Origins of Cell Geometry
Origins of Cell Geometry
批准号:
10337226
负责人:
Wallace Marshall
金额:
$64.99万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-02-01 至 2024-01-31
关键词:
Abnormal CellAddressAnimal ModelBiological ModelsCell physiologyCellsCellular StructuresCellular biologyComplexDevelopmentDiagnosisDiseaseEngineeringFlagellaGeneticGenomicsGeometryHuman bodyImage AnalysisLearningLengthLifeLinkMethodsMicroscopeModelingMolecular BiologyMorphogenesisNatural regenerationOrganellesOrganismPhysicsPhysiologicalRegulationSeriesShapesStructureSystems AnalysisTestingThinkingTimeWorkbasecancer typecell typeinterdisciplinary approachmathematical modelmicroscopic imagingnanomachinetool
中文摘要
摘要
细胞是高度复杂的活纳米机器,具有非常精确的美丽结构。
这不仅适用于纤毛虫或放射虫等自由生物,
在人体内。这些复杂的结构直接与
细胞的生理功能和细胞几何形状的改变是许多细胞的标志。
疾病状态。然而,在大多数情况下,我们几乎没有关于细胞如何
在细胞器大小和形状的水平上决定它们的几何形状。因此,理解
细胞几何形状的起源仍然是细胞生物学中未解决的基本问题。
挑战的一部分是细胞几何学涉及多个空间尺度,
分子到整个细胞。跨越尺度之间的鸿沟需要我们
超越传统的分子生物学方法,引入物理学方法,
工程.因此,我的建议是基于以下方面的综合结合:
方法,使用几种不同的模式生物和细胞类型来解决
细胞几何形状的起源在几个不同的大小尺度。在单个细胞器的水平上,
我将继续探索鞭毛长度控制的机制,作为一个范例,
细胞器大小调节,重点是使用定量方法来测试一系列
细胞如何感知鞭毛长度的机制模型。在
与此同时,我们将应用我们为实现这一目标而制定的经验教训和方法,
思考鞭毛来研究其他细胞器的大小控制和几何形状,
单独地和组合地。通过同时考虑多个细胞器,
了解如何在更全面级别查看单元格几何形状。在更大的范围内,我们将
继续我们的发展的经典模式生物,Stentor蓝斑,作为一个
用于分析整体细胞形态发生和再生的基因组模型系统。
使用Stentor,我们打算追求两个相关的问题,即细胞如何知道它是
几何结构被扰动,以及它如何指导正确细胞的重新组装,
几何学,这两个问题对所有细胞类型都具有普遍意义,但
特别容易在Stentor学习。我们建议的工作是统一的重点,
只有一个问题--细胞内部的几何结构是从哪里来的。我们将使用不同的
模型系统来解决这个问题的不同方面,但在所有情况下,我们将采取
一种跨学科的方法,结合了遗传学,基因组学,显微镜,
图像分析和数学建模。
英文摘要
Abstract
Cells are highly complex living nanomachines with beautiful structures of great precision.
This is true not only for free living organisms like ciliates or radiolarians, but also for cells
inside the human body. These complicated structures are directly linked to the
physiological functions of cells, and alterations in cell geometry are a hallmark of many
disease states. Yet in most cases we have almost no information about how cells
determine their geometry at the level of organelle size and shape. Thus, understanding
the origins of cell geometry remains a fundamental unsolved problem in cell biology.
Part of the challenge is that cell geometry involves multiple spatial scales ranging from
molecules up to the whole cell. Spanning this gap between scales requires us to go
beyond traditional molecular biology approaches and bring in methods from physics and
engineering. For this reason my proposal is based on an integrated combination of
approaches, using several different model organisms and cell types to address the
origins of cell geometry at several different size scales. At the level of single organelles,
I will continue to probe the mechanism of flagellar length control as a paradigm for
organelle size regulation, with a focus on using quantitative methods to test a series of
mechanistic models for how a cell might be able to sense the length of its flagellum. At
the same time, we will apply the lessons and approaches that we have developed for
thinking about flagella to examine size control and geometry of other cellular organelles,
singly and in combination. By considering multiple organelles at the same time, we can
learn how to view cell geometry at a more integrative level. At a larger scale, we will
continue our development of the classic model organism, Stentor coeruleus, as a
genomic model system for analyzing global cell morphogenesis and regeneration.
Using Stentor, we intend to pursue the two linked questions of how a cell knows that is
geometry has been perturbed, and how it directs the re-assembly of a correct cell
geometry, both questions that have general significance to all cell types but which are
particularly easy to study in Stentor. Our proposed work is unified by the focus on a
single question – where does geometry come from inside a cell. We will use different
model systems to address different aspects of this question, but in all cases we will take
an interdisciplinary approach that combines tools of genetics, genomics, microscopy,
image analysis, and mathematical modeling.
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Origins of Cell Geometry
-
批准号:10090612
-
项目类别:
-
资助金额:$64.99万
-
财政年份:2019
-
负责人:Wallace Marshall
-
依托单位:
Origins of Cell Geometry
-
批准号:10565687
-
项目类别:
-
资助金额:$64.99万
-
财政年份:2019
-
负责人:Wallace Marshall
-
依托单位:
Pattern formation and regeneration in a single cell
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批准号:9206510
-
项目类别:
-
资助金额:$41.37万
-
财政年份:2015
-
负责人:Wallace Marshall
-
依托单位:
CILIA PROTEOME
-
批准号:8365850
-
项目类别:
-
资助金额:$1.28万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:9262238
-
项目类别:
-
资助金额:$30.51万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:8257907
-
项目类别:
-
资助金额:$22.37万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:8912834
-
项目类别:
-
资助金额:$30.5万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:8082509
-
项目类别:
-
资助金额:$22.37万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:9065592
-
项目类别:
-
资助金额:$30.51万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:8464746
-
项目类别:
-
资助金额:$21.59万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Modeling and Analysis of the Flagellar Length Control System
-
批准号:8656713
-
项目类别:
-
资助金额:$22.37万
-
财政年份:2011
-
负责人:Wallace Marshall
-
依托单位:
Analyzing And Engineering Networks That Control Spatial Organization
-
批准号:9339704
-
项目类别:
-
资助金额:$28.82万
-
财政年份:2010
-
负责人:Wallace Marshall
-
依托单位:
Analyzing And Engineering Networks That Control Spatial Organization
-
批准号:9171159
-
项目类别:
-
资助金额:$54.16万
-
财政年份:2010
-
负责人:Wallace Marshall
-
依托单位:
Integrative Program in Complex Biological System (ipCBS)
-
批准号:10178009
-
项目类别:
-
资助金额:$18.45万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
Integrative Program in Complex Biological System (ipCBS)
-
批准号:9340219
-
项目类别:
-
资助金额:$27.59万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
Pattern formation & regeneration in a single cell
-
批准号:8321514
-
项目类别:
-
资助金额:$36.72万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
Integrative Program in Complex Biological System (ipCBS)
-
批准号:10440389
-
项目类别:
-
资助金额:$17.41万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
Pattern formation & regeneration in a single cell
-
批准号:8536838
-
项目类别:
-
资助金额:$35.62万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
Integrative Program in Complex Biological System (ipCBS)
-
批准号:10641344
-
项目类别:
-
资助金额:$9.8万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
Pattern formation & regeneration in a single cell
-
批准号:7946372
-
项目类别:
-
资助金额:$37.09万
-
财政年份:2009
-
负责人:Wallace Marshall
-
依托单位:
海外基金