Regulating Space: Bacterial Mastery of the Host Actin Cytoskeleton
EMSL Project ID
39976
Abstract
Abstract: The host plasma membrane, the landscape for environmental and physical perturbations by many microbial pathogens, enhances or diminishes signal transduction by altering diffusivity and oligomerization of many membrane bound receptors. As a consequence of its importance in cell signaling, microbes have evolved advantageous mechanisms which alter cell membrane morphology. Salmonella, modulates the plasma membrane by rapidly polymerizing and depolymerizing the underlying actin cytoskeleton. Although it has been well established, that polymerization upon Salmonella entry results in membrane ruffling and the entry of Salmonella into non-phagocytic epithelial cells, we hypothesize that Salmonella may in addition downregulate immune response by inhibiting membrane-bound TLR. In this work we propose to build a predictive spatial-temporal, stochastic model of TLR signaling and actin cytoskeleton dynamics. We will perform electron microscopy on epithelial cells at pre-Salmonella infection, and pre- and post-Salmonella entry in order to obtain parameters describing the dynamics of the actin cytoskeleton. We will use this data to construct our mathematical model. We will perform simulations to predict downstream TLR signaling under the conditions of pre-infection and Salmonella entry. We will validate and further refine this model by comparing the model results with live-microscopy imaging using techniques such as single particle tracking. The goals of this research are to determine the impacts that disruption of the membrane cytoskeleton has on immune response. The results of this work and the advancement in experimental and computational methodologies will have broad applications in the scientific community.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2010-10-06
End Date
2013-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
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