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
• 负责人: Karyn A Esser
• 金额: $ 34.91万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10746522
• 关键词: Acute; Administrative Supplement; Biological Specimen Banks; Biomedical Research; Biotin; Blood; COVID-19 pandemic; Cell Nucleus; Colon; Companions; Coupled; Data; Data Analyses; Data Set; Development; Disease; Enzymes; Epigenetic Process; Exercise; Funding; Gene Expression; Genetic Transcription; Genomics; Goals; Health; Human; In Vitro; Kidney; Label; Liver; Lung; Manuscripts; Maps; Methodology; Methods; Modeling; Molecular; Muscle; Nuclear; Paper; Pathway interactions; Peripheral; Phase; Physical activity; Plasmids; Postdoctoral Fellow; Prevention; Proteins; Proteome; Proteomics; Publications; RNA Processing; Rattus; Regulation; Resources; Sampling; Site; Skeletal Muscle; Streptavidin; Testing; Tissues; Transducers; Writing; animal facility; chromatin remodeling; design; exercise training; experience; experimental study; in vivo; insight; mRNA Expression; novel; pandemic disease; release factor; response; tool; transcription factor; transcriptome sequencing; transcriptomics

Summary Given the importance of physical activity in healthy living and prevention and treatment of many diseases, it is not surprising that determining the molecular mechanisms or “map” of the exercise response has become an important focus of biomedical research. The Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC) is a multicenter consortium that is currently being designed to achieve this important goal. The UF PASS Phase 2 experiments have been focused on two goals. The first has been to develop the use of a new method to support the discovery of factors released from muscle during exercise. The tool is the TurboID enzyme that can label proteins in close proximity with a biotin moiety. With this labeling we can selectively extract proteins derived from skeletal muscle with streptavidin beads from other peripheral tissues and blood. The second goal of our Phase 2 experiments is focused on direct determination of transcription factors within the nucleus following acute exercise to support the known changes in gene expression. To approach this challenge, we have optimized isolation of nuclei from tissue, starting with muscle tissue. We have identified enriched clusters of proteins that are associated with transcription, RNA processing and chromatin remodeling that provide insight in the muscle changes. For this supplement, we would like to take these studies to publication with inclusion of additional tissues such as liver, kidney and colon. We have proposed the following three specific aims with associated manuscripts: Specific Aim 1. To develop the TurboID methodology for discover of proteins released from muscle at 4 and 24hrs following an acute bout of exercise. Manuscript 1 Specific Aim 2. To define the nuclear proteome changes with acute exercise in liver, lung and muscle at immediate post exercise and 1hr post exercise. Identify novel pathways discovered with this approach, map targeted transcription factor changes coupled with gene expression with deep RNA sequencing. Manuscript 2 Specific Aim 3. To write, at least one other manuscript using MoTrPAC PASS data already available. One plan is to focus on the acute transcriptional response to exercise data in muscle, and other tissues to define common and unique genomic and transcriptomic responses.

总结 鉴于体育活动对健康生活和预防及治疗多种疾病的重要性， 确定运动反应的分子机制或“图谱”， 成为生物医学研究的一个重要领域。身体活动的分子传感器 人类联盟（MoTrPAC）是一个多中心联盟，目前正在设计实现 这一重要目标。 UF PASS第2阶段实验集中在两个目标上。第一个是发展 使用一种新的方法来支持发现运动过程中肌肉释放的因子。该工具 TurboID酶可以标记与生物素部分非常接近的蛋白质。有了这个标签， 可以选择性地提取来自骨骼肌的蛋白质， 组织和血液。我们第二阶段实验的第二个目标是直接测定 急性运动后细胞核内的转录因子，以支持已知的基因变化， 表情为了应对这一挑战，我们优化了从组织中分离细胞核的方法， 肌肉组织我们已经鉴定了与转录相关的富集蛋白质簇， RNA加工和染色质重塑提供了肌肉变化的见解。为此 作为补充，我们希望将这些研究纳入其他组织，如 肝脏肾脏和结肠 我们提出了以下三个具体目标和相关手稿： 具体目标1。开发TurboID方法，用于发现肌肉在4 ℃时释放的蛋白质 以及剧烈运动后24小时。曼尼托角1 具体目标2。目的：研究急性运动对大鼠肝、肺和肌肉细胞核蛋白质组的影响。 运动后立即和运动后1小时。识别用这种方法发现的新途径， 利用深度RNA测序绘制靶向转录因子变化以及基因表达。 Mandarin pt 2 具体目标3。要写，至少有一个其他手稿使用MoTrPAC PASS数据已经可用。 一个计划是关注肌肉和其他组织对运动数据的急性转录反应， 定义共同和独特的基因组和转录组反应。

项目成果

Reinventing the wheel: comparison of two wheel cage styles for assessing mouse voluntary running activity.

重新发明轮子：比较两种轮笼样式以评估小鼠自愿跑步活动。

• DOI: 10.1152/japplphysiol.00880.2017
• 发表时间: 2018
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Seward,T;Harfmann,BD;Esser,KA;Schroder,EA
• 通讯作者: Schroder,EA

Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function.

靶向大脑特异性 tau 蛋白病会损害周围骨骼肌的完整性和功能。

• DOI: 10.1101/2023.11.17.567586
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Alava,Bryan;Hery,Gabriela;Sidhom,Silvana;Prokop,Stefan;Esser,Karyn;Abisambra,Jose
• 通讯作者: Abisambra,Jose

Optimization of the Omni-ATAC protocol to chromatin accessibility profiling in snap-frozen rat adipose and muscle tissues.

• DOI: 10.1016/j.mex.2022.101681
• 发表时间: 2022
• 期刊: METHODSX
• 影响因子: 1.9
• 作者: Nair, Venugopalan D.;Vasoya, Mital;Nair, Vishnu;Smith, Gregory R.;Pincas, Hanna;Ge, Yongchao;Douglas, Collin M.;Esser, Karyn A.;Sealfon, Stuart C.
• 通讯作者: Sealfon, Stuart C.

Exercise Timing and Circadian Rhythms.

• DOI: 10.1016/j.cophys.2019.04.020
• 发表时间: 2019-08
• 期刊: Current opinion in physiology
• 影响因子: 2.5
• 作者: C. Wolff;K. Esser

A Role for Exercise to Counter Skeletal Muscle Clock Disruption.

• DOI: 10.1249/jes.0000000000000235
• 发表时间: 2021-01
• 期刊: Exercise and sport sciences reviews
• 影响因子: 5.7
• 作者: Erickson ML;Esser KA;Kraus WE;Buford TW;Redman LM
• 通讯作者: Redman LM