ALS Association Investigator Grant
P. Hande Ozdinler, Northwestern University
Neil Kelleher, Northwestern University
Paul Thomas, Northwestern University
Neurons become vulnerable when they fail to maintain cellular homeostasis, which require very complex dynamics of protein-protein interactions. We think that understanding neuronal vulnerability requires investigation of protein landscape of neurons that begin to show signs of degeneration at a cellular level. Previously, it was impossible to investigate the protein content of distinct neuron populations because they are very limited in numbers and the proteomics approaches were not sensitive enough to detect low levels of proteins. Today we are at the crossroad of important discoveries; we now can: 1) isolate pure populations of both healthy and diseased upper motor neurons at different disease stages; 2) determine protein content within pure neuron populations with high precision using top-down, bottom-up proteomics; 3) determine protein-protein interactions that are critically important for neuron function; 4) using well-defined model systems we can test biology-derived and well-educated hypotheses. Our unique strengths, when combined, overcome limitations in the field and allow identification of protein dynamics in vulnerable and degenerating neurons. This information sets the stage for many important discoveries to come, and could potentially identify candidate early detection markers especially for diseases in which upper motor neurons are affected, such as ALS.