Danielle Grotjahn, Ph.D.

Research

The Grotjahn lab will produce the first structural models that describe how cells assemble the molecular machinery that governs programmed cell death. In multicellular organisms, cells that are unhealthy or no longer needed are removed by a tightly regulated process of cell suicide called apoptosis. This program is orchestrated by mitochondria, subcellular structures that not only generate cellular energy, but can release factors that will direct a damaged cell to self-destruct. The release of these factors is enabled by shaping and pore-forming proteins that interact to promote the restructuring and permeabilization of the mitochondrial membrane. I single-handedly established a facility at Scripps Research for performing high-resolution cellular imaging using cryo-electron tomography. Coupling this approach with multilevel methods in structural, chemical, and computational biology, I will capture and combine information from high-resolution snapshots that reveal how apoptosis-promoting signals recruit these remodeling proteins to the mitochondrial outer membrane and determine how their interaction remodels membrane architecture to facilitate cell death. My studies will lay the framework for uncovering complex subcellular structures. This technology can lead to the development of novel therapeutic targets for treating a myriad of human disorders associated with mitochondrial dysfunction and aberrant apoptotic signaling, from cancer to aging.