High-resolution light-sheet microscopy for whole-cell sub-cellular dynamics.

Research in the areas of organelle dynamics, cytoskeletal interactions, membrane protrusions, and cell motility relies heavily on live-cell imaging. These structures continuously move about in complex patterns and imaging them live at sufficient temporal resolutions as well as for durations long enough to extract significant number of events is an absolute necessity. Capturing most of the sub-cellular dynamics in whole cell volumes was beyond reach due to the lack of balance between reduced photo-toxicity, time resolution, and the required spatial resolution in dominant imaging modalities like point scanning confocal and spinning disc confocal microscopy.

The physical basis of analog-to-digital signal processing in the EGFR system-Delving into the role of the endoplasmic reticulum.

Receptor tyrosine kinases exhibit ligand-induced activity and uptake into cells via endocytosis. In the case of epidermal growth factor (EGF) receptor (EGFR), the resulting endosomes are trafficked to the perinuclear region, where dephosphorylation of receptors occurs, which are subsequently directed to degradation. Traveling endosomes bearing phosphorylated EGFRs are subjected to the activity of cytoplasmic phosphatases as well as interactions with the endoplasmic reticulum (ER).

Deterministic early endosomal maturations emerge from a stochastic trigger-and-convert mechanism.

Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves a phosphoinositide-driven gain or loss of specific proteins on individual endosomes, emphasising an autonomous and stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole cell-level measurements of absolute numbers of maturation events.