Research Group of Dr Paul Thomas, University of East Anglia

Research Group of Dr Paul Thomas, University of East Anglia

Dr Paul Thomas (center) with Derek Fulton (IT Systems Director) and Alba Warn (Imaging Facility Manager) from the Henry Wellcome Laboratory for Cell Imaging.

Dr Paul Thomas is a member of the School of Biological Sciences at the University of East Anglia , in Norwich , England. He is primarily interested in the mechanisms by which proteins and peptides are released from cells during regulated secretion.

Many cell types synthesize secretory products and store them in vesicles to be released upon stimulation with a relevant chemical or electrical signal. This is known as stimulus-dependent, or regulated secretion. Regulated secretion, in contrast to constitutive secretion, which occurs in all cell types, is associated with cell differentiation and specialization. The acquisition of regulated secretion was critical for the development of numerous physiological regulations, for instance the protection of epithelia by mucins or the regulated secretion of
hormones.

Paul is currently focusing on the secretory pathway of rat pancreatic acinar cells and he has shown that these cells possess two modes of secretion. One mode is employed preferentially in response to physiological concentrations of acetylcholine, whilst the second mode predominates when the cells are stimulated by supramaximal doses. These modes are characterized by their relative sensitivity to the phosphatidylinositol 3-kinase inhibitor wortmannin.

Paul obtained his B.Sc. from the University of London , and moved to the U.S.A. , where he studied for his Ph.D. at the University of California , Davis . He returned to Cambridge in 1997 and in 2003 he joined UEA, where in addition to research and teaching responsibilities, Paul is also Director of the Henry Wellcome Laboratory for Cell Imaging.

This imaging unit has extensive facilities, containing eight fluorescence microscopes, three of which are laser confocal scopes. The unit also has an off-line analysis suite that includes an Improvision License Server system with five Volocity licenses. The ILS provides 3D and 4D visualization, image restoration and analysis tools for all the scientists in the department.

Paul writes, “Our recent studies have implicated a Ca2+ influx pathway in the switching between different modes of secretion. Furthermore, the influx pathway appears to be targeted to mitochondria that decorate the lateral membranes of rat acinar cells (arrowheads, panel A of figure). These mitochondria play a critical role in mode switching, and we have now begun to explore their morphology and localization in other acinar cells. Remarkably, in mouse pancreatic acinar cells the mitochondria have dramatically different morphology, being mainly clustered around the secretory granules (see boxed region in panel B) and putting out long processes (arrow in panel B) that form junctions with the basal plasma membrane. Use of Volocity to perform image restoration and 3D reconstruction of confocal image stacks (panels C & D, derived from boxed region in panel B) has enabled us to view these structures in unprecedented detail.”

Please visit the Thomas website for more information.

3D reconstruction of a series of confocal slices through a cluster of five rat acinar cells (live) stained with MitoTracker Red CMXRos (red) and AM1-43 (green). Cluster of five mouse acinar cells stained with MitoTracker Red CMXRos, fixed and then counterstained with Alexafluor488-labelled phalloidin. Fluorescence images overlaid on the DIC image.

 

3D reconstruction of section of cells from panel B (boxed region) following image restoration using a constrained iterative algorithm and a measured psf.