系统,或者可能是本身构成模块的多细胞单位,其中细胞内和细胞间的信号有助于图案化。PCP信号系统的组成部分,以及与它们相互作用的效应器系统,共同发挥作用,产生紧急模式。在特定细胞群中操纵单个PCP信号分子不仅在亚细胞水平上扰乱靶细胞的极化,而且在多细胞水平上扰乱极性模式,通常以特征性方式影响附近细胞。原则上,这类实验可以让我们推断出支配控制系统的结构,但分子相互作用和组织水平模式之间的关系非常复杂,无法直观理解。数学建模是解决这一问题的重要工具。在这里,我们建议结合联合收割机新的,混合模型,服从分析,与生物实验,以更好地了解PCP信号网络架构,以及是否一个或多个架构在不同的情况下的功能。具体来说,我们建议首先探测两个组织,翅膀和腹部,其中输出是头发极化,但其中互斥的模型架构已被提出的全球和核心模块和网络架构。接下来,我们将探索第三个系统(鬃毛)中的相应模块和网络架构,其中效应器是一个更复杂的多细胞系统,其对PCP输入的响应方式可能更加不同。我们相信,这项工作将有助于加深对五氯苯酚的了解,这对于了解五氯苯酚导致的许多脊椎动物发育缺陷和疾病至关重要。这项工作还将产生广泛适用的数学工具以及可以与现有发展模型相结合的数学模型组件。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Jeffrey D. Axelrod其他文献
Distinct developmental roles of planar cell polarity proteins vangl1, prickle1, and prickle2 in cortical crescents and primary cilia
- DOI:
10.1016/j.ydbio.2009.05.375 - 发表时间:
2009-07-15 - 期刊:
- 影响因子:
- 作者:
Dragana Antic;Kaye Suyama;Jeffrey D. Axelrod;Matthew P. Scott - 通讯作者:
Matthew P. Scott
Strabismus comes into focus
斜视进入焦点
- DOI:
10.1038/ncb0102-e6 - 发表时间:
2002-01-01 - 期刊:
- 影响因子:19.100
- 作者:
Jeffrey D. Axelrod - 通讯作者:
Jeffrey D. Axelrod
Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling.
- DOI:
- 发表时间:
2001 - 期刊:
- 影响因子:10.5
- 作者:
Jeffrey D. Axelrod - 通讯作者:
Jeffrey D. Axelrod
Molecular mechanism of core planar cell polarity complex function elucidated with single-molecule methods
- DOI:
10.1016/j.bpj.2022.11.526 - 发表时间:
2023-02-10 - 期刊:
- 影响因子:
- 作者:
Silas Boye Nissen;Alexis T. Weiner;Alexander R. Dunn;Jeffrey D. Axelrod - 通讯作者:
Jeffrey D. Axelrod
Biology by numbers: mathematical modelling in developmental biology
按数字分类的生物学:发育生物学中的数学建模
- DOI:
10.1038/nrg2098 - 发表时间:
2007-05-01 - 期刊:
- 影响因子:52.000
- 作者:
Claire J. Tomlin;Jeffrey D. Axelrod - 通讯作者:
Jeffrey D. Axelrod
Jeffrey D. Axelrod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('Jeffrey D. Axelrod', 18)}}的其他基金
Planar cell polarity mechanisms and systems architecture
平面细胞极性机制和系统架构
- 批准号:
10250480 - 财政年份:2019
- 资助金额:
$ 32.88万 - 项目类别:
Planar cell polarity mechanisms and systems architecture
平面细胞极性机制和系统架构
- 批准号:
10018920 - 财政年份:2019
- 资助金额:
$ 32.88万 - 项目类别:
Comparative analysis of PCP signaling architecture
PCP信令架构对比分析
- 批准号:
8607574 - 财政年份:2012
- 资助金额:
$ 32.88万 - 项目类别:
Comparative analysis of PCP signaling architecture
PCP信令架构对比分析
- 批准号:
8245217 - 财政年份:2012
- 资助金额:
$ 32.88万 - 项目类别:
Comparative analysis of PCP signaling architecture
PCP信令架构对比分析
- 批准号:
8417654 - 财政年份:2012
- 资助金额:
$ 32.88万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 32.88万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 32.88万 - 项目类别: