Background

Due to antibiotic resistance, there is now great interest in the development of antibody-based therapies against bacterial infections, for instance via antibodies that boost the host immune system. To kill bacteria, antibodies should trigger activation of the complement cascade, which forms bactericidal Membrane Attack Complex (MAC) pores and strongly enhances phagocytosis. Although the power of complement could be exploited for antibody therapies, such developments are hampered by our limited insights into the mechanisms underlying antibody-dependent complement activation on bacteria. In this proposal, we will combine our function-driven approaches with B cell sequencing methods to identify antibodies against pathogenic E. coli strains with strong complement-activating potential.

The postdoctoral fellow will be tasked to set-up and perform yeast Fab display screening in my lab. He/she will travel to Boston (2 months) to get familiar with yeast display technologies in the laboratory of Dr. Brandon DeKosky, who developed a yeast display platform for large-scale interrogation of natively paired VH:VL antibody repertoires. In Utrecht, the postdoc will be tasked to generate yeast libraries from paired VH:VL amplicons (derived from B cells of patients infected with E. coli) by cloning and expression into Ig yeast display vectors. Postdoc will develop methods to select yeast cells that display bacterium specific antibodies using fluorescence-activated cell sorting (FACS). Sorted yeast populations will be characterized by next generation sequencing, and sequences will be mined to select interesting clones. Postdoc will develop transposon screening methods to identify bacterial antibody targets.

Responsibilities

• Drive and develop scientific projects focused on antibody discovery using yeast display
• Transfer yeast display technology from the lab of Dr. Brandon DeKosky to Utrecht
• Generate yeast Fab display libraries from B cells of infected patients
• Perform and optimize yeast display screening (FACS)
• Analyse next generation sequencing datasets
• Identify bacterial antibody targets using transposon mutagenesis
• Collaborate with other scientists (PhD students and technicians).

Qualification

The successful candidate should hold a PhD and strong knowledge in one or more of the following: molecular microbiology, antibody biology, yeast display. Candidate should have a track record of creativity in developing experimental strategies, experience with fluorescence-activated cell sorting (FACS), molecular biology in bacteria/yeast and high-throughput data analysis is highly desirable. Must be self-motivated and capable to work in autonomy, but also able to collaborate with other scientists in our team. Evidence of scientific accomplishment via peer-reviewed publications is required. Excellent written and verbal communication skills in English are essential. Candidates will be stimulated to write personal grants.

Experience / Skills

• PhD in microbiology, immunology or human antibody discovery
• Interest in human immunity against bacterial infections
• Experience of collaboration with biologists for solving concrete biological problems
• Experience in analyses of next generation sequencing
• Experience with flow cytometry-based cell sorting
• Experience working with yeast display technology is desirable
• Experience with molecular biology in bacteria is desirable

We believe in the power of a diverse team in which there is room for different skills, expertise, and social and cultural backgrounds. We invite you to respond to this vacancy.

The salary for this 36 - 36 function is still to be determined.

In addition, we offer an annual benefit of 8.3%, holiday allowance, travel expenses and career opportunities. The terms of employment are in accordance with the Cao University Medical Centers (UMC).

The ‘Bacterial Infections and Immunity’ laboratory of Prof. Suzan Rooijakkers is at the Department of Medical Microbiology, University Medical Center Utrecht located on the Utrecht Science Park (Uithof, The Netherlands). Our lab studies the molecular interplay between bacteria and the human immune system, with a strong focus on complement biology and antibodies.

http://www.evasionutrecht.nl/themes/suzan-rooijakkers-bacteria-complement/. 

The UMCU (10,000 employees) and Utrecht University (30,000 students) are located within one campus. The UMCU has a delegated responsibility for education in health care, medicine and biomedical sciences, and for medical research in synergy with the Utrecht University (UU), which ranks 6th on listings of top EU research facilities. The Department of Medical Microbiology is embedded in UMCU’s research program Infection and Immunity. This research program consists of 30 research groups and 180 PhD students. Rooijakkers is the head of the Bacterial Infections & Immunity research group.