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Advanced imaging and mathematical modelling of ageing and neurodegeneration in the nervous system

神经系统衰老和神经退行性疾病的高级成像和数学建模

基本信息

批准号：
1791002
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1791002
关键词：
Advanced imaging mathematical modelling ageing

项目摘要

This project is highly interdisciplinary at the cross-roads of mathematical modelling and cell-/neurobiological research involving advanced live imaging, electron microscopy (EM), tomography and genetics. It will investigate processes of ageing and degeneration in the nervous system, focussing on mechanisms underpinning the longevity of axons. Axons are the cable-like (~1mm in diameter, metres-long) extensions of neurons which wire the nervous system. These delicate structures are maintained for many decades in humans. They are key lesion sites in spinal cord injury, trauma and many neurodegenerative diseases (e.g. spastic paraplegia), and we lose 50% of our axons during healthy ageing. The essential structural backbone of axons is formed by continuous bundles of filamentous protein-polymers called microtubules. Disorganisation of these microtubule bundles leads to axon swellings correlating with axon decay, but the underlying mechanisms preventing/causing disorganisation are not at all understood. To gain this understanding, work on this project will use genetically induced MT disorganisation in combination with advanced imaging to capture volume and space relationships (EM) as well as the dynamics of MT disorganisation processes (live imaging). Based on the collected data and existing algorithms for MTs, computational/mathematical models describing MT disorganisation will be developed and the underlying rules deduced.Literature:axons: Prokop, 2013, Neur Dev 8, 17ff.genetics: Prokop, 2013, J Cell Sci. 126, 2331ff.mathematics: Ziebert, 2015, Phys Rev Lett 114, 148101ff.live imaging: Alves-Silva, 2012, J Neurosci 32, 9143ff.EM: Starborg, 2013, Nat Protoc 8, 1433ff.

这个项目是高度跨学科的，在数学建模和细胞/神经生物学研究的十字路口，涉及先进的实时成像，电子显微镜（EM），断层扫描和遗传学。它将研究神经系统老化和退化的过程，重点研究支撑轴突寿命的机制。轴突是连接神经系统的神经元的电缆状延伸（直径约1毫米，长几米）。这些微妙的结构在人类体内维持了几十年。它们是脊髓损伤、创伤和许多神经退行性疾病（如痉挛性截瘫）的关键损伤部位，我们在健康衰老过程中失去了50%的轴突。轴突的基本结构骨干是由被称为微管的连续束的丝状蛋白质聚合物构成的。这些微管束的紊乱导致轴突肿胀，并与轴突衰变相关，但预防/导致紊乱的潜在机制尚不清楚。为了获得这种理解，该项目的工作将使用遗传诱导的MT紊乱结合先进的成像来捕获体积和空间关系（EM）以及MT紊乱过程的动力学（实时成像）。基于收集到的数据和现有的MT算法，将开发描述MT紊乱的计算/数学模型，并推导出潜在的规则。文献：轴突：Prokop， 2013, Neur Dev 8,17 ff。基因工程学报，2013,38(2):531 - 531。数学：Ziebert， 2015，物理通讯114,148101ff。实时成像[J] .中国生物医学工程学报，2012,32(1):973 - 973。EM: Starborg, 2013, Nat Protoc 8, 1433ff。