The project is aimed at understanding protein evolution under several selection pressures. The enzymes responsible for resistance against β-lactam antibiotics, the β-lactamases (BLAs) can be inhibited with specific BLA inhibitors. Combinations of β-lactam antibiotics and BLA inhibitors are used to treat infections with resistant pathogens. In this project, the ability to evolve immunity against BLA inhibitors is studied to find combinations of inhibitors to which immunity cannot be evolved. The work is multidisciplinary, comprising mutagenesis, protein production, biophysical, biochemical and structural characterization of BLA variants, as well as genetics and biological assays in zebrafish embryos.
The Macromolecular Biochemistry group is part of the Leiden Institute of Chemistry. The research focus is on understanding enzymes and enzyme interactions at the atomic level. The group houses excellent facilities for protein production and biophysical characterization. The Institute has a large NMR facility, with spectrometers dedicated to protein NMR (600, 850 MHz). The BLA team consists of several PhD students and technicians and the group is highly international. This project is a collaboration with Profs. Meijer (Inst. Biology, zebrafish experiments), Bitter (Free University Amsterdam, genetics) and Perrakis (NL Cancer Inst., crystal structure determination). 

• Master degree in Biophysics, Biochemistry or Molecular Biology;
• Ability to work independently in several research groups;
• Team player with initiative;
• Experience with protein purification, enzyme kinetics, X-ray diffraction, protein NMR, or handling zebrafish embryos is considered an advantage

We offer a position for initially one year. After a positive evaluation of the progress of the thesis, personal capabilities and compatibility the appointment will be extended by a further three years. Salary range from € 2,222 to €2,840 gross per month (pay scale P in accordance with the Collective Labour Agreement for Dutch Universities).

Leiden University offers an attractive benefits package with additional holiday (8%) and end-of-year bonuses(8.3 %), training and career development and sabbatical leave. Our individual choices model gives you some freedom to assemble your own set of terms and conditions. Candidates from outside the Netherlands may be eligible for a substantial tax break. More at https://www.universiteitleiden.nl/en/working-at/job-application-procedure-and-employment-conditions.

All our PhD students are embedded in the Leiden University Graduate School of Science www.graduateschools.leidenuniv.nl. Our graduate school offers several PhD training courses at three levels: professional courses, skills training and personal effectiveness. In addition, advanced courses to deepen scientific knowledge are offered by the research school. 

Diversity
Leiden University is strongly committed to diversity within its community and especially welcomes applications from members of underrepresented groups.

Universiteit Leiden

Leiden is a typical university city, hosting the oldest university in the Netherlands (1575). The University permeates the local surroundings; University premises are scattered throughout the city, and the students who live and study in Leiden give the city its relaxed yet vibrant atmosphere.

Leiden University is one of Europe's foremost research universities. This prominent position gives our graduates a leading edge in applying for academic posts and for functions outside academia. More at https://www.universiteitleiden.nl/en/working-at.

https://www.universiteitleiden.nl/werken-bij

Faculty of Science

The Faculty of Science is a world-class faculty where staff and students work together in a dynamic international environment. It is a faculty where personal and academic development are top priorities. Our people are committed to expand fundamental knowledge by curiosity and to look beyond the borders of their own discipline; their aim is to benefit science, and to make a contribution to addressing the major societal challenges of the future.

The research carried out at the Faculty of Science is very diverse, ranging from mathematics, information science, astronomy, physics, chemistry and bio-pharmaceutical sciences to biology and environmental sciences. The research activities are organised in eight institutes. These institutes offer eight bachelor’s and twelve master’s programmes. The faculty has grown strongly in recent years and now has more than 1,300 staff and almost 4,000 students. We are located at the heart of Leiden’s Bio Science Park, one of Europe’s biggest science parks, where university and business life come together. 

https://www.universiteitleiden.nl/en/science