Study Rationale:
The leucine-rich repeat kinase 2 (LRRK2) protein is an important player that contributes to Parkinson's disease (PD). Unfortunately, LRRK2 is a large and complex protein that is difficult to study. This project aims to generate a fluorescent (tag that "lights up" a protein) version of endogenous (native) LRRK2 in cells. The fluorescent LRRK2 will be much easier to visualize and will help us determine where LRRK2 is expressed and if/how the expression of LRRK2 changes in PD.
Hypothesis:
This study aims to generate new tools to enhance our understanding of where LRRK2 is expressed and if/how expression or localization changes under certain pathological condition, such as PD.
Study Design:
The CRISPR/CAS9 method (a technique used to change an organism's genes)
will be used to modify the LRRK2 gene in cells so that a fluorescent version of the LRRK2 protein will be expressed instead of normal LRRK2. Imaging and microscopy studies will be performed to determine the success of the generated models.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Understanding if/when/how the LRRK2 protein changes in PD is essential for determining if/when drugs could be used to modify LRRK2 function.
Next Steps for Development:
The proposed tools will be invaluable for use in pre-clinical models of LRRK2 to help determine if, when and where LRRK2 compounds may be administered to people with PD.