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

Lead Research Organisation: King's College London
Department Name: Clinical Neuroscience

Abstract

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 assays
CAFÉ feeding assay
ANY-Maze open field assay
Hot plate assay
Analysis 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.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
NC/V001884/1 01/10/2021 30/09/2024
2779104 Studentship NC/V001884/1 01/10/2021 30/09/2024