Neuronal-Glia Communication during Axon Injury and Regeneration

由于中枢神经系统和外周靶点之间的信号传递中断，周围神经系统损伤会导致神经功能的丧失。由于感觉、运动或与器官和腺体的沟通受损，影响可能是广泛的。治疗是有限的，通常是手术性质的，并不侧重于改善或延长内源性再生能力。博士项目旨在确定和功能表征雪旺细胞修复计划的内在和外在调节因子，这些调节因子可用作治疗靶点，以维持其神经修复允许状态。参与雪旺细胞修复计划的候选分子将从转录或蛋白质组筛选中挑选出来。然后，这些基因将在两个不同的神经损伤系统中进行功能测试。首先，在微流体室中与来自转基因小鼠系的雪旺细胞和背根神经节神经元进行体外共培养系统，将通过实时成像来确定该基因在神经元-胶质细胞相互作用中的功能。此外，在活体斑马鱼模型中，将使用CRISPR-Cas9突变后对神经再生进行实时成像的双光子激光切割斑马鱼模型，并将研究神经元与神经节的相互作用。

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.