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

微管动力学破坏是许多遗传性运动神经元疾病中神经元选择性易感性的关键机制。微管促进货物沿轴突的长距离运输，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性截瘫8型（HSP8）的微管分子病因，HSP8是一种源于Strumpellin蛋白点突变的运动神经元疾病。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.