Nicolas BLANCHARD Ph.D. Immunology, Engineer
Course and current status
Mar 2010-now : “Avenir-ATIP” team leader, Center of Pathophysiology of Toulouse-Purpan, INSERM UMR1043-CNRS UMR5282-Université de Toulouse
Eukaryotic intracellular parasites : immunity and pathophysiology
Jun 2004-Feb 2010 : Post-doctoral fellow, Shastri laboratory, University of California, Berkeley
Mechanisms of MHC class I antigen processing in mouse models of infection with the Toxoplasma gondii parasite and the mCMV virus
Mentor : Dr Nilabh Shastri
2000-2004 Ph.D. thesis, INSERM U365 (Head : Dr Sebastian Amigorena), Institut Curie, Paris
Immunological synapses formed by CD4+ T cells : mechanisms of formation and functional roles
Thesis advisor : Dr Claire Hivroz
Mar 2001 EMBO practical course, European Molecular Biology Lab, Heidelberg, Germany
Imaging and manipulation of biochemical reactions in living cells and organisms
1999-2000 M2R, INSERM U520 (Heads: Dr S. Amigorena & C. Bonnerot), Institut Curie, Paris
T cell activation-induced production of microvesicles bearing CD3/TCR/zeta complexes
Advisor : Dr Claire Hivroz
1999 Engineer Diploma from Ecole Polytechnique
When invaded by infectious microorganisms, cells of the immune system present fragments of these pathogens (antigens) via MHC molecules on their cell surface. Antigen presentation leads to stimulation of T lymphocytes expressing receptors that specifically recognize the cognate peptide antigens. These processes are paramount to eliminate or contain the infection. However, in case of dysregulation, it can also lead to deleterious immunopathological manifestations.
In the lab, we are trying to understand the mechanisms that allow the processing of antigenic peptides during infections caused by intracellular apicomplexan parasites. We study two fascinating examples of such parasites : Toxoplasma gondii (T. gondii) and Plasmodium, respectively causing toxoplasmosis and malaria.
Both parasites live within a vacuole inside the cells. Malaria takes an enormous toll on human lives, especially among children in sub-Saharan Africa where it is responsible for a serious and deadly form called cerebral malaria. Cerebral malaria is characterized by the sequestration of parasitized erythrocytes, but also of immune cells, within brain microcapillaries. Toxoplasmosis is an opportunistic disease that can lead to neurological problems in immunocompromised individuals (e.g. AIDS patients) and can have serious consequences for the fetus if contracted during pregnancy. T. gondii cysts can persist indefinitely in an infected host. In addition, T. gondii is an attractive model because several strains are fully sequenced and are genetically tractable.
We use mouse models for our studies on these two pathogens. For T. gondii, we take advantage of our recent discoveries of natural parasite antigens, particularly the GRA6 secreted antigen which is protective and immunodominant (i.e. induces large populations of CD8 T cells during infection). For Plasmodium, we are aiming to characterize the natural antigens recognized by T lymphocytes during blood stage in order to generate similar tools.
We are pursuing two major goals :
1 - Understand the molecular and cellular bases that give parasite proteins access to he MHC I presentation pathway and, more globally, that may modulate host-parasite interactions
2 - Characterize the protective versus pathological roles of T cells observed during Plasmodium infection