Objective/Rationale:
The availability of dopaminergic neurons for in-depth study or therapeutic replacement approaches has traditionally been limited. We aim to reprogram cells into dopaminergic neurons by modifying chromosome structure such that th cells become susceptible to be reprogrammed to dopaminergic neurons.
Project Description:
Two gene regulatory factors, called Nurr1 and Pitx3 are known to be required to generate midbrain dopaminergic neurons in vertebrates. However, these two factors are not able to reprogram cells outside of the midbrain into dopaminergic neurons. We hypothesize that this is due to the presence of certain inhibitory mechanisms and propose to inhibit these inhibitors in several rodent cell lines to see if they then are convertible into dopaminergic neurons.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
One much anticipated approach to tackle PD has been to replace the sick/dying dopaminergic neurons. The provision of enough source material, ideally of idiopathic nature, has been problematic. Our studies may provide a novel avenue for how to generate dopaminergic neurons in vitro.
Anticipated Outcome:
We hope that by removing an inhibitory mechanism we will be able to induce dopaminergic cells in vitro.