Submitted Abstract
The human brain is an immensely complex structure. Because of this complexity studies in lower animal models and traditional cell cultures addressing human brain development or modelling of disease processes have clear limitations. However, human induced pluripotent stem cells have the intrinsic potential to form organ like structures, so called organoids, which share similarities with functional human organs. Thereby, these organoids offer the unique opportunity to investigate the development of human organs in vitro. Furthermore, they have a tremendous potential for in vitro disease modelling. Indeed, it recently has been shown that such three-dimensional human cell culture models can be used to model Alzheimer’s disease. Strikingly, this novel model is the first one that recapitulates the two key features of Alzheimer’s disease, neurofibrillary tangles and amyloid-beta plaques.Our lab focuses on Parkinson’s disease, which is the second most common neurodegenerative disease. Since the main region of the brain that is affected in Parkinson’s disease is the midbrain, it is the aim of this proposal to generate human midbrain organoids. These organoids will be generated based on human induced pluripotent stem cells from healthy individuals as well as from Parkinson’s disease patients. After their generation they will be characterized in detail using classical as well as systems biology approaches. This characterization will give us unique insights into the pathways and processes that are active during human midbrain development. Finally, by determining phenotypes in patient derived midbrain organoids it is planned to establish these structures as an advanced in vitro model for Parkinson’s disease.