Host institution: Quadram Institute Bioscience (UK)

Main supervisor: Prof. Nathalie Juge

Co-supervisor(s): Prof. Patrice Cani (Universite Catholique de Louvain, Belgium), Dr. Louise Vigsnaes (Glycom, Denmark)

PhD duration: 48 months

Desired start: September 2019

ESR3 PhD project:  Defining the molecular mechanisms underpinning host O-glycan recognition by gut bacteria

Background: The complex microbial community (microbiota) inhabiting the large intestine has a profound effect on health and physiology, providing benefits such as modulation of immune development, digestion of complex carbohydrates, and inhibition of pathogen colonization. However, abnormalities in microbiota composition (dysbiosis) have been implicated in several disease states. One major factor shaping the composition and physiology of the gut microbiota is the availability of dietary and host glycans into the intestine. In addition to carbohydrates from the diet, some gut bacteria have the ability to utilise host glycans such as human milk oligosaccharides (HMOs) (in infants) or host O-glycans present on mucins (in adults) as a source of nutrient.

Project description: The overall aim of the project is to gain mechanistic insights into the receptors involved in the interaction between bacteria/probiotics and host glycans. Specific objectives include 1/ to characterise the kinetics of interaction between major host O-glycan structures (mucin oligosaccharides, HMOs) and gut bacterial cell surface proteins (adhesins, lectins) and 2/ unravel the metabolic pathways involved in mucin/HMO glycan degradation/utilisation by major gut symbionts. During your PhD project you will receive training and acquire expertise molecular microbiology (anaerobic growth cultures, cloning and heterologous expression, mutagenesis); recombinant protein purification; in vitro binding assays such as Surface Plasmon Resonance (SPR); Isothermal titration calorimetry (ITC); in vitro activity assays and carbohydrate analysis (Nuclear Magnetic Resonance (1H-NMR) or High-performance anion-exchange chromatography (HPAEC), metabolomics. Training will embrace research practice and theory, management, communication (to scientific and lay audiences), intellectual property, teamwork and technical writing. The student will present his/her work to internal seminars and to relevant International meetings. The possible commercial issues relating to the impact of this research on human health will be highlighted and the student will be encouraged to participate into outreach activities.

Planned secondments: 1) Universite Catholique de Louvain (3 months) metabolite analysis 2) Company Glycom (3 months) synthesis of novel oligosaccharides.

Requirements for all candidates: In accordance with the very strict EC Marie Skłodowska Curie Actions (MSCA) Sweet Crosstalk ITN rules you must meet the following two eligibility criteria for your ESR/PhD position(s) of interest (so, please do not respond if you are not eligible):

Eligibility criteria 1: Candidates did not reside or carry out their main activity (e.g. reside, work, studies) in the country of the PhD host institution for more than 12 months during the 3 years immediately prior to project’s application deadline (time spent as part of a procedure for obtaining refugee status under the Geneva Convention, compulsory national service and/or short stays such as holidays are not taken into account).

Eligibility criteria 2: Candidates are in the first four years of their research careers upon the starting date of their appointment to an ESR/PhD position (full-time equivalent research experience, measured from the date when a researcher obtained the degree entitling him or her to embark on a doctorate) and have not been awarded a doctoral (PhD) degree.

Please read the requirements for candidates and application procedure details at: https://sweetcrosstalk.eu/recruitment/

For more information on this ESR vacancy contact: nathalie.juge@quadram.ac.uk

This is one of 15 Marie Curie Early Stage Researcher (PhD) positions within the Sweet Crosstalk Network on understanding the molecular-level role of glycans at the human mucosa–microbiota interface

Sweet Crosstalk is a multidisciplinary European Training Network built to address the challenge of understanding, at a molecular level, how glycans are involved at the human mucosa–microbiota interface, and how this correlates with human well-being. The research strategy of the Sweet Crosstalk programme focuses on optimal synergy between chemistry and biology. In the network the expertise ranges from chemical synthesis, biochemistry, structural biology to microbiology and cell biology.

Read more at https://sweetcrosstalk.eu/