PhD candidate in Enzymatic synthesis of complex bacterial glycans

In the NWO-Vidi project 'Healthy sugars for a healthy gut', 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, combining the powers of synthetic chemistry, biochemistry and microbiology. One research area deals with synthetic method development and production of health-beneficial oligosaccharide structures. The other research area is dedicated to the investigation of bacterial protein glycosylation to the point where we can start exploiting it to generate novel antibacterial therapies.

We are looking for an enthusiastic and talented PhD candidate with:

• An MSc degree in molecular biology, biochemistry, biotechnology/bioengineering, or equivalent certification.
• Strong experimental background in molecular biology, synthetic biology, or metabolic engineering.
• Hands-on experience with expression and purification of (membrane) proteins and enzymes will be seen as a strong asset.
• Capacity to think analytically and creatively.
• High motivation in pursuing academic research.
• Ability to work in an international team and collaborate with several research centers in Europe in a streamlined and professional way.
• An integrative and cooperative personality with excellent communicative and social skills.
• Fluent proficiency in English – written and oral.

Bifidobacteria produce a unique extracellular sugarcoat, the glycocalyx, which is rich in exopolysaccharides. Exopolysaccharides (EPS) are associated with many human-host benefits, including immune signal modulation, anti-pathogen effects, and a healthy gut, but a clear understanding of which exopolysaccharides are responsible for which health effects is missing. Currently, the only method to obtain exopolysaccharides is through isolation from bacterial culture broths, resulting in low yields and often low purities of exopolysaccharide samples. This makes it challenging to directly prove structure-activity relationships related to the bifidobacterial beneficial effects.

The goal of this PhD project is to develop enzymatic synthesis methods to produce a variety of bifidobacterial exopolysaccharides. Enzymes from the predicted biosynthesis pathways will be expressed and their activity will be validated. Combinations of enzymes will be employed to produce EPS structures of different lengths and levels of complexity. Plasmid engineering will be performed towards microbial cell factories that produce EPS structures. In collaboration, the resulting EPS structures will be tested for their functional effects in intestinal model systems and lay the foundation to prove bifidobacterial health effects. This PhD project will be in close collaboration with a PhD project on the chemical synthesis of EPS structures within the same NWO-Vidi project, promoting an interdisciplinary approach to this synthetic challenge.

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.