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GRK 1482 Jahrbuch 2011-2014

JUNIOR PRINCIPAL INVESTIGATORS GRK Annual Report 2011-2014 | Page 33 Education / Degrees 1993 - 1998 Biology, Heinrich Heine-Universität Düsseldorf, Germany 1998 Diploma in Biology, Heinrich Heine-Universität Düsseldorf, Germany 2002 PhD in Biology (Dr. rer. nat.), Institute of Genetics, Heinrich-Heine-Universtität Düsseldorf, Germany Positions held 2002 - 2004 Postdoctoral fellow, Institute of Neurogenetics, Ludwig-Maximilian Universität, München, Germany 2004 to date Research associate and C. elegans-group leader, Lehrstuhl für Ernährungsphysiologie, Technische Universität München Research Interests and Achievements The focus of Britta Spanier´s research group lays on the exploration of the physiological and metabolic role of peptide transporters in Caenorhabditis elegans (round worm) and mammals. In all living organisms the peptide transporter PEPT1 mediates the efficient uptake of amino acids from pro- tein digestion as di- and tripeptides. Its function is coupled to the trans- membrane proton gradient which provides a powerful driving force for the proton-coupled transport of small peptides into enterocytes. To avoid acidification of the cells, Na+/H+ exchangers (NHE3/NHX-2) mediate the efflux of protons in exchange with extracellular Na+ ions. We discovered that the depletion of PEPT-1 initiates dramatic metabolic shifts in lipid sto- rage and fatty acid homeostasis of C. elegans resulting in the most obese worm described so far. These results are basis for further studies initiated in the GRK. In the first project, in which the impact of a high-fat diet on PEPT1- depleted mice was analysed, it was found that, in contrast to the worms, the loss of PEPT1 protects the mice against diet induced obesity. This is based on a maldigestion/-absorption of nutrients resulting in a high energy excre- tion which is driven by an absent adaptation of the gut architecture to the diet. Currently, we focus on the impact of the pHi regulation by PEPT1 and NHE3/NHX-2 on the action of the dual oxidase DUOX1/2 as potent H2O2 producer and key modulator in the intestinal pathogens defence. Dr. Britta Spanier Technische Universität München Physiology of Human Nutrition Gregor-Mendel-Str. 2, D-85350 Freising-Weihenstephan Selected Publications Kolodziejczak D, Spanier B, Pais R, Kraiczy J, Stelzl T, Gedrich K, Scherling C, Zietek T, Daniel H. Mice lacking the intestinal peptide transpor- ter display reduced energy intake and a subtle maldigestion/-absorption that protects them from diet-induced obesity. Am J Physiol Gastro- intest Liver Physiol. 2013, PMID 23494121. Grünz G, Haas K, Soukup S, Klingenspor M, Kulling SE, Daniel H, Spanier B. Structural features and bioavailability of four flavonoids and their im- plications for lifespan-extending and antioxidant actions in C. elegans. Mechanisms of Ageing and Development. 2012, 133:1-10. Benner J, Daniel H, Spanier B. A glutathione per- oxidase, intracellular peptidases and the TOR complexes regulate peptide transporter PEPT-1 in C. elegans. PLoS One. 2011, 6: e25624. Spanier B, Lasch K, Marsch S, Benner J, Liao W, Hu H, Kienberger H, Eisenreich W, Daniel H. How the intestinal peptide transporter contributes to an obesity phenotype in Caenorhabditis elegans. PLoS One. 2009, 4: e6279. Research Goals Understanding the interplay of pH-driven nutrient transport processes and sodium- proton exchangers with pathogen defence in the intestine Find regulators and interaction partners for the transcriptional and (post-) translational expression control of the intestinal peptide transporter PEPT1 Analyse the cellular adaptations and metabolic processes in various organisms in concert with PEPT-1 function