The dynamics of the endoplasmic reticulum

Lead Research Organisation: University of Manchester
Department Name: Physics and Astronomy

Abstract

The endoplasmic reticulum (ER) is a subcellular organelle responsible for many essential processes within the cell, such as protein synthesis and folding, calcium homeostasis and lipid synthesis. It is a membranous structure composed of sheet-like regions and tubules connected at junctions, forming a network. This network is highly dynamic, with tubules and junctions fluctuating over time, new tubules being formed and new connections between tubules forming junctions. The importance of this movement in relation to the function of the ER remains unknown. This interdisciplinary project uses a physics background to shed light on a biological problem - why does the endoplasmic reticulum move?
There are four main aims:
1) To characterise the structure and dynamics of live ER using fluorescence microscopy. Advanced image analysis tools with be combined with polymer physics (a Fourier analysis using a semi-flexible polymer model), active motor theories and machine learning (a Gaussian mixture model). Tubules and tubule junctions are found to conform to a binary classification scheme of either active or thermal.
2) To investigate the dynamics of the lumen of the ER using FRAP, FCS, FLIM and tracking. Does peristalsis occur in the ER lumen?
3) To use super-resolution fluorescence microscopy (STORM and lattice sheet) to characterise the structure of the ER in 3D.
4) To modify the expression of motor proteins in human cells and observe their impact on the dynamics of the ER.'

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509565/1 01/10/2016 30/09/2021
1918187 Studentship EP/N509565/1 18/09/2017 30/09/2021 Hannah Perkins