Identification of Novel Dopamine Signaling Components Using C. Elegans Genetic Analysis

Neurons communicate with one another in the brain using the neurotransmitter dopamine and this communication is critical for normal brain function. In Parkinson's patients the neurons that make dopamine die and, as a result, the ability of these neurons to communicate is lost. At this basic level, there are essentially two ways to treat the symptoms of Parkinson's disease. The first is widely used today and that is to supply the brain with a source of dopamine to compensate for the dopamine that has been lost as a result of neuron death. However, dopamine cannot access the brain from the blood stream, and so another molecule known as L-dopa has been used. L-dopa is converted into dopamine once it enters the brain. Unfortunately, the very same neurons in the brain that are lost in Parkinson's patients are the neurons that convert L-dopa into dopamine. As a result, the effectiveness of L-dopa as a treatment for Parkinson's disease is limited. The second way to treat the symptoms of Parkinson's disease is to develop drugs that interact directly with the neurons that normally receive the dopamine signal. These neurons are not lost in Parkinson's patients. My goal is to identify the molecules within these dopamine-receptive neurons that are important for normal dopamine response. These molecules will represent new and highly specific targets for the development of drugs for the treatment of Parkinson's disease. Because identifying such molecules in human nerve cells is very difficult and time consuming, we will study dopamine signaling in a much simpler organism, C. elegans. C. elegans is a microscopic worm found in the soil that also uses dopamine as a neurotransmitter. In fact, the neurons of these worms communicate with each other in a way that is very similar to the way in which neurons in humans communicate. We plan to identify the molecules required for response to dopamine in C. elegans neurons using genetic analysis and then determine if those same molecules also function in human neurons.