Group Leader at the MRC LMB
Patrycja Kozik is accepting applications for PhD students.
Dendritic cells (DCs) play a key role in initation of immune responses against pathogens and tumours. In order to prime the relevant CD8+ T cells, DCs acquire antigens from infected or cancer cells and process them for presentation on MHC class I molecules. We areCa interested in the signalling events, membrane trafficking pathways, and transcriptional programmes that control processing of captured antigens and the efficiency of T cell priming. We employ proteomics, transcriptomics and CRISPR-Cas9-based genetic screening strategies to identify the players involved and to build a detailed picture of the molecular events that occur in DCs following antigen uptake.
We also aim to understand how intracellular membrane trafficking and signalling pathways are modulated by danger signals associated with viral infection or tumour environment. These signals regulate the efficiency of antigen processing as well as expression of co-stimulatory molecules and, ultimately, determine whether the DC-T cell interaction results in an immunogenic response or, conversely, promotes tolerance.
antigen processing ; cytotoxic T cells (CTL) ; innate immunity ; MHC class II ; MHC ; pattern recognition receptors ; fluorescence microscopy ; proteomics ; FACS ; antigen presentation ; dendritic cells ; genetic screening ; MHC class I
Choma, M., J. Lumb, P. Kozik, and M.S. Robinson. A Genome-wide Screen for Machinery Involved in Downregulation of MHC Class I by HIV-1 Nef. PLoS ONE (2015) vol. 10 (10): e0140404
Kozik, P.*, N.A. Hodson, D.A. Sahlender, N. Simecek, C.S. Soromani, J. Wu, L.M. Collinson, and M.S. Robinson. A human genome-wide screen for regulators of clathrin-coated vesicle formation reveals an unexpected role for the V-ATPase. Nat Cell Biol (2013) vol. 15 (1) pp. 50-60
* joint corresponding author
Borner, G.H.H., R. Antrobus, J. Hirst, G.S. Bhumbra, P. Kozik, L.P. Jackson, D.A. Sahlender, and M.S. Robinson. Multivariate proteomic profiling identifies novel accessory proteins of coated vesicles. J Cell Biol (2012) vol. 197 (1) pp. 141-60
Kozik, P., R.W. Francis, M.N.J. Seaman, and M.S. Robinson. A screen for endocytic motifs. Traffic (2010) vol. 11 (6) pp. 843-55
Toussaint, H., F.-X. Gobert, M. Schindler, C. Banning, P. Kozik, M. Jouve, F. Kirchhoff, and P. Benaroch. Human immunodeficiency virus type 1 nef expression prevents AP-2-mediated internalization of the major histocompatibility complex class II-associated invariant chain. J Virol (2008) vol. 82 (17) pp. 8373-82
Wright, C.A., P. Kozik, M. Zacharias, and S. Springer. Tapasin and other chaperones: models of the MHC class I loading complex. Biol Chem (2004) vol. 385 (9) pp. 763-78