Lipids are essential molecules for life. Cells use lipids to store energy, build membranes, and for cell signaling. We are using state-of-the-art microscopy techniques to study organelle dynamics and lipid trafficking within and between cells.
Lipid trafficking within cells. Within cells, lipids are stored in an organelle called the lipid droplet (LD). LDs are composed of a core of neutral lipids, surrounded by a phospholipid monolayer in which proteins are embedded. LDs make frequent contacts with other cellular compartments, presumably in order to exchange lipids. However, which lipids are being transferred, the direction of transfer, and how these LD-organelle contacts are regulated are unknown. We are using candidate and unbiased approaches to identify proteins involved in lipid droplet-organelle contact sites, and to study the physiological function of these contacts.
Fatty acid trafficking between cells. Fatty acids can transfer between cells within a tissue, but the molecular mechanisms of transfer remain unclear. We are particularly interested in fatty acid transfer between cells in the central nervous system. Neurons are one of the few cell types that do not store lipids in LDs. However, neurons require fatty acids for energy and to build their extensive membranes. We are studying mechanisms of fatty acid transfer from astrocytes to neurons, which has implications for both neurodevelopment and neurodegenerative diseases.
Organelle dynamics in development and neurodegeneration. Eukaryotic cells are divided into membrane-bound compartments called organelles, each with distinct biochemical functions. Organelles undergo dramatic changes in shape, position, dynamics, and interactions with other organelles in response to a variety of developmental and physiological cues. Emerging evidence indicates that organelle function and communication is dysregulated in multiple neurodegenerative diseases. We are using multispectral imaging to systematically investigate the morphodynamics of seven organelles during the differentiation of induced pluripotent stem cells (iPSCs) into multiple neuronal and glial cell types, in a model of normal development and in cells with neurodegenerative disease-associated mutations.