Funding outcome

The cells in our body are routinely exposed to different types of stress, including agents that cause stress by damaging DNA and environmental agents that cause a type of stress that completely changes the metabolism of the cell. There is emerging evidence that one of the underlying causes of neurodegenerative diseases relates to the machinery that controls stress response in the brain. We are working on a protein called DEAD Box 1 (or DDX1) whose main role is to change the structure of RNA, thereby affecting the amount and types of proteins found in a cell. Based on work done in the Godbout Lab, DDX1 is able to interact with another protein called ATM. ATM is defective in ataxia telangiectasia, a disease that manifests in early childhood and is associated with neurodegeneration. Through a collaboration with Dr. Razmik Mirzayans at the Cross Cancer Institute, we have access to a collection of fibroblasts (or cells taken from the skin) obtained from children with ataxia telangiectasia. We are planning on using these fibroblasts to answer fundamental questions about the role of DDX1 and ATM in stress responses. Towards this goal, we will treat normal as well as ataxia telangiectasia fibroblasts with agents that induce stress in the cells, such as arsenite and paraquat. We will examine how these agents affect normal fibroblasts compared to ataxia telangiectasia fibroblasts. Next, we will see how manipulation of DDX1 and ATM protein levels in normal fibroblasts and ataxia telangiectasia fibroblasts affects stress responses. Through the proposed studies, and over the next two years, we will gain insight into the roles of ATM and DDX1 in the cell's ability to handle stress. This information will allow us to move to the next phase of our study, which will be to investigate how ATM and DDX1 protect neuronal cells from stress-induced neurodegeneration.