Dendritic cells (DCs) are key players involved in initiation of T cell-mediated immune responses against pathogens and cancer. Priming of antigen-specific T cells relies on the ability of DCs to sample antigens from infected or cancer cells and to present them on MHC class I molecules. This process is referred to as cross-presentation, but the molecular machinery involved is still poorly characterised. We use CRISPR-Cas9 genetic screens, proteomics, and transcriptomics in order to identify key players involved in cross-presentation. Ultimately, we hope to understand how the proteins identified work together to control initiation of immune responses against cancers.

The possible project will involve a wide range of cell biological and immunological in vitro assays, and work with animal models to study contribution of selected genes to immune responses in vivo. The position is best suited for an enthusiastic student in interested how immune responses are initiated at the molecular level.

References

Kozik, P., Gros, M., Itzhak, D., Joannas, L., Heurtebise-Chrétien, S., Krawczyk, P., Rodríguez-Silvestre, P., Alloatti, A., Magalhaes, J., Nery, E., Borner, G., and Amigorena, S. (2020).
Small Molecule Enhancers of Endosome-to-Cytosol Import Augment Anti-tumor Immunity.
Cell Reports 32(2) 107905. doi:10.1016/j.celrep.2020.107905

Grotzke, J.E., P. Kozik*, J.-D. Morel, F. Impens, N. Pietrosemoli, P. Cresswell, S. Amigorena, and C. Demangel. (2017)
Sec61 blockade by mycolactone inhibits antigen cross-presentation independently of endosome-to- cytosol export.
Proceedings of the National Academy of Sciences. 114:E5910–E5919. doi:10.1073/pnas.1705242114.

Alloatti, A., D.C. Rookhuizen, L. Joannas, J.-M. Carpier, S. Iborra, J.G. Magalhaes, N. Yatim, P. Kozik, D. Sancho, M.L. Albert, and S. Amigorena. (2017).
Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.
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Kozik, P.*, N.A. Hodson, D.A. Sahlender, N. Simecek, C. Soromani, J. Wu, L.M. Collinson, and M.S. Robinson. (2013)
A human genome-wide screen for regulators of clathrin-coated vesicle formation reveals an unexpected role for the V-ATPase.
Nature Cell Biology. 15:50–60. doi:10.1038/ncb2652.