PhD position Biochemical approaches to study adhesin glycosylation

In the ERC-StG project STICKY SUGARS, a fully funded 4-year PhD position is available in the Chemical Glycobiology group of Prof. Marthe Walvoort, in the division of Chemical Biology at the Stratingh Institute for Chemistry, University of Groningen. Research in the Walvoort group is dedicated to understanding the structure-activity relation of carbohydrates. One area deals with the investigation of bacterial protein glycosylation to the point where we can start exploiting it to generate novel antibacterial therapies. The other area is dedicated to synthetic method development and production of interesting oligosaccharide structures.

Research project:
With bacteria increasingly resistant to current antibiotics, new strategies to fight infection are needed. Bacterial adhesin proteins, which play an important role in the establishment of infection, appear to be promising targets for novel therapies. Adhesins enable the first contact between bacteria and host cells. We know that some adhesins are modified with highly unique sugars that are important for adhesin stability and adherence. However, we do not know how widespread this modification is among bacterial strains, and whether it constitutes a good target for antibacterial strategies. A lack of suitable methods for the detection of bacterial adhesin sugars has impeded the detailed study of these sugars, blocking further efforts to develop antibacterial strategies against bacterial adhesin sugars.

The goal of this PhD project is to develop methods to visualize glycosylation directly on adhesin proteins to increase our understanding of adhesin sugars, in terms of timing and prevalence of the modification, which is crucial information to start targeting adhesin sugars. Using enzyme engineering, a set of specific glycosyl transferases will be generated which will be used to develop a specific labelling method for adhesin glycosylation. In addition, labelling methods based on lectins and antibodies will be explored. Subsequently, the novel detection methods will be applied in in vitro (screening) assays on isolated proteins and directly on bacterial cells (lab strains and clinical isolates) under varying conditions. By visualizing adhesin sugars directly on bacteria, we can observe their response to antibacterial treatments and pave the way toward clinical applications in the future.

Organisation
Founded in 1614, the University of Groningen University of Groningen (https://www.rug.nl ) enjoys an international reputation as a dynamic and innovative centre of higher education offering high-quality teaching and research. Flexible study programmes and academic career opportunities in a wide variety of disciplines encourage the 36,000 students and researchers alike to develop their own individual talents. As one of the best research universities in Europe, the University of Groningen has joined forces with other top universities and networks worldwide to become a truly global centre of knowledge.

The Stratingh Institute for Chemistry is a research institute at the Faculty of Science and Engineering of the University of Groningen. With 18 principal investigators, the Stratingh Institutes performs excellent research and teaching in molecular and supramolecular chemistry. Core activities in the chemical sciences such as bio-organic chemistry, organic chemistry, molecular inorganic chemistry and molecular materials chemistry are embedded in the institute. The research programme is focussed on synthesis, catalysis, functional materials, bio-organic chemistry/chemical biology and systems chemistry/complex molecular systems.

We are looking for an ambitious, motivated, creative and practically skillful student with an MSc degree in Biochemistry / Microbiology / (Molecular) Life Sciences, or equivalent. A strong background in protein expression and enzyme engineering is a prerequisite. An interest in chemical biology, and multidisciplinary research is desired. Strong verbal and written communication skills (in English) are required.

We offer you in accordance with the Collective Labour Agreement for Dutch Universities:

• a full-time (1.0 FTE) position for four years
• a salary of € 2,541 gross per month in the first year, up to a maximum of € 3,247 gross per month in the fourth and final year for a full-time working week
• a holiday allowance of 8% gross annual income
• an 8.3% year-end bonus
• a position for four years; first, you will get a temporary position of one year with the option of renewal for another three years; extension of the contract is contingent on sufficient progress in the first year so that successful completion of the PhD thesis within the contract period is to be expected.

A PhD training programme is part of the agreement and the candidate will be enrolled in the Graduate School of the Faculty of Science and Engineering.

The conditions of employment: https://www.rug.nl/about-us/work-with-us/

The starting date is September 2023, however, there is considerable flexibility in the starting date.