The mucus barrier, antimicrobial proteins and IgA operate together to confine symbiotic bacteria towards the outer mucus layer and protect the epithelial surface by limiting bacterial penetration. This homeostatic interaction between mucus and gut commensals is critical to maintain gut health. Intestinal pathogens have evolved strategies for subverting and evading these barriers to access host tissues. By contrast, there is currently very limited knowledge of the mechanisms resident members of the intestinal microbiota interact with components of the mucus barrier.
Mucus-binding proteins (MUBs) are a class of cell-surface adhesins found in Gram-positive gut symbionts, shown to mediate interaction of bacteria to mucus. Building on our extensive preliminary data on the structural and biochemical properties of MUB, the purpose of this study is to determine the molecular and cellular basis of MUB interactions with receptors of the mucus layer, mucins glycans and mucosal antibodies and assess the potential of the impact of MUBs and IgA interaction on bacteria adhesion to mucus and IgA effector function, providing mechanistic insights into the regulation of gut microbiota homeostasis. Understanding the molecular basis of these processes will help understand how some bacteria strains exert intestinal health protection and devise intervention strategies to reinforce gut health.
This interdisciplinary project will benefit from the established international network of collaborations of the Lab in this area of research. In addition to the proposed experimental work, the post-holder will contribute to the research by interacting with research scientists and PhD students in the Group and by following up existing collaborations with scientists on the Norwich Research Park and with external collaborators, writing-up reports and publications, presenting at relevant meetings and Conferences. The post-holder will be encouraged to present his/her results to the general public by joining IFR-led Public Engagement activities. In addition, he/she will benefit from regular BBRSC-sponsored training courses in career development and transferable skills.
Key relationships
The post-holder will work in the Gut Health and Food Safety Programme and will be line-managed by Dr Nathalie Juge. He/she will work closely with PhD students and with research assistants , Louise Tailford and Donald MacKenzie in the Juge Group. The successful candidate will be expected to present work at internal Lab Programme and meetings and at Conferences.
Main Activities & Responsibilities
- MUB ligand characterisation in vitro and binding kinetics & thermodynamics
- Lactobacillus reuteri binding specificity to cell lines and in vitro tissue culture models
- MUB binding specificity to cell lines and host tissues
- MUB and MUB repeat purification and characterisation
- Writing-up reports, publications, presentations
- Contribute to Lab supervision
Education & Qualifications
- PhD biochemistry/molecular microbiology/cell biology or equivalent experience
- BSc in Biological Sciences
- Expertise in glycobiology
- Expertise in gut microbiology
Read Further about the position