Grand Challenge Initiative

The Starr Foundation Program for Discovery Science recently launched the Grand Challenge Initiative (SD-GCI) to catalyze bold, collaborative basic research at Memorial Sloan Kettering. Designed to unite at least three independent laboratories around a single ambitious scientific question, the program empowers teams to tackle problems that cannot be solved by individual labs alone. By fostering synergy across projects, the initiative lays the groundwork for future large-scale, externally funded collaborations. The inaugural project selected exemplifies this vision, bringing together complementary expertise to advance fundamental discovery science in ways that will open new directions for the field.

SD-GCI Projects 

2025-2027

Membrane-directed stress responses as sentinels or organelle dysfunction
PIs: Philip Niethammer, Lydia Finley, Michael Overholtzer

Healthy cells and tissues are maintained by adaptive mechanisms that can sense and respond to stress before it becomes severely damaging. Recent research from our laboratories has uncovered a new type of stress response that involves direct sensing of the extracellular and intracellular environment by organelle membranes, including the nucleus and ER, lysosomes, and mitochondria. “Membrane directed stress responses” are coupled to organelle activity and allow cells to rapidly respond to mitigate damage and mount inflammatory responses, yet how membranes mediate such responses remains poorly understood. Here we propose to uncover how membrane-directed stress responses function and are coordinated across organelle systems by pursuing three projects: