Molecular mechanisms of nervous system maintenance and protection

The long-term goal of our research is to identify mechanisms that keep the nervous system functioning throughout life and protect it from aging and neurodegenerative disorders. Neuronal structures established early in development need to persist throughout life for proper brain function. Yet physical stresses are exerted on the nervous system by body movements, increase in body size, and injury. Importantly, aging precipitates dramatic alterations in the physiology of all organisms, compromising cellular function, reducing resistance to stress, and increasing the likelihood of developing age-related diseases. Characteristic conditions are late-onset neurodegenerative disorders and cognitive decline. Remarkably, while physical stress and age are known to be strong determinants of these conditions, the molecular mechanisms leading to natural age-related and lesion-related neural deterioration are virtually unknown.

In the lab we take a multidisciplinary approach that includes genetics, molecular biology, cell biology, biochemistry and confocal microscopy to elucidate the mechanisms that protect the architecture and function of the nervous system throughout life. We use the powerful model organism C. elegans, which has a strong track record of contributions to the fields of nervous system development and function, and of aging, to tease apart the molecular mechanisms underlying normal age-dependent brain decline and neuropathological conditions manifested during senescence and traumatic brain injury. Through our research, we have identified several proteins with roles dedicated to long-term neural protection, including a member of the conserved L1CAM family, SAX-7. Given that the development and function of the C. elegans nervous system has a high degree of evolutionary conservation with the mammalian brain, we expect that our research will ultimately provide crucial information to ameliorate the consequences of age-related cognitive decline, neurodegenerative diseases, and brain lesions.