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Mucosal host-microbe interactions

Friday 29 January 2016

Mucosal host-microbe interactions
Karin Strijbis

Project
The microbiota of the gastrointestinal tract is essential for human health. When microbial imbalance occurs, local effects such as Inflammatory Bowel Disease (IBD) or systemic effects on the immune system or the brain can occur. In the healthy gut, luminal bacteria are separated from the epithelial lining by a mucus layer that consists of glycosylated proteins, IgA antibodies and host defense peptides. A dysfunctional mucus layer will lead to increased host-microbe contact and inflammation. Innate immune receptors that are expressed by intestinal epithelial cells and dendritic cells recognize bacterial ligands and mount pro- and anti-inflammatory immune responses. The aim of our research is to elucidate the functions of intestinal immune receptors and investigate the impact of gut microbiota on human health and disease. In this project we will determine the molecular mechanisms of mucosal host-microbe interactions, investigate receptor-ligand interactions, intracellular signaling, transcriptional reprogramming and secretion of cytokines. The results of the experiments may lead to the development of novel infection intervention and prevention methods such as vaccine development and better treatment of inflammation-associated pathobiology.

Techniques
 PCR, cloning, electrophoresis, sequence analysis, gene expression by quantitative real-time PCR, SDS-PAGE, Western blotting, (recombinant) protein expression and purification, site-specific labeling of proteins using sortase technology;
 Culture of aerobic, microaerophilic and anaerobic commensal and pathogenic bacteria and yeasts;
 Mammalian cell biology methods such as cell culture of epithelial cells or macrophages, infection assays, generation of cell lines using retro/lentiviral gene transduction, generation of knockout and genetically altered cell lines using CRISPR/Cas9 technology;
 Immunological techniques such as ELISA and FACS analysis;
 Advanced (confocal) microscopy, immunofluorescence, protein trafficking and colocalization with fluorescent biosensors, fluorescent commensal/pathogenic microbes, and live cell imaging.

Duration
9 months (6 months)

Contact
Dr. Karin Strijbis, Tel: 030 - 2534755, K.Strijbis@uu.nl