Neuronal-Glia Communication during Axon Injury and Regeneration

外周神经系统损伤是由于中枢神经系统与外周目标之间的信号中断而导致神经功能丧失。由于感觉、运动或与器官和腺体的沟通障碍，影响范围可能很广。治疗是有限的，通常是手术性质的，并且不关注于改善或延长内源性再生能力。博士项目旨在识别和功能表征雪旺细胞修复程序的内在和外在调节因子，这些调节因子可以用作治疗靶点，以维持其神经修复许可状态。参与雪旺细胞修复程序的候选分子将从转录组学或蛋白质组学筛选中选择。这些基因将在两种不同的神经损伤系统中进行功能测试。首先，将利用转基因小鼠的神经鞘细胞和背根神经节神经元在微流控室中体外共培养系统，利用实时成像技术确定该基因在神经元-神经胶质相互作用中的功能。此外，在活体斑马鱼模型中，将使用CRISPR-Cas9诱变技术对2光子激光直切斑马鱼进行神经再生的实时成像，并研究神经元-胶质相互作用。

Peripheral nervous system injury leads to loss of neurological function due to the disruptionof signalling between the central nervous system and peripheral targets. Effects can be widerangingdue to impairments in sensation, movement, or communication to organs and glands.Treatments are limited, often surgical in nature, and do not focus on improving or prolongingthe endogenous capacity to regenerate.the PhD project aims to identify and functionally characterise intrinsic andextrinsic regulators of the Schwann cell repair programme that could be used as therapeutictargets to maintain their nerve repair permissive state. Candidate molecules withinvolvement in the Schwann cell repair programme will be selected from transcriptomic orproteomic screens. These genes will then be functionally tested in two different systems fornerve injury. Initially an in vitro coculture system in microfluidic chambers with both Schwanncells and dorsal root ganglion neurons from transgenic mouse lines will be used to determinethe function of the gene in neuronal-glia interactions using live imaging. Furthermore, in vivozebrafish models will be used where live imaging of nerve regeneration will be performedfollowing CRISPR-Cas9 mutagenesis in 2-photon laser axotomised zebrafish and neuronal-gliainteractions will be investigated.