Grant: Project Grant

While mental decline and the onset of neurodegenerative diseases are strongly dependent on age, the mechanisms that trigger these conditions are largely unknown. The goal of this project is to understand how brain cells, after birth, are protected lifelong from post-natal growth and maturation, and from the wear and tear of everyday life, with the major goal of uncovering strategies to counteract brain decline and neurodegenerative disorders that manifest during adulthood. We predict that this research strategy will open up novel and powerful advances into our understanding of the long-term protection of the nervous system. Ultimately, these studies are expected to speed up future research in mammalian systems, where genetic approaches to identify genes regulating neuronal maintenance are still quite complicated. The proposed studies in C. elegans are expected to establish a strong foundation to elucidate the molecular and cellular mechanisms of neuronal maintenance, at the single-neuron, circuit, and circuit output (behavior) levels. We expect that our findings will foster the study of novel molecular mechanisms that control neuronal decline, which will dramatically enhance our understanding of the molecular codes used by neurons to actively protect neuronal function despite developmental, mechanical, and environmental challenges. We expect that our research will have fundamental implications for the treatment of neurodegenerative diseases and the development of approaches to ameliorate the consequences of adult-onset neurological conditions, thus improving the quality of human life.