Excellence in Research: Mitochondrial Damage-Associated Molecular Patterns (mtDAMPs) as Immunostimulants
卓越研究:线粒体损伤相关分子模式 (mtDAMP) 作为免疫刺激剂
基本信息
- 批准号:2302101
- 负责人:
- 金额:$ 92.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
This Excellence in Research (EiR) project aspires to enhance STEM research by tackling the central research question, “Why did our immune systems evolve to treat both microbial danger and cellular damage with inflammation?”. Inflammation follows penetrative trauma, in non-sterile settings, when potentially harmful bacteria are present. Similarly, when an organism’s cells/tissues are injured/damaged, perhaps due to non-penetrative trauma, sterile inflammation follows. Despite the very different circumstances, the inflammatory phenomena following these examples of trauma are surprisingly similar. This project will focus on mitochondria, specifically, mitochondrial peptides and nucleic acids, as mediators of sterile inflammation. The mechanisms of sterile inflammation following muscle contraction-induced injury (CII) that will be studied in this project will fulfill a knowledge gap in exercise physiology. The research may offer further insight into the consequences of mitochondria evolving to be endosymbionts as well as immune/ inflammatory implications of CII. Another objective is to fully leverage the project to enhance research capacity. Students and a postdoctoral fellow will be trained and mentored during this project, increasing retention of the next generation of talent in the STEM pipeline. Meanwhile, pursuit of this research will enhance institutional research capacity at a Historically Black College & University (HBCU).Immune systems treat both microbial danger and cellular damage with inflammation. Inflammation follows penetrative trauma in non-sterile settings, when potentially harmful bacteria are present, and inflammation may follow when an organism’s cells/tissues are injured/damaged due to non-penetrative trauma in sterile conditions. Presently, scientists understand that damage-associated molecular patterns emanating from mitochondria (mtDAMPs) are elevated in trauma patients, and that mtDAMPs play a causal role in sterile inflammation. However, the mechanism underlying this increase and its relevance to exercise physiology is unknown. Specific molecular signatures, such as N-formyl peptides (mtFPs), have been implicated, but other possibilities exist, including the pattern of unmethylated cytosine-phosphate-guanine (CpG) DNA repeats in, and circular nature of, mitochondrial DNA. The investigators hypothesize that muscle contraction-induced injury during exercise causes the release of mtDAMPs, which activate innate immunity, leading to sterile inflammation in athletes. In particular, the investigators will measure the levels of mitochondrial proteins and nucleic acids in exercise-induced sterile inflammation. The investigators will also develop cell culture infrastructure to query in vitro interactions of skeletal muscle cells and innate immune cells, such as monocytes and neutrophils. Structural and thermodynamic properties of the human mtDAMP, nicotinamide adenine dinucleotide dehydrogenase subunit 6 (ND6) will be investigated. The investigators will use a variety of methods, such as ELISA to investigate mitochondrial proteins, PCR to investigate mitochondrial nucleic acids, and x-ray crystallography to elucidate the structure of ND6. This research will shed light on similarities between clinical noninfective trauma and the trauma elicited simply by strenuous exercise.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
这个卓越研究(EiR)项目旨在通过解决中心研究问题“为什么我们的免疫系统进化到能够同时治疗微生物危险和炎症引起的细胞损伤?”来加强STEM研究。在非无菌环境中,当存在潜在的有害细菌时,穿透性创伤会导致炎症。类似地,当生物体的细胞/组织受伤/受损时,可能是由于非穿透性创伤,无菌炎症随之而来。尽管情况非常不同,但这些创伤后的炎症现象惊人地相似。该项目将重点关注线粒体,特别是线粒体肽和核酸,作为无菌炎症的介质。本项目将研究肌肉收缩诱导损伤(CII)后无菌性炎症的机制,这将填补运动生理学的知识空白。这项研究可能会进一步深入了解线粒体进化为内共生体的后果以及CII的免疫/炎症影响。另一个目标是充分利用该项目来提高研究能力。学生和博士后研究员将在该项目期间接受培训和指导,增加STEM管道中下一代人才的保留。与此同时,这项研究的追求将提高一个历史悠久的黑人学院大学(HBCU)的机构研究能力。免疫系统既可以治疗微生物的危险,也可以治疗炎症引起的细胞损伤。当存在潜在有害细菌时,在非无菌环境中的穿透性创伤之后会发生炎症,并且当生物体的细胞/组织由于无菌条件下的非穿透性创伤而受伤/受损时,炎症可能会发生。目前,科学家们了解到,来自线粒体(mtDAMP)的损伤相关分子模式在创伤患者中升高,并且mtDAMP在无菌炎症中发挥因果作用。然而,这种增加的机制及其与运动生理学的相关性尚不清楚。特定的分子特征,如N-甲酰肽(mtFP),已被牵连,但其他可能性存在,包括未甲基化的胞嘧啶-磷酸-鸟嘌呤(CpG)DNA重复序列的模式,和环状的性质,线粒体DNA。研究人员假设,运动过程中肌肉收缩引起的损伤会导致mtDAMP的释放,从而激活先天免疫,导致运动员的无菌炎症。特别是,研究人员将测量运动诱导的无菌性炎症中线粒体蛋白质和核酸的水平。研究人员还将开发细胞培养基础设施,以查询骨骼肌细胞和先天免疫细胞(如单核细胞和中性粒细胞)的体外相互作用。本文研究了人线粒体腺苷二磷酸酶亚基6(ND 6)的结构和热力学性质。研究人员将使用多种方法,如ELISA研究线粒体蛋白,PCR研究线粒体核酸,X射线晶体学研究ND 6的结构。这项研究将阐明临床非感染性创伤和单纯剧烈运动引起的创伤之间的相似性。该奖项反映了NSF的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。
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 }}
Chad Markert其他文献
Chad Markert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('Chad Markert', 18)}}的其他基金
TIP: Infusing Laboratory-Bench STEM Into Exercise Physiology Via Integration of Chemistry, Biology, and Biophysics
提示:通过化学、生物学和生物物理学的整合,将实验室台 STEM 融入运动生理学
- 批准号:
1533476 - 财政年份:2015
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
相似国自然基金
Research on Quantum Field Theory without a Lagrangian Description
- 批准号:24ZR1403900
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
Cell Research
- 批准号:31224802
- 批准年份:2012
- 资助金额:24.0 万元
- 项目类别:专项基金项目
Cell Research
- 批准号:31024804
- 批准年份:2010
- 资助金额:24.0 万元
- 项目类别:专项基金项目
Cell Research (细胞研究)
- 批准号:30824808
- 批准年份:2008
- 资助金额:24.0 万元
- 项目类别:专项基金项目
Research on the Rapid Growth Mechanism of KDP Crystal
- 批准号:10774081
- 批准年份:2007
- 资助金额:45.0 万元
- 项目类别:面上项目
相似海外基金
Collaborative Research: Unraveling the phylogenetic and evolutionary patterns of fragmented mitochondrial genomes in parasitic lice
合作研究:揭示寄生虱线粒体基因组片段的系统发育和进化模式
- 批准号:
2328117 - 财政年份:2024
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Collaborative Research: Unraveling the phylogenetic and evolutionary patterns of fragmented mitochondrial genomes in parasitic lice
合作研究:揭示寄生虱线粒体基因组片段的系统发育和进化模式
- 批准号:
2328119 - 财政年份:2024
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Collaborative Research: Unraveling the phylogenetic and evolutionary patterns of fragmented mitochondrial genomes in parasitic lice
合作研究:揭示寄生虱线粒体基因组片段的系统发育和进化模式
- 批准号:
2328118 - 财政年份:2024
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
DMS/NIGMS 1: Collaborative Research: Advanced Ion Channel Modeling and Computational Tools with Application to Voltage-Dependent Anion Channel and Mitochondrial Model Development
DMS/NIGMS 1:合作研究:先进离子通道建模和计算工具,应用于电压依赖性阴离子通道和线粒体模型开发
- 批准号:
2153387 - 财政年份:2022
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Collaborative Research: Defining functions of an essential, conserved protein that uniquely links the mitochondrial matrix with the cytoplasm
合作研究:定义一种重要的、保守的蛋白质的功能,该蛋白质将线粒体基质与细胞质独特地连接起来
- 批准号:
2215728 - 财政年份:2022
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Collaborative Research: Defining functions of an essential, conserved protein that uniquely links the mitochondrial matrix with the cytoplasm
合作研究:定义一种重要的、保守的蛋白质的功能,该蛋白质将线粒体基质与细胞质独特地连接起来
- 批准号:
2215729 - 财政年份:2022
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
DMS/NIGMS 1: Collaborative Research: Advanced Ion Channel Modeling and Computational Tools with Application to Voltage-Dependent Anion Channel and Mitochondrial Model Development
DMS/NIGMS 1:合作研究:先进离子通道建模和计算工具,应用于电压依赖性阴离子通道和线粒体模型开发
- 批准号:
2153376 - 财政年份:2022
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Collaborative Research: Defining functions of an essential, conserved protein that uniquely links the mitochondrial matrix with the cytoplasm
合作研究:定义一种重要的、保守的蛋白质的功能,该蛋白质将线粒体基质与细胞质独特地连接起来
- 批准号:
2215730 - 财政年份:2022
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Collaborative Research: Defining functions of an essential, conserved protein that uniquely links the mitochondrial matrix with the cytoplasm
合作研究:定义一种重要的、保守的蛋白质的功能,该蛋白质将线粒体基质与细胞质独特地连接起来
- 批准号:
2215727 - 财政年份:2022
- 资助金额:
$ 92.05万 - 项目类别:
Standard Grant
Investigative research on the extention of healthy lifespan that can be applied to humans based on mitochondrial unfolded protein response
基于线粒体未折叠蛋白反应的可应用于人类的延长健康寿命的调查研究
- 批准号:
20KK0228 - 财政年份:2020
- 资助金额:
$ 92.05万 - 项目类别:
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))