Award details

Determination of the spatial and temporal parameters governing protein translocation pathways

Reference	BB/C00437X/1
Principal Investigator / Supervisor	Professor Colin Robinson
Co-Investigators / Co-Supervisors	Dr Markus Kirkilionis
Institution	University of Warwick
Department	Biological Sciences
Funding type	Research
Value (£)	422,315
Status	Completed
Type	Research Grant
Start date	01/04/2005
End date	30/09/2008
Duration	42 months

Abstract

Protein translocation is a major and essential process in all cells. Protein targeting pathways ultimately underpin the entire system of subcellular compartmentation in eukaryotic cells, and are required in prokaryotes to transport large numbers of proteins across the plasma membrane. To date, most of these systems have been studied using in vitro translocation assays that involve the translocation of very low amounts of radiolabeled protein across isolated membranes. In addition, bioimaging studies and mutant strains have been valuable for the analysis in vivo of the overall targeting pathways. While these studies provide information on the overall pathways and components involved, several aspects of the overall process are poorly understood and this applies particularly to the dynamics and kinetics of the translocation pathways. In this application we propose to use novel approaches to obtain details of the kinetic behaviour of two key protein targeting pathways. In the twin-arginine translocation (Tat) pathway, proteins are transported across the membrane from one soluble phase to another. In contrast, proteins are transported within vesicles to two different forms of vacuole within higher plants. Two broad approaches will be used to obtain a detailed estimate of key kinetic and spatial parameters for each pathway. High quality, quantitative data on each element of the pathways will be obtained using novel bioimaging techniques that enable the bulk flow of substrate to be followed in both time and space. In parallel, mathematical modelling and simulation will use these spatial and temporal data to reconstruct the protein transport systems in detail. This involves the topological computer reconstruction of membranes and organelles, the reconstruction of transport kinetics across membranes by investigating appropriate kinetic schemes and volumetric protein interactions. A spatially explicit sensitivity analysis will be developed to identify key parameters of the processes. This in turn will be used in experimental design to increase data accuracy, for example by determining respective spatial or temporal scales. Finally the computer models will make testable predictions of spatio-temporal protein distributions for all translocation pathways under investigation.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	Plant Science, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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