Understanding the mechanism of actin-microtubule co-regulation underlying neurodegeneration in motor neurons

微管动力学紊乱是导致神经元在许多不同的遗传运动神经元疾病中选择性易损性的关键机制。微管有助于货物沿轴突的长距离运输，并稳定内质网和线粒体沿神经元的分布。该项目将研究遗传性痉挛截瘫8型(HSP8)基于微管的分子原因，HSP8是一种运动神经元疾病，源于Strumpellin蛋白的点突变。学生将使用广泛的技术解决这个问题，包括神经元的超分辨率活细胞显微镜；信号通路的细胞生物学分析和微管动力学的体外重建。

Disrupted microtubule dynamics are a key mechanism underlying the selective vulnerability of neurons across many different genetic motor neuron diseases. Microtubules facilitate the long range transport of cargo along axons and stabilise the endoplasmic reticulum and mitochondria distribution along neurons. This project will investigate the microtubule based molecular causes of Hereditary Spastic Paraplegia type 8 (HSP8), a motor neuron disease originating from point mutations in the protein Strumpellin. The student will address this question using a wide range of techniques including super-resolution live cell microscopy of neurons; cell biological analysis of the signalling pathways and in vitro reconstitution of microtubule dynamics.