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Reverse mathematical methods for reconstructing molecular dynamics in single cell

Single particle tracking reveals nanofluidic properties of the Endoplasmic Reticulum

speaker: Edward Avezov (University of Cambridge, UK Dimentia Institute Cambridge )

abstract: The Endoplasmic Reticulum (ER), a network of membranous sheets and pipes, supports functions encompassing biogenesis of secretory proteins and delivery of functional solutes throughout the cell periphery. Molecular mobility through the ER network enables these functionalities. The diffusion-driven molecular motion (traditionally presumed by default), alone is not sufficient to explain the kinetics of luminal transport across supramicron distances. Understanding the ER structure-function relationship is critical in light of mutations in ER morphology regulating proteins that give rise to neurodegenerative disorders. Applying super-resolution microscopy and stochastic analysis of single particle trajectories of ER luminal proteins revealed that the topological organization of the ER correlates with distinct trafficking modes of its luminal content: with a dominant diffusive component in tubular junctions and a fast flow component in tubules. Particle trajectory orientations resolved over time revealed an alternating current of the ER contents, whilst fast ER nanoscopy identified energy-dependent tubule contraction events at specific points as a plausible mechanism for generating active ER luminal flow. The discovery of active flow in the ER has implications for timely ER content distribution throughout the cell, particularly important for cells with expensive ER-containing projections e.g. neurons, sanctioning efforts to understand the ER transport through mathematical modeling and biophysical analysis.

Tue 16 Oct, 9:45 - 10:30, Aula Dini
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