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Disarming bacterial weapons in the nucleus: functional study of Chlamydia nuclear effectors (NUChLEAR)
Date du début: 1 juil. 2012, Date de fin: 30 juin 2017 PROJET  TERMINÉ 

The high prevalence of Chlamydia infections and the heavy burden they inflict on public health justify the search for novel therapeutic approaches directed against this pathogen. Research on this obligate intracellular bacterium is very difficult, due to substantial technical impediments. One current challenge is to identify bacterial proteins that are required for Chlamydia to survive and proliferate in the host and that could serve as targets in novel therapeutic strategies. In particular, the identification of bacterial proteins implicated in the microbe’s ability to persist in host cells is highly desirable, since current treatments fail to erradicate the resulting chronic infections.Our project is focused on the bacterial proteins that are secreted into the host cell during infection and translocate into the nucleus. Our preliminary work has already identified some of these “nuclear effectors” of Chlamydia. Targetting the “central system” of the host, these proteins are likely essential for infection. We will (i) identify all Chlamydia trachomatis nuclear effectors and define their frame of action (in time and space) during infection, (ii) identify the targets of the nuclear effectors and their roles in infection and (iii) test the hypothesis that nuclear effectors are necessary for the entry into and/or maintenance of the persistent state of infection.Addressing for the first time the full repertoire of “nuclear weapons” of an intracellular bacterium, we will uncover new interactions between the pathogen and the host. This work will lead to the development of rationally-designed drugs that inhibit the activity of the nuclear effectors, thereby disrupting the microbe’s ability to survive in the host. Beyond this medical aim, our study, which lies at the interface between microbiology, cell biology and genome biology, will provide new angles of study to each of these three disciplines and improve our understanding of fundamental cellular processes.