2 Post-doc and 2 PhD-student positions available in the protein crystallography group of Piet Gros,
Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands. Structural Biology of the Complement System The human complement system in blood plasma is a protein network consisting of ~30 large multi-domain plasma proteins and cell-surface receptors. Together these proteins recognize and clear invading microbes and apoptotic host cells, linking innate and adaptive immune responses. We study the molecular mechanisms that underlie the biological activity of these complement proteins. Insights into the underlying mechanisms are instrumental to developing therapies that help in fighting infectious diseases, protect humans from complement-induced tissue damage, and possibly help to direct antibodies to clear tumor cells. In recent years we have studied the central "opsonization" step. In this step the target microbe or altered host cell becomes covalently and massively labeled by marker molecules, which evoke various immune responses. Currently we are expanding our research addressing the multivalent complex formations on target cells that determine antibody-mediated recognition, protection of healthy host cells against clearance, stimulation of B-cells and clearance by macrophages. This work involves predominantly mammalian protein expression, crystal-structure determination of large protein complexes, electron microscopy (in coll. with Bram Koster, Leiden University) and single-molecule fluorescence (in coll. with Hans Gerritsen, Utrecht University). Relevant key publications from our group: - Structures of complement component C3 provide insights in function and evolution of immunity, B.J.C. Janssen, E.G. Huizinga, H.C.A. Raaijmakers, A. Roos, M.R. Daha, K. Nilsson-Ekdahl, B. Nilsson and P. Gros, Nature 437, 505-511 (2005). - Structure of C3b reveals conformational changes underlying complement activity, B.J.C. Janssen, A. Christodoulidou, A. McCarthy, J.D. Lambris and P. Gros, Nature 444, 213-216 (2006). - Factor B structure provides insights into the activation of the central protease of the complement system, F.J. Milder, L. Gomes, A. Schouten, B.J.C. Janssen, E.G. Huizinga, R.A. Romijn, W. Hemrika, A. Roos, M.R. Daha and P. Gros, Nature Structural and Molecular Biology 14, 224-228 (2007). - Structure of C8a-MACPF reveals mechanism of membrane attack in complement immune defense, M.A. Hadders, D.X. Beringer and P. Gros, Science 317, 1552-1554 (2007). - Complement driven by conformational changes, P. Gros, F.J. Milder and B.J.C. Janssen, Nature Reviews Immunology 8, 48-58 (2008). - Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor, S.H.M. Rooijakkers*, J. Wu*, M. Ruyken, R. van Domselaar, K.L. Planken, A. Tzekou, D. Ricklin, J.D. Lambris, B.J.C. Janssen, J.A.G. van Strijp and P. Gros, Nature Immunology doi:10.1038/ni.1756 (2009). *These authors contributed equally. - Structure of complement fragment C3b-factor H and implications for host protection by complement regulators, J. Wu, Y.-Q. Wu, D. Ricklin, B.J.C. Janssen, J.D. Lambris and P. Gros, Nature Immunology doi:10.1038/ni.1755 (2009). The selected candidates will work in a small team focused on the complement system. The post-docs will focus on reconstitution of large complexes (up to MDa scale) on membrane surfaces, determine crystal structures and collaborate with outside groups on EM and smFRET. The PhD students will focus predominantly on expression of mammalian proteins and crystal-structure determinations of protein complexes. Candidates with prior experience in structural biology or biophysics are preferred. Our group is part of the laboratory of Crystal and Structural Chemistry of the Bijvoet Center. We house a facility for mammalian protein expression and purification. We are fully equipped for crystallographic studies. Other groups in the Bijvoet Center include mass spectrometry/proteomics (Heck), NMR (Boelens and Baldus), modeling of protein complexes (Bonvin), membrane enzymology (Van Meer), chemical biology (Killian and Liskamp) and protein folding (Braakman). Together with the center for Utrecht Life Science (Medical sciences, Veterinary sciences, Biology, Pharmacy of the Utrecht University and the Hubrecht laboratory for developmental biology) the Bijvoet Center forms a strong and stimulating scientific environment. Terms of employment Post-doc positions: we offer a position 2 and for 3 years, full time (1 fte). Your performance will be evaluated before 1 year to decide on (intended) prolongation of the contract. Your salary, depending on experience and performance, amounts EUR 2,379 to maximally EUR 3,755 (salary scale 10) gross per month. PhD student positions: we offer positions for 4 years, full time (1 fte). Your performance will be evaluated before 1,5 year to decide on (intended) prolongation of the contract. Your salary amounts EUR 2,042 to maximally EUR 2,612 (salary scale PhD) gross per month. The salary is supplemented with a holiday bonus of 8% and an end?of?year bonus of 8,3% per year. In addition we offer: a pension scheme, a partially paid parental leave, flexible employment conditions in which you may trade salary for vacation days or vice versa. Conditions are based on the Collective Employment Agreement of the Dutch Universities. (see http://www.uu.nl/uupublish/homeuu/homeenglish/working/termsofemploymen/4467main.html ). For information please contact Piet Gros, [email protected]. Please send applications to [email protected]. Further information http://www.crystal.chem.uu.nl/ http://www.bijvoet-center.nl/
