Project Area B
B1 - Characterization of the interaction of luminal factors with the intestinal epithelium: Signaling pathways and effects on transport properties
Prof. Dr. Holger Martens, Institut für Veterinär-Physiologie, Freie Universität Berlin
The project investigates activation of mechanisms of epithelial cells by probiotics (E. faecium) or zinc, related to epithelial transport properties and integrity. It focuses on characterization of the functions of heat shock proteins and cytokines, which are released upon challenge by E. faecium, on intestinal transport and barrier. The possible involvement of toll-like receptors in the suggested signal cascade induced by E. faecium will be tested. The effects of zinc on the secretory capacity of the intestinal epithelium and its signalling pathways, on absorptive capacities, and its protective role against infections will be studied.
B2 - Paracellular intestinal barrier effects of probiotics and feed additives
Prof. Dr. Michael Fromm, Prof. Dr. Jörg-Dieter Schulzke, Charité – Universitätsmedizin Berlin
Paracellular permeability of the piglet intestine will be determined (i) by the tight junction meshwork, (ii) by apoptotic events, and (iii) by epithelial discontinuities under the influence of feed additives. First we will characterise abundance and distribution of tight junction components in the intestine, followed by experiments on barrier properties of ex vivo preparations from jejunum or colon of piglets with and without feed additives. Analysis will include molecular, electrophysiological, and fluorescence-microscopical techniques. Porcine cell culture models will serve to elucidate regulatory mechanisms of barrier modulation.
B3 - The effect of nutrition factors on miRNA and gene expression in the immune response of mesenteric lymph nodes in piglets during the weaning period
Dietary supplementation of probiotics as well as zinc is supposed to improve health in weaning piglets and to protect against infections. Our aim is to identify mechanisms contributing to expected improved defence as result of dietary supplementation. We will examine whole genome gene expression and study signalling pathways in the immune system in mesenteric lymph nodes in piglets untreated or treated with either Enterococcus faecium NCIMB 10415 or zinc. Our data will be analyzed together with data from other projects to find systems biological correlations between all parameters.
B4 - Role of intestinal luminal factors such as zinc and microbiota on regulating microRNAs and profiling of the downstream pathways
The objective is focused on the impact of luminal factors on intestinal microRNA (miRNA) response. Feed additives (e.g. zinc or probiotics) but also pathogens will be taken into consideration. The impact of intestinal miRNAs on corresponding targets and their role on optimal pathogen defence will be analysed using a primary porcine intestinal epithelial cell culture model. The resulting in vitro data will be verified within the later phase of the project using an in vivo model. This approach will contribute to a better understanding of regulating factors, and new local aspects may be provided for novel therapeutic strategies.
B5 - Bioavailability of zinc and other trace elements and their impact on genomic stability
Aim of the project is to assess the impact of zinc on genomic stability in different cell types of pig small intestine. Extent of oxidative DNA damage in the tissue due to different zinc levels will be performed in close cooperation with C3. Also, interactions with other trace elements will be investigated, both with respect to bioavailability and function in genomic stability. In parallel to the in vivo studies indicated above, mechanistic investigations will be conducted in an epithelial type cell line derived from pig small intestine; here, more detailed studies on DNA damage, DNA repair capacity, cell cycle control and gene expression profiles will be performed.
B8 - Effects of nutritional supplements on the porcine innate immune response to intestinal pathogens – infection models
Dr. Karsten Tedin, Institut für Mikrobiologie und Tierseuchen, Freie Universität Berlin
The aims of the project are to establish the roles of innate immune response effectors in the defense against bacterial pathogens in swine and determine whether the functions and activities of these effectors can be modulated by nutritional supplements. We will develop methods for the screening of components and/or activities of probiotic bacteria, which influence the innate immune system of swine in response to gastrointestinal pathogens. The effects of zinc supplementation on Peptidoglycan Recognition Protein (PGRP) expression and activities will also be examined, as well as immune cell functions during animal feeding trials.





