Sizing and Scaling in Functional Muscle Cells
Sizing and Scaling in Functional Muscle Cells
批准号:
10206979
负责人:
MARY K BAYLIES
金额:
$36.46万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-06-01 至 2026-05-31
关键词:
AgingAreaAtrophicBasic ScienceBiologicalCachexiaCell NucleusCell SizeCell fusionCellsCentronuclear myopathyCommunicationCytoplasmic TailDiseaseDrosophila genusExerciseFinancial compensationGenesGeneticGoalsGrowthHuman bodyHypertrophyImageIndividualInvestigationLeadLengthMalignant NeoplasmsMissionMolecularMovementMuscleMuscle CellsMuscle FibersMuscle functionMuscular AtrophyMyopathyNemaline MyopathiesNuclearOrganellesPhysiologicalPloidiesPositioning AttributeProcessRegenerative MedicineRegulationRegulation of Cell SizeResearchRhabdomyosarcomaSignal TransductionSkeletal MuscleWorkin vivoinsightmathematical methodsmathematical modelmechanical forcenovelregional differencerelating to nervous systemresponsesoft tissue
中文摘要
项目摘要/摘要
贝利实验室的使命是提供基础研究成果,以支持更好的治疗方法
一系列肌肉疾病。我们的目标是识别基因和机制,这些基因和机制对于
骨骼肌的形成和健康功能,以及这些机制在疾病状态下出现错误的地方
如肌肉疾病(线状和中心核肌病),肌肉萎缩(恶病质,衰老),以及
软组织癌(横纹肌肉瘤)。具体地说,该实验室的目标是了解导致
骨骼肌:细胞命运承诺、细胞-细胞融合、细胞器的运动和定位,如
细胞核、肌纤维的生长和成熟。这项研究是通过开发和结合
新的遗传学、细胞生物学、成像、分子和数学方法,使用果蝇和
哺乳动物的肌肉细胞。我们目前的调查集中在一个基本问题上:什么决定肌肉
单元格大小?控制细胞大小的机制还知之甚少。对于骨骼动物来说尤其如此
肌肉细胞,可能有数百个细胞核,是人体最大的细胞之一。骨骼
肌肉细胞有一种非凡的能力,可以在运动(肥大)时增加自己的体积,并
因不活动、衰老或疾病(萎缩)而变小。我们对果蝇的研究揭示了关键的核
可由肌肉细胞调节和协调的参数(数量、DNA含量、大小、活动)
以产生特定的大小。我们还发现,肌肉细胞中的许多细胞核在数量上不同,并且
沿着肌肉纤维长度的活动。我们在未来五年的主要问题包括:如何
肌肉细胞会产生这些区域差异,但在全球范围内协调单个细胞内的细胞核吗?
这种差异在其他细胞器中也很明显吗?同样,有哪些具体的信号和机制
沿着肌肉细胞建立和维持核的同一性;每个核对其
局部胞浆区域和整个肌肉细胞?每个核是如何建立其细胞质区域和
是否存在地区差异?最后,在肥大或萎缩的情况下,细胞核和
细胞质的特性和补偿/通讯机制受到了影响?总之,我们的工作将
确定正常、肥大和萎缩条件下肌肉细胞大小的定义参数及其
肌肉功能所需的生理范围。我们的研究将揭示细胞大小调节的一般原理,
洞察这些过程的不当调控如何导致疾病,并告知再生
针对肌肉的药物。
英文摘要
Project Summary/Abstract
The mission of the Baylies lab is to deliver basic research findings that will support better therapies across a
range of muscle diseases. Our goals are the identification of genes and mechanisms that are essential for the
formation and healthy functioning of skeletal muscle, and where these mechanisms go awry in disease states
such as muscular disorders (nemaline and centronuclear myopathies), muscle wasting (cachexia, aging), and
soft tissue cancer (rhabdomyosarcoma). Specifically, the lab aims to understand key processes that lead to
skeletal muscle: cell fate commitment, cell-cell fusion, movement and positioning of organelles such as the
nucleus, and muscle fiber growth and maturation. That research is conducted by developing and combining
novel genetic, cell biological, imaging, molecular and mathematical approaches, using Drosophila and
mammalian muscle cells. Our current investigations focus on a fundamental question: what determines muscle
cell size? The mechanisms that control cell size are poorly understood. This is particularly true for a skeletal
muscle cell, which may have hundreds of nuclei and is among the largest cells in the human body. Skeletal
muscle cells have a remarkable capacity to increase their size in response to exercise (hypertrophy), and to
decrease in size upon inactivity, aging, or disease (atrophy). Our work in Drosophila has revealed critical nuclear
parameters (number, DNA content, size, activity) that can each be adjusted and coordinated by the muscle cell
to generate a particular size. We have also found that the many nuclei in a muscle cell vary in number and
activity along the length of a muscle fiber. Key questions we are pursuing over the next five years include: How
does a muscle cell generates these regional differences yet globally coordinate the nuclei within a single cell?
Are such differences apparent in other organelles? Similarly, what are the specific signals and mechanisms that
establish and maintain nuclear identity along the muscle cell; what are the contributions of each nucleus to their
local cytoplasmic domain and to the entire muscle cell? How does each nucleus set up its cytoplasmic area and
are there regional differences? Finally, under conditions of hypertrophy or atrophy, how are nuclear and
cytoplasmic identities and the compensation/communication mechanisms impacted? Altogether, our work will
identify defining parameters of muscle cell size under normal, hypertrophic and atrophic conditions, and their
physiological range required for muscle function. Our studies will reveal general principles of cell size regulation,
provide insight to how improper regulation of these processes results in disease, and inform regenerative
medicine aimed at muscle.
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会议论文
Sizing and Scaling in Functional Muscle Cells
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批准号:10582054
-
项目类别:
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资助金额:$8.73万
-
财政年份:2021
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负责人:MARY K BAYLIES
-
依托单位:
Sizing and Scaling in Functional Muscle Cells
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批准号:10625969
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项目类别:
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资助金额:$44.02万
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财政年份:2021
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负责人:MARY K BAYLIES
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依托单位:
Sizing and Scaling in Functional Muscle Cells
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批准号:10391520
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项目类别:
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资助金额:$44.02万
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财政年份:2021
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负责人:MARY K BAYLIES
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依托单位:
Sizing and Scaling in Functional Muscle Cells
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批准号:9389959
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资助金额:$45.93万
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财政年份:2017
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负责人:MARY K BAYLIES
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依托单位:
Sizing and Scaling in Functional Muscle Cells
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批准号:9753015
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项目类别:
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资助金额:$45.94万
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财政年份:2017
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负责人:MARY K BAYLIES
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依托单位:
Therapeutic target discovery in Drosophila models of Nemaline Myopathy
-
批准号:9001905
-
项目类别:
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资助金额:$23.22万
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财政年份:2015
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负责人:MARY K BAYLIES
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依托单位:
Mechanisms and Function of Myonuclear Positioning
-
批准号:10557796
-
项目类别:
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资助金额:$60.82万
-
财政年份:2014
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负责人:MARY K BAYLIES
-
依托单位:
Mechanisms and Function of Myonuclear Positioning
-
批准号:10361441
-
项目类别:
-
资助金额:$65.18万
-
财政年份:2014
-
负责人:MARY K BAYLIES
-
依托单位:
Mechanisms and Function of Myonuclear Positioning
-
批准号:9302676
-
项目类别:
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资助金额:$41.8万
-
财政年份:2014
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负责人:MARY K BAYLIES
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依托单位:
Mechanisms and Function of Myonuclear Positioning
-
批准号:8760508
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项目类别:
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资助金额:$40.75万
-
财政年份:2014
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负责人:MARY K BAYLIES
-
依托单位:
Mechanisms and Function of Myonuclear Positioning
-
批准号:8915054
-
项目类别:
-
资助金额:$40.31万
-
财政年份:2014
-
负责人:MARY K BAYLIES
-
依托单位:
Development, Function and Repair of the Muscle Cell
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批准号:8319075
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项目类别:
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资助金额:$2.0万
-
财政年份:2012
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负责人:MARY K BAYLIES
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依托单位:
Mechanisms Regulating Myoblast Fusion in Drosophila
-
批准号:7838301
-
项目类别:
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资助金额:$53.2万
-
财政年份:2009
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负责人:MARY K BAYLIES
-
依托单位:
Mechanisms Regulating Myoblast Fusion in Drosophila
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批准号:7468357
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项目类别:
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资助金额:$36.1万
-
财政年份:2007
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负责人:MARY K BAYLIES
-
依托单位:
Mechanisms Regulating Myoblast Fusion in Drosophila
-
批准号:7904252
-
项目类别:
-
资助金额:$35.74万
-
财政年份:2007
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负责人:MARY K BAYLIES
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依托单位:
Mechanisms Regulating Myoblast Fusion in Drosophila
-
批准号:7667741
-
项目类别:
-
资助金额:$36.1万
-
财政年份:2007
-
负责人:MARY K BAYLIES
-
依托单位:
Mechanisms Regulating Myoblast Fusion in Drosophila
-
批准号:7317373
-
项目类别:
-
资助金额:$36.1万
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财政年份:2007
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负责人:MARY K BAYLIES
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依托单位:
Cell Fate Determination in the Mesoderm of Drosophila
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批准号:7033839
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项目类别:
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资助金额:$35.96万
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财政年份:1999
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负责人:MARY K BAYLIES
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依托单位:
CELL FATE DETERMINATION IN THE MESODERM OF DROSOPHILA
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批准号:6627217
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项目类别:
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资助金额:$31.98万
-
财政年份:1999
-
负责人:MARY K BAYLIES
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依托单位:
Cell Fate Determination in the Mesoderm of Drosophila
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批准号:7210626
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项目类别:
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资助金额:$38.09万
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财政年份:1999
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负责人:MARY K BAYLIES
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