Bacterial and Toxin Engineering to Treat Motor Neuron Degeneration
Mammalian hosts are constantly exposed to gut-resident bacteria and to bacterial pathogens in the environment. It is increasingly clear that bacteria can signal to the nervous system to regulate neurophysiology, CNS inflammation, and neurodegeneration. Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron degenerative disease with few effective treatments. In this project, we investigate the role that bacteria play in regulating neurodegeneration in ALS. Our major goals in this project are to: a) Determine whether the gut microbiome alters inflammation, neuronal loss, and disease progression in ALS mice; b) Determine whether bacterial infections trigger neurodegeneration; and c) Engineer a specific bacterial toxin to deliver pro-survival factors into motor neurons to treat ALS. Utilizing bacterial manipulation or engineering their toxins to modulate neurotoxicity could be transformative approaches to treat devastating motor neuron diseases.