Investigating the transcriptional and functional stress responses in different neuron subtypes after knockdown of mitochondrial complex I subunit ND-7

研究敲低线粒体复合物 I 亚基 ND-7 后不同神经元亚型的转录和功能应激反应

• 批准号: 2779104
• 金额: --
• 依托单位: King's College London
• 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-2779104
• 关键词: Investigating; transcriptional; functional; stress; responses

We hypothesise that mitochondrial complex I inhibition (via knock down of subunit ND-75) will lead to distinct transcriptional and functional stress responses in different neuronal subtypes. To test this hypothesis in the next upcoming months I plan to:1. Analyze the behavioural effects of ND-75 KD in a single neuronal subtype, dopaminergic and serotonergic neurons.Climbing and seizure assaysCAFÉ feeding assayANY-Maze open field assayHot plate assayAnalysis of ATF4 expression- adult brain dissections, staining and confocal microscopy 2. Analyze the transcriptional response caused by ND-75 KD in single neurons. -We will perform single nuclear RNA-seq (snRNA-seq) from flies with pan-neuronal ND-75 KD and ND-75 KD together with ATF4 KD.3. Test whether targeting mitochondrial stress signalling modifies dopaminergic and serotonergic neuron function.

我们假设线粒体复合体I抑制(通过敲除ND-75亚单位)将在不同的神经元亚型中导致不同的转录和功能应激反应。为了在接下来的几个月里检验这一假说，我计划：1.分析ND-75KD对单个神经元亚型，多巴胺能和5-羟色胺能神经元的行为影响。爬升和癫痫分析CAFé摄食分析ANY-迷宫开放式场法热板分析ATF4的表达--成人脑切片、染色和共聚焦显微镜2.分析ND-75KD在单个神经元中引起的转录反应。-我们将对具有泛神经元ND-75KD和ND-75KD的果蝇进行单核RNA-seq(SnRNA-seq)，并与ATF4 KD.3一起进行。测试靶向线粒体应激信号是否改变多巴胺能和5-羟色胺能神经元的功能。