Chemical imaging of organelle heterogeneity and dynamics

In eukaryotic systems, organelles are specialized cellular compartments that perform distinct functions critical for maintaining cellular homeostasis and overall organismal fitness. Traditionally, these organelles have been viewed as well-defined, static entities. However, recent advances have revealed that cellular organelles are highly heterogeneous and dynamic, with these properties being closely linked with their activities. Using vibrational microscopy, we uncover the metabolic heterogeneity of lysosomes and reveal how these variations change in response to genetic perturbations and aging. Moreover, by integrating vibrational microscopy with high-throughput genomic screens, we are able to discover new regulatory mechanisms that govern lipid droplet dynamics in association with different fatty acids. These findings and technology platforms will advance our current understanding of how cellular dynamics plays crucial roles in organismal physiology and pathology.