Profiling and Defining Parkinson’s Disease
Parkinson’s disease (PD) is an incurable progressive neurodegenerative disorder that affects a growing proportion of the aging population, and its cause is largely unknown. We propose to gain insights into the molecular mechanisms of PD. Our objectives are: 1) Identify alterations in gene expression at a single cell level in PD samples by using powerful droplet microfluidics single-nuclei RNA-seq, single molecule FISH, in situ sequencing and bioinformatics analysis; and 2) Determine the function of genes with altered expression levels and their contribution to PD by using novel gene editing technologies and advanced midbrain differentiation protocols for pluripotent stem cells. Our project will systematically analyze and provide an unbiased understanding of the cell types and molecular mechanisms involved in PD. This will enable us to define molecular pathways, disease subtypes, markers and possible targets for future therapeutic intervention.