Selective cell vulnerability to alpha-synuclein: investigating the underlying region- and celltype- specific factors

选择性细胞对 α-突触核蛋白的脆弱性：研究潜在的区域和细胞类型特异性因素

• 批准号: 2432506
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2432506
• 关键词: Selective; cell; vulnerability; alpha; synuclein

Investigating factors that make a specific region/cell type, particularly prone to each asynucleinopathy (PD, MSA, DLB). Reproduce each pathology on multiple models: cell cultures, human post-mortem brain tissue, mice, and minibrains of IPS cells. For these the following steps will apply: 1) initialscreening by correlative light-electron microscopy (CLEM) 2) structural characterization and time pattern identification bysuper resolution microscopy 3) microenvironment characterisation by scRNA seq, BioID, histology,immunohistochemistry, oxidative stress assays, calcium imaging 4) test the vulnerability criteria identified bysteps 1-3 both in vitro and in vivo (e.g. by CRISPR or biosensors).

调查导致特定区域/细胞类型的因素，特别是容易发生每种无核症(PD、MSA、DLB)的因素。在多种模型上复制每种病理：细胞培养、人死后脑组织、小鼠和IPS细胞的微脑。为此，将采用以下步骤：1)通过相关光电子显微镜(CLEM)进行初步筛选；2)通过超分辨率显微镜进行结构表征和时间模式识别；3)通过scRNA序列、BioID、组织学、免疫组织化学、氧化应激分析、钙成像等方法表征微环境；4)在体外和体内(例如通过CRISPR或生物传感器)测试步骤1-3确定的易损性标准。