The long-standing dilemma when studying subcellular dynamics with optical microscopy is how to acquire the greatest spatiotemporal information with high fidelity and quantifiability but the least photobleaching and phototoxicity possible. In this talk, I will report our latest advances of how to synergize the developments in both optical front-end and algorithmic back-end methodology to address these challenges, and apply them to a wide variety of fragile and rapid evolving subcellular bioprocesses at ultrahigh spatiotemporal resolution...

Glucose is a universal metabolic substrate, yet its role in regulating protein function—particularly during cell fate transitions—remains poorly understood. During epidermal differentiation, intracellular glucose levels rise significantly. Using azido-glucose click chemistry coupled with dextran-based enrichment and mass spectrometry, we discovered that glucose directly binds to several RNA-binding proteins (RBPs), including the RNA helicases DDX21 and DDX50 and the RNA methyltransferase NSUN2—key regulators of epidermal development. Glucose interacts with the ATP-binding domains of DDX21 and DDX50,...

The deep analysis of massive mass spectrometry data has long been a critical challenge in the field of proteomics. Traditional mass spectrometry data analysis methods often exhibit low identification rates due to their inability to effectively search for peptides with unexpected digestion patterns and modifications. We developed the pFind 3 method for deep analysis of mass spectrometry data, which expands the search space by five orders of magnitude, enabling effective searches for peptides with any...

The Hippo pathway has emerged as an evolutionarily conserved signaling network that regulates cell proliferation, tissue homeostasis, and tissue regeneration. We show that the tumor suppressor Merlin, an upstream regulator of the Hippo pathway, forms solid-like condensates that activate Hippo signaling in Drosophila tissues. Merlin condensation required phosphatidylinositol-4-phosphate (PI4P)-mediated plasma membrane targeting, and was antagonistically controlled by Pez and cytoskeletal tension through plasma membrane PI4P regulation. The solid-like material properties of Merlin condensates are essential...