Grant: Project Grant

Our bodies are inhabited by thousands of bacteria. These bacteria (collectively referred to as the microbiota) are not passive inhabitants, but instead play important roles in metabolism, development of the immune system, and protection against pathogens. In addition to these roles, alterations in the bacterial makeup of the microbiota have been observed in a number of diseases, including neurodegenerative diseases. However, these studies are correlative, demonstrating alterations in already diseased patients; they do not demonstrate a causal role in disease development and do not identify specific factors that contribute to disease. Further investigation is required to determine if, and how, alterations in the microbiota contribute to the development of these diseases. To this end, we are focusing on the potential role of microbiota in influencing neurodegeneration. Our goal is to identify possible interventions that will slow the decline in neuronal function that occurs with age. The development of treatments and interventions designed to target the microbiota requires the identification of specific bacterial factors that influence disease state and an understanding of how these factors work. To accomplish this, an experimental system is needed that allows alteration of the microbiota and where genetic differences between individuals does not exist. We use a small nematode (worm), C. elegans for this purpose. Using these animals, we are able to easily generate large populations (millions) of genetically identical animals for analysis. We will determine the influence of hundreds of bacterial strains isolated from humans, on neurodegeneration using C. elegans models of Parkinson's and Alzheimer's diseases. Using the bacteria that differentially influence neurodegeneration, we will identify specific molecules produced by these bacteria and examine changes in the expression of genes that occur in response to these factors.