Measuring LRRK2 Cellular Function in Parkinson’s iPSC-Derived Dopaminergic Neurons

Objective/Rationale:             
We aim to develop a time-lapse, imaging, pharmacodynamic assay for measuring LRRK2 cellular function in dopaminergic (DA) neurons derived from human induced pluripotent stem cells (iPSCs) from Parkinson’s patients with LRRK2 mutations. Studies have shown that mutations in the LRRK2 gene play an important role in the regulation of neurite growth and integrity in DA neurons. We will characterize the dynamics of neurite growth, connectivity and degeneration to establish dynamic cellular phenotypes specific to LRRK2 function.

Project Description:             
Our experiment consists of high-throughput, time-lapse microscopy imaging of LRRK2 iPSC-derived DA neurons. We will use computer vision software to measure neuronal health and dynamics and machine learning algorithms to establish dynamic cellular phenotypes specific to LRRK2 function.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
Our assay will be useful for characterizing the effect of LRRK2 inhibitors and other small molecules on neuron function in vitro, and will be made commercially available. This tool could speed development of therapies that could limit or reverse neurodegeneration in Parkinson’s disease.

Anticipated Outcome:          
Through the use of automated, large-scale microscopy-based examination, we expect to uncover cellular phenotypes specific to LRRK2 function based on neuronal dynamics such as neurite outgrowth and connectivity.