Job Sanquin Blood Supply Foundation (Sanquin) - Post-Doc, department of Autoimmune Diseases Research, Amsterdam

The main focus of the project will be the function of the non-protease domain of C1-inhibitor. The effects of C1-inhibitor on the interactions between neutrophils and endothelial cells will be studied in an in vitro endothelial cell system. Both plasma-derived C1-inhibitor and recombinant protein with variations in glycosylation patterns will be studied. In addition, the post-doc will be involved in the coordination of the translational research lines of C1-inhibitor both in our department and with the groups of our collaborators.

The integration of basic protein and cellular work with clinical applications is an ambitious and challenging project. We request an enthusiastic, highly motivated and ambitious post-doc with

• At least two years of post-doc experience;
• Expertise in protein chemistry and cell biology with solid practical skills;
• Experience in writing grant applications;
• Open and creative mind with good communicating skills;
• Good command of spoken and written English, command of spoken Dutch is welcome.

• Challenging project in a multi-disciplinary and enthusiastic team;
• Temporary postdoctoral position that may be extended to 5 years in total;
• Salary and conditions are conform CAO Sanquin.

The research group autoimmune diseases is part of the Department of Immunopathology. Our main interests focus on the development of autoimmune diseases, interactions of plasma proteins with dead cells and serine protease inhibitors, such as C1-inhibitor. Our laboratory has a long track record in C1-inhbitor research. This research combines fundamental structure-function studies and expression of recombinant C1-inhibitor with clinical applications of C1-inhibitor.

The department comprises 40-45 people (postdocs, PhD-students, undergraduate students and technicians) that all work on related research topics. The research is carried out within the context of the Landsteiner Laboratory of the Academic Medical Center of the University of Amsterdam. We have extensive collaborations with other groups outside Sanquin.

Background

C1-inhibitor is a heavily glycosylated plasma protease inhibitor belonging to the serpin family which is crucially involved in regulation of plasmatic cascade systems such as the complement and contact phase system. The activation of these systems leads to the generation of pro-inflammatory and vasoactive substances. The importance of C1-inhibitor is evidenced by patients suffering from hereditary angioedema (HAE). HAE patients have reduced levels of C1-inhibitor resulting in an inadequate control of the contact and the complement system leading to the formation potentially life threatening subcutaneous edema. In other inflammatory diseases, such as sepsis and ischemia-reperfusion injury in myocardial infarction C1-inhibitor also seems to play important regulatory roles as demonstrated in animal models and in human patients. Recently, it was suggested that the heavily glycosylated non-protease domain has anti-inflammatory effects independent of the protease inhibition domain via interference with selectins and neutrophil adhesion to endothelial cells and via binding to LPS. These results concur with our findings that C1-inhibitor can decrease neutrophil activation and modulate cytokine production in sepsis patients.

For further information, please contact Dr. Sacha Zeerleder, project leader (tel. +31(0)20-5123171, e-mail s.zeerleder@sanquin.nl), Dr. Diana Wouters, project leader (d.wouters@sanquin.nl) or Dr. S. Marieke van Ham, head of department (m.van.ham@sanquin.nl).