While powerful for studying pathogenic secreted effectors, structural biology has not been used to a large extent to study effector-host protein interactions. In this proposal, we use known and novel secreted effectors and an experimental pipeline that will provide broad insights into how a model pathogen, Salmonella, subverts host cell function.
Aim 1 simultaneously provides key functional insights into effector protein potency and function using broad set of assays, while at the same time serves as an important selection step to focus structural characterization by the PSI network on the most valuable targets.
Aim 2 provides valuable information about the host proteins and protein pathways, using cross-linking and proteomics, that each effector interacts with and provides the PSI network with a prioritized list of host protein targets for structural characterization.
Aim 3 interrogates possible specific protein-protein interactions and provides a selection of validated protein-protein interactions and possibly ligands for structural characterization by PSI network. Ultimately, structure-function studies of individual secreted effectors are invaluable to the host-pathogen research community. However, the insights into host-pathogen biology gained from this large parallel characterization effort with multiple effectors will advance understanding at a more complete systems level.

Public Health Relevance

Advanced mass spectrometry methods with structure determinations will allow for improved understanding of the interactions between human host proteins and pathogens;this research may lead to new therapies for infectious diseases. The specific pathogen model to be studied here is Salmonella, a pathogen that has been the cause of a number of significant food-borne outbreaks in recent years.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01GM094623-03
Application #
8302342
Study Section
Special Emphasis Panel (ZGM1-CBB-0 (BC))
Program Officer
Edmonds, Charles G
Project Start
2010-09-30
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$1,018,783
Indirect Cost
$311,991
Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352
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