Funded Studies
Study Rationale: Parkin is a protein that is encoded by a gene which is frequently mutated in Parkinson’s disease. It is known to be involved in getting rid of damaged mitochondria in cells and this process is deficient in PD patients. The aim is to generate a fluorescent sensor to detect Parkin activity, which can be used to study its behavior in cells. This will lead to provision of cell models incorporating the sensor which can be then used by academia and industry to screen for chemicals which promote Parkin activity.
Hypothesis: We propose that the large conformational change, which Parkin is known to undergo upon activation, can be harnessed to develop a fluorescent sensor of Parkin activity.
Study Design: We propose to engineer the Parkin gene, so that it incorporates two elements that render it fluorescent. The fluorescence properties of the engineered protein will depend upon how close these elements are to each other. Combined with a powerful microscope we will be able to visualize the engineered protein in living cells and gauge where it is and how much of it is “switched on” under a given condition. Once we have optimized the signal and response, we intend to produce standardized cell lines containing the engineered Parkin for wide scale use by the research community.
Impact on Diagnosis/Treatment of Parkinson’s disease: We will develop this into a platform suitable for drug screening, hoping to enable the discovery of drugs that can correct for defects in the disposal of mitochondria that is widespread in Parkinson’s patients.
Next Steps for Development: We hope this will lead to the identification of novel compounds with clinical potential, which would need to be optimized for pre-clinical studies.