Muscle clock and weakness: diversity supplement
肌肉时钟和弱点:多样性补充
基本信息
- 批准号:10414186
- 负责人:
- 金额:$ 3.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-29 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalARNTL geneATAC-seqAdministrative SupplementAgeAgingAntibodiesAttentionBioluminescenceChIP-seqChromatinCircadian RhythmsCoupledDNA BindingDataDoseElementsFemaleFloridaGene ExpressionGenesGeneticGenomicsHealthKnockout MiceLearningLengthLongevityMeasuresMedicineMentorsMicroscopyMissionMolecularMolecular TargetMuscleMuscle WeaknessMuscle functionOutcomeOutputPhenotypePhysiologicalPopulation HeterogeneityPropertyProteinsRNA SplicingRegulationResearchResolutionRodent ModelRoleSarcomeresScientistSeriesSkeletal MuscleStructureStudentsTechniquesTestingThick FilamentTissuesTrainingTraining ActivityUnited States National Institutes of HealthUniversitiesWorkadeno-associated viral vectorbone imagingcareercareer developmentcircadian pacemakercollegeconfocal imagingdoctoral studentepigenomicsexperienceexperimental studyfallsfunctional outcomesgraduate studenthuman subjectimaging approachimprovedinterestmalemetabolomicsmouse modelmuscle strengthmuscular structureparent grantparent projectpre-clinicalresearch and developmentresponseskillstranscriptome sequencingtranscriptomics
项目摘要
Abstract: The purpose of this project is to provide research and career development training for Silvana
Sidhom, a current PhD student at the University of Florida. This administrative supplement in response to PA-
21-071: “Research Supplements to Promote Diversity in Health-Related Research (Admin Supp)” will facilitate
career development for the candidate and as well as contribute to the mission of the parent project – to define
molecular targets downstream of the circadian clock that modulate muscle structure with implications for
strength.
The primary objectives of Ms. Sidhom’s proposed research will be to work on experiments related to Aim 2 of
the parent grant. First, she will learn to use confocal imaging approaches with sarcomeric antibodies to define
changes in the M-line and Z-line structural elements of the sarcomere from the control and muscle specific
Bmal1 KO mice. Second, she will use AAV approaches to restore expression of selected sarcomeric genes,
such as Tcap, to test if that is sufficient to restore structure and muscle force. Ms. Sidhom will work actively
with Collin Douglas, another PhD student working on the parent grant as well as Dr. Christopher Wolff, a
postdoctoral associate on this project. Dr. Esser, the PI of the R01, will be the primary mentor for Ms. Sidhom
within the College of Medicine at the University of Florida. We have established her committee and this
includes: Drs. Russ Hepple, Christiaan Leeuwenburgh and Richard Dunn. They are enthusiastic about Ms.
Sidhom as a student and provide appropriate expertise in skeletal muscle and imaging approaches. Silvana
has completed her first year of required courses so the committee will work with Ms. Sidhom to outlined a
series of didactic courses, including the skeletal muscle course taught each fall. The committee will also help
guide Silvana with experiential training activities that will equip her with the necessary skills to progress as an
independent scientist and to fulfill the NIH mission to advance the careers of a diverse population of scientists.
The project is directly related to Aim 2 of the parent grant:
Specific Aim 2: To test the clock controlled genes, Rbm20 and/or Tcap, for their roles in sarcomere
structure and muscle function. This aim will use AAV delivery of Tcap and/or Rbm20 in Bmal1 deficient
muscle to test their contribution to sarcomere structure, myofibrillar protein composition and muscle function.
Sarcomere structural elements will be obtained by super-resolution microscopy with deconvolution techniques
with antibodies to define 2D and 3D properties including sarcomere length, thick filament centrality, M-band
and Z line integrity. Deep RNA-sequencing will be performed on the Rbm20 muscles to define splicing
changes. Functional outcomes will include ex vivo measures to test the impact of structural changes on both
passive/stiffness and active/max force and rate of contraction properties.
摘要:本项目的目的是为Silkenstein提供研究和职业发展培训
Sidhom是佛罗里达大学的博士生。这份行政补充文件是对PA-
21-071:“研究补充,以促进健康相关研究的多样性(行政补充)”将促进
候选人的职业发展,以及有助于母项目的使命-定义
生物钟下游的分子靶点调节肌肉结构,
实力
Sidhom女士提议的研究的主要目标将是进行与2010年目标2有关的实验。
家长补助金首先,她将学习使用共聚焦成像方法与肌节抗体,以确定
肌节的M线和Z线结构元件与对照组和肌肉特异性
Bmal 1 KO小鼠。其次,她将使用AAV方法来恢复选定的肌节基因的表达,
例如Tcap,以测试其是否足以恢复结构和肌肉力量。Sidhom女士会积极地
与柯林道格拉斯,另一个博士生工作的家长补助金以及克里斯托弗沃尔夫博士,一个
这个项目的博士后助理R 01的PI Esser博士将成为Sidhom女士的主要导师
在佛罗里达大学的医学院内。我们已经建立了她的委员会,
包括:Russ Hepple,Christiaan Leeuwenburgh和Richard Dunn博士。他们对女士很热情。
Sidhom作为一名学生,并提供骨骼肌和成像方法的适当专业知识。Silvana
已经完成了第一年的必修课程,因此委员会将与Sidhom女士合作,
一系列教学课程,包括每年秋季教授的骨骼肌课程。委员会还将帮助
指导Silencia进行体验式培训活动,使她具备必要的技能,
独立的科学家,并履行国家卫生研究院的使命,以促进科学家的多元化人口的职业生涯。
该项目与母赠款的目标2直接相关:
具体目标2:检测时钟控制基因Rbm 20和/或Tcap在肌节中的作用
结构和肌肉功能。该目的将使用AAV递送Tcap和/或Rbm 20到Bmal 1缺陷型小鼠中。
肌肉,以测试它们对肌节结构、肌原纤维蛋白组成和肌肉功能的贡献。
肌节结构要素将通过超分辨率显微镜与反卷积技术获得
用抗体定义2D和3D特性,包括肌节长度、粗丝中心性、M带
和Z线完整性。将对Rbm 20肌肉进行深度RNA测序,以确定剪接
变化功能结局将包括体外测量,以测试结构变化对两者的影响
被动/刚度和主动/最大力和收缩率特性。
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)
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Karyn A Esser其他文献
Erratum to: Inducible Cre transgenic mouse strain for skeletal muscle-specific gene targeting
- DOI:
10.1186/2044-5040-2-22 - 发表时间:
2012-10-30 - 期刊:
- 影响因子:4.400
- 作者:
John J McCarthy;Ratchakrit Srikuea;Tyler J Kirby;Charlotte A Peterson;Karyn A Esser - 通讯作者:
Karyn A Esser
Karyn A Esser的其他文献
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{{ truncateString('Karyn A Esser', 18)}}的其他基金
Molecular Transducers of Physical Activity Consortium Coordinating Center
体力活动分子传感器联盟协调中心
- 批准号:
10840609 - 财政年份:2017
- 资助金额:
$ 3.73万 - 项目类别:
UF PASS Administrative Supplement: Regulation of exercise transducers
UF PASS 行政补充:运动传感器的监管
- 批准号:
10746522 - 财政年份:2016
- 资助金额:
$ 3.73万 - 项目类别: