Postdoctoral position (2 years) available at Lund University, Sweden to study complement inhibitor Factor I in health and disease. The applicant will join an ongoing project in a dynamic group of prof Anna Blom group who focuses on complement and innate immunity. Applicants should be highly motivated, communicative and inventive and have a Ph.D. in biochemistry, molecular biology, immunology, or related discipline. Particularly valuable experience: molecular biology, protein expression and chemistry.
Applicants should submit by e-mail (anna.blom@med.lu.se) curriculum vitae including publication list and e-mail address of two references.
Position available immediately but can be postponed several months for a suitable candidate. Salary (tax-free stipend) approx 1600 euro/month.
www.demesta.com/annablomresearch/
The complement system not only protects from infections as part of innate immune system but also regulates acquired immunity and removes waste (immune complexes, apoptotic cells). On the other hand, excessive or misdirected complement activation contributes to pathogenesis of many inflammatory diseases.
Factor I (FI) is a relatively poorly studied multidomain plasma proteinase and complement inhibitor. FI degrades activated complement factors C4b and C3b only when they are bound to a cofactor protein. Degraded C4b/C3b are not able to propagate complement cascade but fragments of C3b have profound physiological effects on antibody production. FI is a heterodimer of a heavy (one FI-membrane attack complex (FIMAC) domain, one CD5 domain, two low-density lipoprotein receptor domains) and a light chain (serine proteinase) linked by a disulfide bond. There is no known inhibitor of this proteinase and its activity is regulated by a very narrow substrate specificity. Since FI is a major complement inhibitor it is important to understand molecular basis of its activity that will hopefully allow creation of a synthetic inhibitor to be used in order to control unwanted complement activation in many acute and chronic inflammatory diseases.
The project is focused on investigation of different FI mutants in relation to their expression, proteolytical processing, secretion, stability and functional activities. The amino acids that have been chosen for mutagenesis are predicted to be important for protein-protein interactions based on high quality 3D homology-based model or found in patients with FI defects. The expression and purification system is already established.
Selected recent publications from the group
Trouw L., Nilsson S., Goncalvez I., Landberg G. and Blom A. M. (2005) C4b-binding protein binds to necrotic cells and DNA, which limits DNA release and inhibits complement activation., J. Exp. Med., 201, 1937-1948.
Sjöberg A., Önnerfjord, P., Mörgelin, M., Heinegård, D. and Blom A. M. (2005) Extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q., J. Biol. Chem., 280, 32301-8.
Nilsson S. C., Karpman D., Vaziri-Sani F., Kristofferson A., Salomon R., Provot F., Fremeaux-Bacchi, Trouw L. A., and Blom A. M. (2006) A mutation in factor I that is associated with atypical hemolytic uremic syndrome does not affect factor I function in complement regulation., Molecular Immunology, in press
Organisation - Lund University
Division/Faculty/Department - Laboratory Medicine
Street - wallenberg Laboratory floor 4
City - Malmo
Postal Code - S-20502
Country - SWEDEN
E-Mail - anna.blom@med.lu.se
Website - www.demesta.com/annablomresearch/
Application Deadline - 30/01/2007
