MRC National Institute for Medical Research, London
Science for Health
Eva Frickel group project:
Characterization of the IFNy-inducible class of p65 GTPases during infection with Toxoplasma gondii
Among the proteins highly upregulated as a consequence of interferon-stimulated transcription are the p65 GTPases (GBPs), members of the family of large GTPases that mediate resistance to intracellular pathogens. Contrary to the p47 class of GTPases, the GBPs are present in multiple copies in both the mouse and human genome.
Even though the structure of human GBP1 has been solved and the ability of some family members to hydrolyze GTP to GDP and then to GMP is established, limited in vivo role for this class of enzymes have been assigned. The antimicrobial profile of the p65 GBPs is currently restricted to viruses and few interaction partners are known.
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We have shown that several mouse GBPs are highly expressed in IFNγ-induced cells in vitro upon infection with the parasite, and accumulate at the PV of avirulent type II and III, but not virulent type I strains of Toxoplasma. This property is at least in part dependent on the secreted Toxoplasma proteins Rop16, Rop18 and Gra15. Moreover, we reported that some mouse GBPs (namely mGBP1, mGBP2 and mGBP5) interact at the PV in an IFNγ-dependent manner, suggesting they act jointly in order to combat Toxoplasma.
We will investigate the mode of action as well as the function of this class of GTPases on the vacuole of Toxoplasma in a parasite virulence-dependent fashion.
Frickel group
Recent publications
Research projects
- Properties and phenotype of memory CD8 T cells in the Toxoplasma gondii-infected brain
- Characterization of the IFNy-inducible class of p65 GTPases during infection with Toxoplasma gondii
Frickel biography
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