Parkinson’s disease (PD) is a disorder that not only affects the function of our brain, but also of our gut, which are both complex tissues composed of functionally diverse types of cells that need to cooperate for organ function. Around 90 regions of the DNA that we inherit from our parents show differences between people with and without PD. Furthermore, as we develop and age, new, non-inherited DNA mutations may also be acquired in part of our body cells. How such inherited and newly acquired DNA variants function in increasing the risk of developing PD remains however largely unknown.
We hypothesize that these DNA variants can increase or decrease the activity of key (un)known genes in particular types of cells of the brain and the gut, which in turn increases the risk of developing PD.
We will use the expertise of our consortium in analyzing single cells to study the brain and gut from individuals who lived with and without PD. Specifically, gene expression profiling of over 4,500,000 single cells will allow us to discover the genes of which the expression is altered by the DNA variants, and importantly, also in which type of brain and/or gut cells the expression of the gene is disturbed. We will next analyze how these DNA variants change the functioning of these specific cell types, by using our existing models of the fruitfly and of cultured human nerve and immune gut cells.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This study will provide crucial mechanistic insights into how faults in our DNA change the functioning of specific cells in our brains and guts, and thus cause a predisposition to PD.