INTEGRATED EXPERIMENTAL AND COMPUTATIONAL RESEARCH TOOLS FOR THE STUDY OF ACUTE ISCHAEMIC EFFECTS ON CARDIAC MECHANO-ELECTRICAL INTERACTIONS
用于研究心脏机电相互作用的急性缺血效应的综合实验和计算研究工具
基本信息
- 批准号:EP/F042868/2
- 负责人:
- 金额:$ 12.7万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Fellowship
- 财政年份:2011
- 资助国家:英国
- 起止时间:2011 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The heart is an electrically controlled mechanical pump, a bit like an electric motor. Similar to an electric motor in 'dynamo mode', the heart is able to translate mechanical interventions into electrical signals.This mechano-electric feedback (MEF) can be observed at all levels of structural and functional integration of the heart, from the molecular level, to whole organ and organism. In patients, MEF effects may both cause and terminate heart rhythm disturbances, which make MEF an important research target for the Life Sciences. However, MEF involves a complex range of interdependent regulatory pathways, which make it difficult to study MEF, even in normal tissue. Most real-life scenarios pose an even greater challenge, as in most patients, MEF effects occur on the background of myocardial ischaemia (where the heart is starved of oxygen / the most common cause of heart rhythm disturbances). Currently, we know neither the mechanisms underlying MEF effects on heart rhythm in ischaemic heart disease, nor the potential and limitations of MEF for heart rhythm management. This is largely caused by a lack in suitable experimental and theoretical models, and I wish to tackle this shortfall in the present proposal.My goal, therefore, is to develop and integrate a suite of advanced 'wet' experimental and 'dry' computational research techniques to study the effects of myocardial ischaemia on cardiac mechano-electrical cross-talk. This will involve technological developments involving isolated heart tissue kept in normal and ischaemic conditions, direct (microelectrodes) and non-contact (optical techniques) mapping of electrical activity, high-speed video-macroscopy of regional tissue deformation, pharmacological interventions that target SAC, and the application of advanced computational models of heart muscle, which will allow me to re-integrate the diverse range of recorded data to aid analysis, interpretation, and prediction.Thus, the approach will combine advanced engineering, biological experimentation, and systematic application of computational tools, to arrive at an integrated systems view of the complex interrelation of cardiac MEF and ischaemia. Tangible outcomes include, in addition to the development of an advanced experimental technique to study hitherto inaccessible life science questions, the provision of novel insight into a clinically relevant aspect of basic cardiac functionality, and the development of computational resources to conduct theoretical experiments and identify promising research targets for experimental follow-up (which will help to Reduce, Refine, and partially Replace 'wet' experimentation). These tools will be applicable to a wider range of research questions, such as more severe stages of ischaemic heart disease, or pathological changes in heart structure, and provide a way to test new devices or pharmacological treatments.This project is also an important step in my career development. I wish to gain new skills to help me study mechanisms of interaction between the mechanical and electrical properties of the heart in more depth. I believe that combining experimental and mathematical modelling is the key to understanding complex biological systems and the processes by which normal behaviour deteriorates into disease. My host teams at the University of Oxford offer a unique combination of these skills and are experts in my chosen field of study. In addition, the opportunity to work with world-leading experts at other universities during this EPSRC Fellowship will give me the chance to learn from some of the best current-day researchers in my field (which is a unique and very important aspect of the present fellowship programme).
心脏是一个电控机械泵,有点像电动马达。就像‘发电机模式’中的电动马达一样,心脏能够将机械干预转化为电信号。这种机电反馈(MEF)可以在心脏结构和功能整合的各个层面上观察到,从分子水平到整个器官和有机体。在患者中,MEF效应可能导致和终止心律失常,这使得MEF成为生命科学的重要研究目标。然而,MEF涉及一系列相互依赖的调控途径,这使得研究MEF变得困难,即使在正常组织中也是如此。大多数现实生活中的情景构成了更大的挑战,因为在大多数患者中,MEF效应发生在心肌缺血(心脏缺氧/心律失常的最常见原因)的背景下。目前,我们既不知道MEF对缺血性心脏病心率影响的潜在机制,也不知道MEF在心律管理方面的潜力和局限性。这在很大程度上是由于缺乏合适的实验和理论模型,我希望解决目前提案中的这个不足。因此,我的目标是开发和集成一套先进的“湿”实验和“干”计算研究技术,以研究心肌缺血对心脏机电串扰的影响。这将涉及到技术开发,涉及正常和缺血条件下保存的孤立心脏组织,电活动的直接(微电极)和非接触(光学技术)标测,局部组织变形的高速视频宏观观察,针对SAC的药物干预,以及先进的心肌计算模型的应用,这将使我能够重新整合各种记录的数据,以帮助分析、解释和预测。因此,该方法将结合先进的工程、生物实验和计算工具的系统应用,以达到心脏MEF和缺血的复杂相互关系的综合系统观点。具体的成果包括,除了开发一种先进的实验技术来研究迄今为止难以触及的生命科学问题外,还提供了对基本心脏功能的临床相关方面的新见解,以及开发了计算资源来进行理论实验并为实验后续工作确定有前景的研究目标(这将有助于减少、改进和部分取代“湿”实验)。这些工具将适用于更广泛的研究问题,如更严重的缺血性心脏病阶段,或心脏结构的病理变化,并提供一种方法来测试新的设备或药物治疗。这个项目也是我职业发展的重要一步。我希望获得新的技能,以帮助我更深入地研究心脏机械和电学特性之间的相互作用机制。我认为,将实验和数学建模结合起来,是理解复杂的生物系统以及正常行为恶化为疾病的过程的关键。我在牛津大学的东道主团队提供了这些技能的独特组合,他们都是我选择的研究领域的专家。此外,在EPSRC奖学金期间与其他大学的世界领先专家合作的机会将使我有机会向我所在领域的一些当今最好的研究人员学习(这是本奖学金计划的一个独特且非常重要的方面)。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Concurrent optical mapping of voltage and calcium in rat isolated hearts using one camera
使用一台相机同时光学测绘大鼠离体心脏的电压和钙
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Bollensdorff C
- 通讯作者:Bollensdorff C
Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve.
- DOI:10.1016/j.pbiomolbio.2016.01.008
- 发表时间:2016-01
- 期刊:
- 影响因子:3.8
- 作者:Dutta S;Mincholé A;Zacur E;Quinn TA;Taggart P;Rodriguez B
- 通讯作者:Rodriguez B
Rediscovering the third coronary artery.
重新发现第三冠状动脉。
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:39.3
- 作者:Burton RA
- 通讯作者:Burton RA
Recent human ventricular cell action potential models under varied ischemic conditions
最近不同缺血条件下的人心室细胞动作电位模型
- DOI:
- 发表时间:2013
- 期刊:
- 影响因子:0
- 作者:Dutta S
- 通讯作者:Dutta S
Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia.
- DOI:10.1016/j.pbiomolbio.2016.06.003
- 发表时间:2016-07
- 期刊:
- 影响因子:3.8
- 作者:Gemmell P;Burrage K;Rodríguez B;Quinn TA
- 通讯作者:Quinn TA
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Thomas Quinn其他文献
The Conservative Party’s leadership election of 2016: choosing a leader in government
2016年保守党领导人选举:选出政府领导人
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:1.1
- 作者:
Thomas Quinn - 通讯作者:
Thomas Quinn
Electing and Ejecting Party Leaders in Britain
选举和罢免英国政党领导人
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
Thomas Quinn - 通讯作者:
Thomas Quinn
Aptamer-HYNIC-<sup>99m</sup>Tc: A molecular imaging agent of PTK7
- DOI:
10.1016/j.nucmedbio.2014.05.010 - 发表时间:
2014-08-01 - 期刊:
- 影响因子:
- 作者:
Victoria Calzada;Marcelo Fernández;Joel González;María Moreno;Alejandro Chabalgoity;Hugo Cerecetto;Pablo Cabral;Thomas Quinn - 通讯作者:
Thomas Quinn
Throwing the rascals out? Problems of accountability in two‐party systems
两党制下的问责问题?
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
Thomas Quinn - 通讯作者:
Thomas Quinn
Thomas Quinn的其他文献
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{{ truncateString('Thomas Quinn', 18)}}的其他基金
Collaborative Research: Galactic Winds and the Multiphase Structure of the Circum-Galactic Medium
合作研究:银河风和环银河介质的多相结构
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2205724 - 财政年份:2022
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
In Situ Formation of Short Period Terrestrial Planets
短周期类地行星的原位形成
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2006752 - 财政年份:2020
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
OAC Core: Small: Collaborative Research: Scalable distributed algorithms for tree structured astronomical data
OAC 核心:小型:协作研究:树结构天文数据的可扩展分布式算法
- 批准号:
1906829 - 财政年份:2019
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
SI2-SSI: Collaborative Research: Paratreet: Parallel Software for Spatial Trees in Simulation and Analysis
SI2-SSI:协作研究:Paratreet:仿真和分析中的空间树并行软件
- 批准号:
1550234 - 财政年份:2016
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
Unified Modeling of Galaxy Populations in Clusters
星系团中星系群的统一建模
- 批准号:
1613674 - 财政年份:2016
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
Collaborative Research: A Holistic Approach to Modeling Galaxy Clusters
协作研究:星系团建模的整体方法
- 批准号:
1514868 - 财政年份:2015
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
Collaborative Research: CDS&E: Evolution of the high redshift galaxy and AGN populations
合作研究:CDS
- 批准号:
1311956 - 财政年份:2013
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
Evolution of the Small Galaxy Population From High Redshift to the Present
小星系群从高红移到现在的演化
- 批准号:
1144357 - 财政年份:2012
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
Use of CR1 Insertions to Dissect a Deep Polytomy in Anseriformes
使用 CR1 插入来解剖雁形目深部多切术
- 批准号:
0743605 - 财政年份:2008
- 资助金额:
$ 12.7万 - 项目类别:
Standard Grant
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