CV Science

Alexandre Bougdour PhD Cellular Biology

Course and current status

2008-present: INSERM Permanent Scientist (CR1), Institut Albert Bonniot, Centre de Recherche Inserm  U1209 / CNRS UMR5309 / UGA  - Team Host-Pathogen Interactions & Immunity to Infection.

2007-2008: Post-doctoral Fellow at the UMR5163 LAPM, Grenoble in Mohamed- Ali Hakimi’s group; Epigenetic regulation in Toxoplasma gondii.

2004-2007: Post-doctoral Fellow, the National Institutes of Health, Bethesda, (USA), Laboratory of Dr. Susan Gottesman; Regulated proteolysis of the transcription factor RpoS in bacteria.

2000-2004: PhD, Joseph-Fourier University, Grenoble (France), Laboratory of Pr. Hans Geiselmann; Transcriptional regulation in Escherichia coli.

Scientific summary

  During my PhD I studied the mechanisms of transcriptional regulation in Escherichia coli. I have demonstrated that the Sigma S subunit of RNA polymerase is positively regulated by the atypical protein Crl through direct protein-protein interactions.

During my post-doctoral fellowship in Dr. Susan Gottesman's laboratory, I studied another aspect of Sigma S regulation in bacteria. We designed a genetic screen to identify novel regulators of Sigma S stability. We identified of novel family of regulators that we named anti-adaptor proteins. These regulators bind to and inhibit the adaptor protein RssB necessary for Sigma S degradation by the intracellular protease ClpXP. Interestingly, each anti-adaptor protein is induced under a specific stress condition leading to the stabilization of Sigma S.

  As a second post-doctoral position in Dr. Mohamed-Ali Hakimi’s team, I studied transcriptional regulation in the parasite Toxoplasma gondii, the agent responsible of toxoplasmosis. Hakimi's group has pioneered this field of investigation shedding some light on the mechanisms controlling gene expression in this parasite. My contribution to this work was to determine that the cyclopeptidic HDAC inhibitors interfere with Toxoplasma proliferation and differentiation by targeting the enzyme TgHDAC3. On the clinical side, we discovered new drugs that target a Toxoplasma histone deacetylase and initiate the development of selective and sterilizing drugs against toxoplasmosis and, likely, against malaria.

My current work focuses on the basis of host cell manipulation by Toxoplasma. Indeed, Toxoplasma offers a very exciting opportunity to study mechanisms that operate between the parasite and its host. Toxoplasma, like the other intracellular pathogens, interferes with host signaling pathways through the action of effector proteins directly delivered into the host cells. While the parasite is known to heavily remodel its host cell upon invasion by interfering with important host signaling pathways, only few effector proteins have been characterized so far. Therefore, by integrating diverse genomic-scale analyses and a genetic approach, we identified several Toxoplasma genes encoding for proteins that are secreted and targeted to the host cell cytoplasm or nucleus. By this approach we identified a novel subfamily of dense granule proteins, namely GRA16 and GRA24, that are secreted and then exported beyond the parasitophorous vacuole to the host cell nucleus of infected cells. Another protein, PSP6 is exported to host cell cytoplasm. Altogether, these data identified the first dense granule proteins capable of trafficking through the parasitophorous vacuole membrane.

  My current working hypothesis is that GRA16 and GRA24 represent a potentially emerging subfamily of exported dense granule proteins that modulate host functions. Similar approaches are ongoing in order to determine the role of other effector proteins during toxoplasmosis. I believe that these investigations offer a unique opportunity to extent our current view of how the parasites interact with their host from the animal to the molecular level. The questions we are adressing now are how many other effector proteins exist? What are their functions? And finaly, how do they traffic through the parasitophorous vacuole?