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

该项目涉及数学建模和细胞/神经生物学研究的交叉学科，涉及先进的实时成像、电子显微镜(EM)、断层扫描和遗传学。它将研究神经系统的衰老和退化过程，重点是支撑轴突长寿的机制。轴突是连接神经系统的神经元的缆状延伸(直径约1毫米，长约3米)。这些微妙的结构在人类身上保持了几十年。它们是脊髓损伤、创伤和许多神经退行性疾病(如痉挛截瘫)的关键病变部位，在健康的衰老过程中，我们失去了50%的轴突。轴突的基本结构主干是由被称为微管的连续的丝状蛋白质聚合物束形成的。这些微管束的紊乱导致轴突肿胀，与轴突衰退相关，但预防/导致紊乱的潜在机制根本不清楚。为了了解这一点，这个项目的工作将使用遗传诱导的MT紊乱与先进的成像相结合来捕捉体积和空间关系(EM)以及MT紊乱过程的动态(实时成像)。基于收集的数据和MTS的现有算法，将开发描述MT组织紊乱的计算/数学模型，并推导出潜在的规则。文献：Axons：Prokop，2013，Neur Dev 8，17 f。遗传学：Prokop，2013，J Cell Sci。数学：Ziebert，2015，Phys Rev Lett 114,148101 ff.实时成像：Alves-Silva，2012，J Neurosci 32,9143 ff.EM：Starborg，2013，NAT Protoc 8,1433 ff.

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.