Discoveries from the genetic group show us that there are numerous gene mutations in varied proteins that are involved in the development of Parkinson’s disease (PD). With an intimate understanding of how each of these proteins functions in the cell, it is our hope to determine what goes wrong when a protein is harboring a PD causing mutation.
To investigate this we have to generate the tools necessary to study these proteins. We employ a pipeline that includes tagging the PD associated protein so it can be exogenously expressed and detected in primary neurone cultures and creating antibodies against the endogenous protein. We look at both wildtype and PD mutant versions of the proteins. We examine the cell biology and biochemistry of these proteins and assess their neurone specific normal functions and any dysfunction caused by the mutation.
We use a variety of techniques including co-immunoprecipitation, sub-cellular fractionation, immunofluorescence, live cell imaging and different enzymatic assays. Once we find a dysfunction associated with the mutant protein we move into pharmacology and try to find ways to correct what is going wrong at the cellular level with respect to our proteins of interest.