$165,000 awarded to Dr. Ulises Rodríguez Corona, a postdoctoral fellow in Dr. Marlene Oeffinger’s lab at the Institut de recherches cliniques de Montréal (ICRM).
Inside a cell nucleus, many biological processes take place. Two proteins, TDP-43 and FUS, are primarily found inside the nucleus where they play important roles. In ALS, they are mutated and behave abnormally by moving out of the nucleus and aggregating in the cytoplasm. The mislocation of TDP-43 outside the cell nucleus is a hallmark sign of most ALS cases.
Scientists have recently discovered other structures inside the cell nucleus. But instead of having distinct shapes and cell walls, they resemble droplets of liquid that form and dissolve. These liquid droplets, called nuclear speckles, contain proteins and other molecules called RNA that can change protein behaviour.
Preliminary work by Dr. Ulises Rodríguez Corona has shown that specialized fats, called nuclear phosphoinositides (PIs), may stick to TDP-43 and FUS inside nuclear speckles, changing how these proteins behave and move.
With this grant, Dr. Rodríguez Corona will investigate whether PIs stick to TDP-43 and FUS proteins and how that changes their function and movement into and out of nuclear speckles. New understandings about the normal processes that direct TDP-43 and FUS proteins to move and function may lead to potential new treatment options for ALS by normalizing their behaviour.