Open_iPSC_derived_neurons

The impact of genetic variants on molecular pathways that give rise to neurodegenerative diseases such as Alzheimer's and Parkinson's is best elucidated in the appropriate cell types and molecular contexts. Existing studies have focused on bulk profiling of mixed cell types, but have ignored assaying genetic effects across development and cell differentiation. At the core of this proposal is the idea to use single-cell assays to study genetic effects during differentiation of dopaminergic and cortical neurons to identify the sequence of molecular events from variants to healthy and diseased cell states in a cell-specific manner. Characterise intra-individual variation of cell types and single-cell states across cortical and dopaminergic differentiation. - Identify regulatory variants and gene targets that affect transcriptome level, cell-to-cell heterogeneity and the dynamics of cell differentiation. - Optionally: characterize the impact of engineered disease variants and mutant lines.