Objective
Bacterial pathogens have developed highly specialized processes to target hosts and establish infection. A recently described weapon, the type III secretion system, transfers toxins from the bacterial cytoplasm into the host cell through a pore formed on the host cell membrane upon cell-to-cell contact. In this project, we will use X-ray crystallography to study PopB and PopD, the two membrane proteins required for pore formation by the nosocomial pathogen Pseudomonas aeruginosa, both in their intrabacterial form and as the finalized ring-like pore.
The structural study of membrane proteins has proven to be a challenging endeavor, mainly due to the difficulties presented by the production and purification of membrane proteins in high amounts. PopB and PopD, however, are expressed in the bacterial cytosol in soluble form, complexed to a chaperone, PcrH; in the host laboratory, such complexes can be expressed and purified in milligram quantities, an absolute requirement for successful crystallization experiments. In addition, the host laboratory has already produced preliminary crystals of the PopB:PcrH complex and has expertise at reconstitution of the PopB/PopD pore. Crystallization trials will be performed with TECAN robotics, available at the IBS, and all data will be collected at the ESRF synchrotron in Grenoble.Highly related type III secretion systems are employed by a variety of other pathogens, such as Yersinia pestis, the causative agent of bubonic plague, and Salmonella typhi, the agent of typhoid fever.
Thus, the structural study of the type III secretion pore from P. aeruginosa will provide crucial information regarding the infectivity processes of other pathogens. Targeting a specific host:pathogen interaction which is crucial for bacterial infectivity, such as type III secretion pore formation, will be of central importance for the potential development of novel vaccines, antibiotics, and treatments against pathogenic infections.
Fields of science (EuroSciVoc)
- medical and health sciences basic medicine immunology
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences clinical medicine oncology
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.