GAP · Investigating the role of the intercrypt goblet cells in inflammatory bowel diseases.

The mucus layer produced by the goblet cells (GCs), provides the barrier between the microbiota and the intestine preventing the occurrence of the inflammation process. Indeed, alteration in microbiota towards mucus degrading bacteria, are often associated with impaired mucus barrier properties and inflammatory bowel diseases, such as ulcerative colitis (UC). Although, the exact mechanisms behind UC are not understood, defects in luminal compartmentalisation of bacteria by mucus could play a major role in this disease etiology. The recent identification of the intercrypt goblet cells (icGCs) population has improved the understanding and modified the model of the mucus layer formed on the epithelial surface. The icGCs secrete mucus that differs from mucus produced by crypt-residing GCs, and both are required to provide a protective mucus barrier function. Deficient intercrypt mucus secretion or reduced icGC numbers leads to disruption of the mucus layer with an impaired organization at the mucus surface which correlates with increased colitis susceptibility. However, the mechanisms behind icGC defects still remain unclear. In this project, I will combine both animal and human studies to decipher the molecular mechanisms behind the loss of icGCs that occurs during UC and elucidate to what extent a deviated microbiota is involved in their modulation. The data from the research programme will underpin the development of future therapeutic strategies to improve human health. The fellow has experience in microbiota research, metabolism and nutrition. With this fellowship, he will have the opportunity to develop skills in mucin biology, evaluation of the mucus properties and imaging experiments. This grant will enable the fellow to develop his current skill set to include methodologies and approaches so that the microbiota features can be placed within a new biological context.