Grant: Operating Grant - Priority Announcement: Neuromuscular Research

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of specialized neurons that control voluntary movement. The basis of how these specialized neurons, known as motor neurons, are lost in ALS remains unknown. Environmental influences have long been linked to ALS and motor neurons are known to be very sensitive to chemicals and environmental stress. Mammalian cells possess a variety of mechanisms to mount a stress response and thus mediate a cell's recovery from physiological and environmental stresses. We have recently identified TDP-43 (TAR DNA binding protein) as a regulator of one cellular stress response: the formation of stress granules. TDP-43 mutations are causative for ALS. Thus, this project is aimed at exploring the cell biology of stress granule dynamics mediated by TDP-43 and understanding how disease-causing mutations may disrupt these processes.