Members

Dr. Buettner studied Food Chemistry, subsequently completed her PhD in the field of aroma research, and was awarded her professorship in the field of flavor research. Her work has demonstrated the importance of the combined effects of the food and matrix composition, saliva, mucosa, mastication and swallowing on flavor release and perception. She has identified new odorous compounds with a special focus on citrus and other food materials and has worked on structure-odor relationships. Recent work additionally addresses packaged foods and products of daily use in relation to their chemosensorially active constituents. Some of her experimental methods include chemical trace analysis, quantification via stable isotope dilution analysis, monitoring of physiological processes, psychophysical measurements of sensory data, and determination of chemosensorially active and volatile compounds as well as their metabolites in vivo. In current studies at the University of Erlangen and Fraunhofer IVV, Freising, Dr. Buettner has broadened her research interests to include the field of volatiles and chemosensorially active compounds in the physiological context, with monitoring of uptake, distribution and biotransformation of odorants, as well as neoformation of metabolites from non-volatile food ingredients in vivo, as well as further physiological impact of such derivatives in humans. With her work she contributes with her team to the research aims of ZIEL regarding chemo-sensory and behavioral aspects in human nutrition, as well as biotransformatory processes in vivo.

The main focus of our research is the study of intestinal microbiomes (the communities of microorganisms, their genomes, and surrounding environmental factors in the gut). Because intestinal microorganisms have a major impact on the physiology of their host, it is important to investigate and understand their diversity and functions. We focus primarily on the human, pig, and mouse gut microbiomes because of their relevance for health-related issues. In particular, we are interested in describing the taxonomic diversity and evolution of gut bacteria thanks to the use of culture-based and sequencing approaches. Within ZIEL, research efforts are dedicated to the development of sequencing approaches for assessment of complex microbial communities. Importantly, these molecular approaches are coupled with classical bacteriology for creation and utilization of bacterial strain collections from the mouse and pig intestine. These collections are screened for specific functions, e.g. metabolism of cholesterol-derived compounds, and used for the establishment of minimal microbiomes to study microbe-microbe and microbe-host interactions in vitro (using continuous culture) and in vivo (using gnotobiology). For instance, we are interested in clarifying the role of secondary bile acids production in animal models of chronic intestinal inflammation and colorectal cancer provided by other ZIEL members.

The chair of Food Chemistry and Molecular Sensory Science comprises international research teams with several focus areas. Working together with the different working groups of ZIEL, our current research addresses:
    • the structural decoding and functional reconstruction of chemosensory signatures of foods and beverages (Sensomics),
    • an activity-guided discovery of bioactive natural products in foods and complex biological systems (Bioactives),
    • the human metabolism of bio-functional food ingredients using metabolomics profiling and a molecular definition of nutritive biomarker profiles (Nutritional Metabolomics), and
    • the molecular and functional mapping of the metabolic response of food plants on abiotic and biotic stress conditions (Phytometabolomics).
The unique methodology of Sensomics combines state-of-the-art natural product analytics, human psychophysical techniques, and bioinformatics tools with our unequaled expertise in the field of food chemistry and allows for a sustained scientific competitive advantage. Sensomics is considered the cutting-edge science concept to molecularize flavor entities of nature, thus setting the ground for a new quality of knowledge-based flavor optimization leading the way to creating real culinary authenticity.
Our bioactives group aims at discovering natural products with diverse, but specific bioactivities. These include anti-oxidative, antidiarrheal, antiviral, anti-diabetic, and anti-carcinogenic compounds, mycotoxins, and bacterial toxins in food products and plant materials. They are analyzed by means of bioassay-guided fractionation using cellular and/or chemical assays in combination with instrumental analysis (LC-TOF-MS, 1D-/2D-NMR, CD etc.). Thereafter, the bioactives are quantified by means of LC-MS/MS or qNMR and their metabolic fate is studied in intervention studies.
As the metabolome cannot be computed from the genome, the goal of our nutritional metabolomics group is to monitor and quantify low molecular weight molecules produced by active cells under different conditions and times in their life cycles. Due to the enormous analytical progress made in recent years, metabolite profiling by means of state-of-the-art liquid chromatography - mass spectrometry (HILIC-MS/MS, UPLC-TOF-MS) has reached a high level of sensitivity, increasing metabolite coverage and achieving a high sample throughput. As metabolomics is a data-driven technology, the transformation of raw data into information suitable for biological interpretation is achieved by the implementation of sophisticated bioinformatics tools adapted to our field of research.
The science-driven breeding of stress-tolerant cultivated plants will allow for a reduction in harvest losses and prevent the undesirable decrease in quality attributes following herbal stress response. It requires a new quality of knowledge on molecular markers associated with relevant agronomic traits, on quantitative metabolic plant responses to stress challenges, and on the mechanisms controlling their biosynthetic pathways. Our phytometabolomics research group develops and applies mass spectrometry-based techniques of metabolomics and proteomics to quantitatively assess key metabolome alterations in plant-derived foods induced by biotic stress challenges (bacteria, fungi) as well as abiotic stress conditions, e.g. water stress, light stress, and mechanical stress.

Lainer, J.§; Dawid, C. §; Dunkel, A.; Gläser, P.; Wittl, S.; Hofmann, T. Characterization of Bitter-Tasting Oxylipins in Poppy Seeds (Papaver somniferum L.). J. Agric. Food Chem. 2020, DOI: 10.1021/acs.jafc.9b06655.

Baumann, T.; Dunkel, A.; Schmid, C.; Schmitt, S.; Hiltensperger, M.; Lohr, K.;  Laketa, V.; Donakonda, S.; Ahting, U.; Lorenz-Depiereux, B.; Heil, J., Schredelseker, J.; Simeoni, L.; Fecher, C.; Körber, N.; Bauer, T.; Hüser, N.; Hartmann, D.; Laschinger, M.; Eyerich, K.; Eyerich, S.; Anton,  M.; Streeter, M.; Wang, T.; Schraven, B.; Spiegel, D.; Assaad, F.;  Misgeld, T.; Zischka, H.; Murray, P.; Heine, A.; Korn, T.; Dawid, C.; Hofmann, T.;  Knolle, P.A.; Höchst, B. Regulatory myeloid cells paralyze T cell immunity through cell-cell transfer of the metabolite methylglyoxal. Nature Immunaology 2020, 21(5), 555–566.

Dawid, C.; Hille, K. Functional metabolomics—a useful tool to characterize stress-induced metabolome alterations opening new avenues towards tailoring food crop quality. Agronomy 2018, 8, 138, DOI:10.20944/preprints201807.0052.v1.

Kutschera, A.§; Dawid, C.§; Gisch, N.; Schmid, C.; Raasch, L.; Gerster, T.; Schäffer, M.; Smakowska-Luzan, E; Belkhadir, Y.; Vlot, C.; Chandler, C. E.; Schellenberger, R.; Schwudke, D.; Ernst, R.; Dorey, S.; Hückelhoven, R.; Hofmann, T.; Ranf, S. Bacterial medium-chain 3-hydroxy fatty acid metabolites trigger immunity in Arabidopsis plants. Science 2019, 364(6436), 178–181.

Our research is focused on fractionizing processes for plant raw material in order to isolate functional protein ingredients and nutritional fibers for the use in human nutrition and technical applications. The resulting lipids, proteins, soluble and insoluble dietary fibers are modified thermally, enzymatically, chemically and mechanically to customize functional properties such as solubility, water and oil binding capacity, gel formation, and emulsifying capacity. In the frame of ZIEL nutritional aspects such as bile acid binding and influence of nutritional fibers on human intestine are investigated.

The second research area is focused on the processing of new food matrices and the development of model recipes in order to modify the texture and nutritional properties of foods. The used equipment and facilities are part of the ZIEL-Core-Facility “Food Processing”. The laboratories and machines are designed for the production of food samples for human studies.

The ZIEL-Core-Facility enables the production of a wide range of foods covering meat/sausage products, fruit/vegetables, bakery goods, pasta, and confectionery. Research is carried out concerning stabilization of textures and oxidation-sensitive ingredients, and sensorial optimization of food e.g. by fermentation. The influence of innovative processing technologies on quality parameters of food is investigated. Technologies such as electromagnetic fields for gentle pasteurization and sterilization and high-moisture-extrusion-cooking for plant based textures in meat alternatives are studied.

Publications

Meinlschmidt P., Brode V., Sevenich R, Ueberhame E., Schweiggert-Weisz U., Lehmann J., Rauh C., Knorr D., Eisner P. (2016)
High pressure processing assisted enzymatic hydrolysis – An innovative approach for the reduction of soy immunoreactivity, Innovative Food Science and Emerging Technologies, doi: 10.1016/j.ifset.2016.06.022

Meinlschmidt P., Ueberham E., Lehmann J, Schweiggert-Weisz U., Eisner P. (2016)
Immunoreactivity, sensory and physicochemical properties of fermented soy protein isolate.
Food Chemistry, Vol.  205, pp. 229-238.

Zacherl C., Eisner P., Engel K.-H. (2011)
In-vitro model to correlate viscosity and bile acid-binding capacity of digested water-soluble and insoluble dietary fibres.
Food Chemistry, Vol. 126, pp. 423-428.

Prof. Kurt Gedrich studied Home Economics at the Technical University of Munich (TUM). After obtaining his degree in 1993, he focused on econometric analyses of food consumption and nutrient intakes and received a Ph.D. degree in Nutrition Economics in 1996. Until 2011, he was a group leader at TUM’s department of marketing and consumer research, particularly dealing with food consumption in various population groups from positive as well as normative perspectives. With increasing interest in determinants of food choice he completed his postdoctoral thesis in 2005 and received the university teaching credentials for Nutritional Behavior in 2006. In 2012, he moved closer to the core of nutritional science and joint the team at TUM’s chair of Nutrition Physiology where he formed and led the personalized nutrition group. In 2019, he became a member of the ZIEL - Institute for Food & Health and head of the Research Group Public Health Nutrition.

‘You are what you eat’. While this phrase is certainly not to be taken literally, decisions about what and how much to eat have a strong influence on health and well-being. How do we decide what to eat and what to avoid? The senses of smell and taste are the most important modalities in this decision. Our research aims at understanding how such chemosensory information is processed by the brain to guide decision-making and how physiology and metabolic needs such as hunger influence neuronal processes and cognitive function. To this aim, we use an interdisciplinary approach combining molecular biology, genetics and genomics in model organisms such as Drosophila melanogaster, electrophysiology, in vivo multiphoton functional imaging and state-of-the-art behavioral analysis.

As a member of ZIEL, we strive to translate our findings in model organisms to humans, their physiology and particular needs. To this end, we benefit from the expertise at ZIEL and access to the ZIEL core facility for human cohort studies. Furthermore, we are interested in understanding the interplay between the gut microbiome, neural processing and food decisions. To this end, we interact with ZIEL’s microbiome experts and take advantage of the ZIEL microbiome core facility. Ultimately, joining fundamental research on the nervous system with ZIEL’s core strengths will help us decipher how brain and body interact to maintain long-term health and well-being.

Publications with relation to ZIEL
Hussain A*, Zhang M*, Üçpunar HK, Svensson T, Quillery E, Gompel N, Ignell R, Grunwald Kadow IC (2016). Ionotropic chemosensory receptors mediate the taste and smell of polyamines. PLoS Biol 14:e1002454. doi:10.1371
* equal contribution

Hussain A*, Üçpunar HK*, Zhang M, Loschek LF, Grunwald Kadow IC (2016). Neuropeptides modulate female chemosensory processing upon mating in Drosophila.
PLoS Biol 14:e1002455. doi: 10.1371
* equal contribution

Lewis L, Siju KP, Aso Y, Friedrich AB, Bulteel AJB, Rubin GM, Grunwald Kadow IC (2015). A higher brain circuit for immediate integration of conflicting sensory information in Drosophila. Curr Biol PMID: 26299514, doi: 10.1016/j.cub.2015.07.015

Research Sketch
The main areas of research are dedicated to the understanding of gut health and the pathogenesis of inflammation-related chronic disorders such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Compelling research over the past decade identified a fundamental role of the intestinal microbiome in human health and together with nutrition, the intestinal microbiome represents a prime environmental factor and plays a pivotal role in the development of these complex pathologies. At the level of mechanistic understanding, the molecular integration of pleiotropic signals coming from the complex and dynamically changing gut luminal ecosystem is one the biggest challenges in this field. We hypothesize that the intestinal epithelium provides a dynamic interface to sense the luminal milieu, especially microbial factors using mechanisms that implement pattern recognition receptors and cell stress responses (unfolded protein responses; UPR). We apply gnotobiotic studies in germ-free models to better understand the functional role of dysbiosis as a disease-conditioning mechanism for the development of inflammatory bowel diseases (IBD) and colorectal cancer (CRC). In this context, we generated a variety of novel tissue-specific mouse models and identified an essential role of unfolded protein responses (UPR) in the regulation of gut homeostasis. At ZIEL, we translate the fundamental knowledge of mechanistic studies into a human context by implementing fecal microbiota from human in germ-free models. We also perform human intervention studies to understand the role of nutrition on microbiome signatures in healthy and diseased human populations, e.g. formula food in infants or iron therapy in IBD patients. In addition, we follow large prospective cohort studies (e.g. KORA) to define the microbiome signatures in populations at the transition between health and disease.

Publications:
Schaubeck M, Clavel T, Calasan J, Lagkouvardos I, Haange SB, Jehmlich N, Basic M, Dupont A, Hornef M, Bergen MV, Bleich A, Haller D. Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence. Gut 2016 Feb;65(2):225-37. doi: 10.1136/gutjnl-2015-309333

 Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker A, Lucio M, Michalke B, Schmitt-Kopplin P, Fedorak R, Haller D. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 2016 Feb 4. pii: gutjnl-2015-3099408.

Berger E, Rath E, Yuan D, Waldschmitt N, Khaloian S, Allgäuer M, Staszewski O, Lobner EM, Schöttl T, Giesbertz P, Coleman OI, Prinz M, Weber A, Gerhard M, Klingenspor M, Janssen K-P, Heikenwälder M, Haller D. Mitochondrial function controls intestinal epithelial stemness and Proliferation. Nat Commun. 2016 Oct 27;7:13171

The Chair of Molecular Nutritional Medicine is dedicated towards the study of energy balance regulation, thermogenesis, and adipose tissue biology. To address our research questions we study the integrative physiology of energy metabolism from the systemic to the cellular and mitochondrial level. Adipose tissues form a highly heterogeneous and plastic organ with essential impact on the regulation of energy flux. Fat cells (adipocytes) not only represent the major energy depots of the body but also secrete hormones (adipokines) regulating hunger and satiety in the brain and metabolic fuel partitioning in peripheral high metabolic rate organs. Moreover, adipocytes acquire contrasting metabolic properties: white adipocytes are specialized in fat storage, while brown adipocytes dissipate food energy as heat. A novel type of brown-like adipocyte, known as beige or brite (brown-in-white), can be found in white adipose tissues.

Adult humans have metabolically active brown / brite adipocytes, but the developmental origin and physiological function of these cells remains elusive. The abundance and metabolic activity of these cells decreases with age and with the progression of metabolic disease (obesity, diabetes, cachexia). Recruitment and activation of brown / brite adipocytes in humans is associated with beneficial metabolic effects. Genes, epigenetics, nutrition and environment impact the abundance of brown and brite adipocytes.

Within the framework of ZIEL our interdisciplinary research revealed large individual variation in the amount and activity of brown fat between subjects. We now aim to identify the causes and consequences of high brown fat mass and activity in humans. On the mechanistic level, we investigate the nutritional regulation and the endocrine / paracrine signals triggering recruitment and activation of human brown and brite adipocytes. On the physiological level we study the function of thermogenic human adipocytes for food intake and energy expenditure. This will elucidate the role of heterogeneity and plasticity of the adipose organ in the etiology of metabolic diseases.

Publications:
Gerngroß C, Schretter J, Klingenspor M, Schwaiger M, Fromme T. Active brown fat during 18FDG-PET/CT imaging defines a patient group with characteristic traits and an increased probability of brown fat redetection. J Nucl Med. 2017 Jan 19, in press.

Kless C, Rink N, Rozman J, Klingenspor M. Proximate causes for diet-induced obesity in laboratory mice: a case study. Eur J Clin Nutr. 2017 Feb 1, in press

Kübeck R, Bonet-Ripoll C, Hoffmann C, Walker A, Müller VM, Schüppel VL, Lagkouvardos I, Scholz B, Engel KH, Daniel H, Schmitt-Kopplin P, Haller D, Clavel T, Klingenspor M. Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol Metab. 2016 Oct 13; 5(12):1162-1174.

Food and bioprocess engineering interlinks the basics of natural sciences and the fundamentals of process engineering. Thereby, all processes involved in the conversion of materials of animal and plant origin to food products are covered. We investigate physico-chemical and techno-functional properties of proteins and polysaccharides in relation to their molecular structure and in dependence of process conditions. Thereby, we aim at achieving a scientific understanding of the behaviour of complex substrates, single components as well as their versatile interactions with regard to processes. Emphasis is put on food quality and safety, technologically and nutrition-physiologically innovative as well AS efficient applications of raw materials and processes. Model systems serve as basis for the deduction of generic scientific understanding. This turns into research on specific food systems, allowing transfer of knowledge to final industrial applications. Our research focuses on four thematic areas, which provide manifold opportunities with regard to nutrition-technology-related collaborations within ZIEL:

• Fractionation and concentration of complex food systems by membrane separation technologies (MF/UF/NF/RO), membrane adsorption chromatography and centrifugal separation techniques.

• Structure formation and biophysical characterisation in terms of gels, emulsions and foams. This includes the deliberate modification of substrate properties and functionalities via pre-treatment and processing by ultrahigh pressure, thermal and/or mechanical technologies. We develop specific carrier systems (microcapsules, aerogels) and coatings for the preservation and targeted release of physiologically effective substances.

• Bioprocess engineering, aseptic processing and drying techniques (freeze drying, vacuum drying, microwave assisted vacuum/freeze drying).

• Enzymatic processes in the context of hydrolysis and fractionation of functional peptides.

Publications
Cheison, S. C.; Kulozik, U.: Impact of the environmental conditions and substrate pre-treatment on whey protein hydrolysis: A review. Critical Reviews in Food Science and Nutrition, 2017, 57, 2, 418-453.

Würth, R.; Lagkouvardos, I.; Clavel, T.; Wilke, J.; Foerst, P.; Kulozik, U.; Haller, D.; Hörmannsperger, G.: Physiological relevance of food grade microcapsules: Impact of milk protein based microcapsules on inflammation in mouse models for inflammatory bowel diseases. Molecular Nutrition & Food Research, 2015, 59, 1629–1634.

Würth, R.; Hörmannsperger, G.; Wilke, J.; Foerst, P.; Haller, D.; Kulozik, U.: Protective effect of milk protein based microencapsulation on bacterial survival in simulated gastric juice versus the murine gastrointestinal system. Journal of Functional Foods, 2015, 15, 116-125.

Research at the Chair of Microbial Ecology

First, current molecular genetics research concentrates on the molecular ecology of the food borne pathogen Escherichia coli (EHEC) which is one of the most dangerous foodborne pathogens leading to a significant number of lethal infections. Gene expression is analyzed using New Generation Sequencing technologies. Especially, we established translatomics (RIBOseq) at TUM which determines ribosome coverage and, thus, translation of RNA species. A variety of food relevant conditions is under investigation. Besides the annotated genes our major interest is focused on hitherto unknown genes. We have now evidence for the presence of more that 500 small intergenic protein coding open reading frames, more than 300 novel non-coding RNA and many protein coding reading frames completely embedded in antisense in annotated EHEC genes. The conditions under which these genes are expressed as well as their potential functions are of interest.

This work is relevant for the ZIEL food safety research. Furthermore, the RIBOseq technology adds another layer of information to gene expression in bacteria and is now being adapted to well-defined intestinal microbiota in the ZIEL Microbiome core facility in order to understand gene expression in the mouse gut.

Second, a research group investigates the presence of food borne microorganisms as well as their amazing biodiversity, including hundreds of novel, cultivable genera and species. The focus is on raw milk as well as milk products. Some of these microbes produce heat stable enzymes which have an economically significant spoilage potential. Detection methods for these peptidase producing bacteria as well as the molecular basis of enzyme production and the genetics of its regulation is in the focus of our research.

This work is relevant for the ZIEL food hygiene research. Furthermore, the food microbiome associated with certain food stuff is largely unexplored and its potential impact on the consumer is completely unknown.

Publikationen
Landstorfer R, Simon S, Schober S, Keim D, Scherer S, Neuhaus K (2014) Comparison of strand-specific transcriptomes of enterohemorrhagic Escherichia coli O157:H7 EDL933 (EHEC) under eleven different environmental conditions including radish sprouts and cattle feces. BMC Genomics 15:353, DOI: 10.1186/1471-2164-15-353

von Neubeck M, Baur C, Krewinkel M, Stoeckel M, Kranz B, Stressler T, Fischer L, Hinrichs J, Scherer S, Wenning M (2015) Biodiversity of refrigerated raw milk microbiota and their enzymatic spoilage potential. Int J Food Microbiol 211:57-65

Neuhaus K, Landstorfer R, Simon S, Schober S, Wright P, Smith C, Backofen R, Wecko R, Keim D, Scherer S (2017) Differentiation of ncRNAs from small mRNAs in Escherichia coli O157:H7 EDL933 (EHEC) by combined RNAseq and RIBOseq – ryhB encodes the regulatory RNA RyhB and a peptide, RyhP. BMC Genomics 8:216 DOI: 10.1186/s12864-017-3586-9

Understanding complex (bio/geo)systems is a pivotal challenge in modern sciences that fuels a constant development of modern analytical technology, finding innovative solutions to resolve and  analyze complex organic mixtures. We aim to establish concepts of complexity and complex small molecules chemistry, in systems subjected to biotic and abiotic transformations, and to develop analytical possibilities to disentangle chemical complexity into its elementary parts (i.e. compositional and structural resolution) as a global integrated approach termed systems chemical analytics. Prof. Schmitt-Kopplin´s major interests are chemical interactions at interfaces in life and earth sciences. His goal is a better understanding of chemical processes i.e. in foods and microbial ecosystems in nutrition, health and environment to identify small molecular keyplayers, their structure and modulating functions. Targeted analysis/quantification of known compounds or non-targeted metabolite profiling are followed using (ultra)high resolution analytical platforms. These involve (µ)separation (hyphenated to MS), spectroscopy (800MHz NMR), mass spectrometry (12 Tesla FTICR-MS), and mathematical methods, to describe and visualize organic structural diversity with space and time resolution in the fields of metabolomics and metallomics.

Within the ZIEL consortium we contribute to metabolomics analysis in targeted and non-targeted way of food and microbiomes in related nutritional studies.

Ph. Schmitt-Kopplin, D. Hemmler, F. Moritz, R. D. Gougeon, M. Lucio, M. Meringer, C. Müller, M. Harir, N. Hertkorn, Systems Chemical Analytics: Introduction to the challenges of chemical complexity analysis, Faraday discussions, 2019, DOI: 10.1039/c9fd00078j

Rychlik M., Ph. Schmitt-Kopplin, Reading From the Crystal Ball: The Laws of Moore and Kurzweil Applied to Mass Spectrometry in Food Analysis, Frontiers in Nutrition, 2020, 7, 9.

K. E. Haslauer, D. Hemmler, Ph. Schmitt-Kopplin, S. S. Heinzmann, Guidelines for the Use of Deuterium Oxide (D2O) in 1H NMR Metabolomics, Analytical Chemistry, 2019, 91, 11063-11069, DOI: 10.1021/acs.analchem.9b01580

Sillner, N., Walker, A., Hemmler, D., Bazanella, M., Heinzmann, S.S., Haller, D., Schmitt-Kopplin, Ph., Milk-Derived Amadori Products in Feces of Formula-Fed Infants, Journal of agricultural and food chemistry, 2019, 67(28), 8061-8069, DOI: 10.1021/acs.jafc.9b01889

Maier, TV, M. Lucio, L.H. Lee, N. VerBerkmoes, C.J. Brislawn, J. Bernhardt, R. Lamendella, J.E. McDermott, N. Bergeron, S.S. Heinzmann, J.T. Morton, A. González Peña, G. Ackermann, R. Knight, K. Riedel, R.M. Krauss, Ph. Schmitt-Kopplin, J.K. Jansson, Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome, MBio, 5(8),  e01343-17, DOI: 10.1128/mBio.01343-17

Recent decades have seen tremendous advances in biomedical knowledge. The challenge now is to bridge the gap between laboratory and clinic, so our increased understanding can be translated into practical benefits for human patients. While genetically modified mice play a prominent role in basic research, their small size and short lifespan make them less suitable for many preclinical studies. Larger species can provide important complementary resources to aid development of safe and effective new medicines and procedures and to study the microbiome in health and disease. We are developing genetically engineered pigs for translational research in several areas, including xenotransplantation and modelling cancers of the gastrointestinal tract and associated organs. We have a herd of pigs that carry a gene-targeted mutation in the APC tumour suppressor gene orthologous to a human mutation responsible for an inherited predisposition to colorectal cancer. Data indicates that the pig phenotype closely mirrors the human disease. We have also assembled a set of modifications necessary to produce a series of further cancer models in pigs. These include conditionally (Cre) activated gene-targeted mutant TP53 and KRAS, and a dual fluorescent reporter cassette placed at the ROSA26 locus to monitor the location of Cre expression and develop methods for in vivo Cre application or gene editing. While our animals are predisposed to GI cancers, disease development and progression is affected by the immune system, diet and microbiome. The ZIEL provides expertise to investigate these interconnected factors and to perform cross-species comparison between animal models and human disease

Publications
Flisikowska, T., Merkl, C., Landmann, T, Eser, S., Rezaei, N., Cui, X., Kurome, M., Zakhartchenko, V., Kessler, B., Wieland, H., Rottmann, O., Schmid, R.M., Schneider, G., Kind, A., Wolf, E., Saur, D. and Schnieke, A. (2012). A porcine model of familial adenomatous polyposis. Gastroenterology 143, 1173-1175.

Saalfrank, A., Janssen, K-P., Ravon, M., Flisikowski, K., Eser, S., Steiger, K., Flisikowska, T., Müller-Fliedner, P., Schulze, E., Brönner, C., Gnann, A., Kappe, E., Böhm, B., Schade, B., Certa, U., Saur, D., Esposito, I., Kind, A. and Schnieke. A. (2016). A porcine model of osteosarcoma. Oncogenesis 5, e210. doi: 10.1038/oncsis.2016.19.

Fischer, K., Kraner-Scheiber, S., Petersen, B., Rieblinger, B., Buermann, A., Flisikowska, T., Flisikowski, K., Christan, S., Edlinger, M., Baars, W., Kurome, M., Zakhartchenko, V., Kessler, B., Plotzki, E., Szczerbal, I., Switonski, M., Denner, J., Wolf, E., Schwinzer, R., Niemann, H., Kind A. and Schnieke A. (2016). Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing. Nature Scientific Reports 6, 29081 doi: 10.1038/srep29081.

Michael Schloter leitet die Abteilung für „Vergleichende Mikrobiomanalysen“ am Helmholtz Zentrum München. Im Fokus stehen Mikrobiome aus unterschiedlichen Habitaten. Hierzu zählen Mikrobiome, die mit Pflanzen assoziiert sind, genauso wie mikrobielle Gemeinschaften, die mit Nutztieren wie Rindern und Schweinen oder mit Insekten Interaktionen bilden. Ein besonderes Augenmerk gilt der Analyse humaner Mikrobiome und deren Rolle für die Gesundheit des Menschen. Durch die Untersuchung dieser sehr unterschiedlichen Habitate erhofft sich Michael Schloter und seine Gruppe generelle Mechanismen und Gesetzmäßigkeiten zu identifizieren, wie Interaktionen zwischen Mikroorganismen ablaufen und wie sich Netzwerkstrukturen bzw. Kommunikationswegen ausbilden. Um diese Ziele zu erreichen nutzt die Abteilung eine Kombination aus Ansätzen die auf der Nutzung stabiler Isotope basieren in Kombination mit modernen Hochdurchsatz-Sequenzierverfahren zur Analyse von mikrobiellen Metagenomen und –transkriptomen.  

Durch die Anbindung an das ZIEL erhofft sich Michael Schloter die Rolle der Ernährung auf die Struktur und Funktion humaner Mikrobiome besser zu verstehen und mit dem Auftreten von chronischen und akuten Stoffwechselerkrankungen zu verknüpfen. Hierzu werden gemeinsam mit Partnern aus dem ZIEL gezielt Experimente in unterschiedlich komplexen Systemen durchgeführt, um mikrobielle Metabolite in Abhängigkeit der Ernährung zu identifizieren, die den Phänotyp der Wirtszellen beeinflussen. Ferner sollen gemeinsam mit den Mitgliedern des ZIEL Ansätze entwickelt werden metagenomische Informationen gezielt zu nutzen, um wichtige Mikroorganismen des humanen Mikrobioms zu isolieren, diese genotypisch zu charakterisieren und in bestehende künstliche Gemeinschaften zu integrieren, deren Wirkung dann im Tiermodell untersucht wird.   

General Research Expertise:
My overarching research theme relies upon the investigation of molecular mechanisms which operate during environmental impact on human health and disease. This includes the research on pollen and its microbiome as well as allergenic substances in general. The study of chronic inflammatory skin diseases goes along with the interest in environmentally triggered and caused non-communicable diseases including allergies. One emphasis is on inflammatory mechanisms, immunological proceedings, and on the study of the skin and gut microbiome. The interrelation of environmental factors such as nutrition with the body system is of major interest to me. Further topics are climate change and its effect on the above mentioned research fields, e. g. on pollen allergenicity and on microbiome abundance/hetereogeneity. As a medical specialist (board certificate: dermatology, venereology, allergology, environmental medicine), I have conducted translational research during the last two decades. The work with patients and the improvement of systemic therapy plus the development of resolute prevention methods are my motivating factors.

ZIEL-oriented Research Profile:

My aims comprises the analysis of the skin microbiome by means of:

1.    descriptive research on chronically inflammable skin diseases

2.    functional analyses of the epithelial-microbe interaction

3.    thorough investigation of nutrition effects on the skin-microbiome composition

To achieve the above three aims, a doctoral candidate will work at the core facility of Dr. Thomas Clavel at the WZW. There, a sequencing device allows for a meticulous study of microbiota. The interdisciplinary ZIEL‑project between Professor Dirk Haller and me is supported by Professor Avidan Neumann and Dr. Matthias Reiger.

Publications:
1.    Kong HH, Andersson B, Clavel T, Common JE, Jackson SA, Olson ND, Segre JA, Traidl-Hoffmann C. “Performing Skin Microbiome Research: A Method to the Madness.” J Invest Dermatol. 2017 Jan 4. pii: S0022-202X(16)32621-5. doi: 10.1016/j.jid.2016.10.033.

2.    Obersteiner A, Gilles S, Frank U, Beck I, Häring F, Ernst D, Rothballer M, Hartmann A, Traidl-Hoffmann C, Schmid M. “Pollen-Associated Microbiome Correlates with Pollution Parameters and the Allergenicity of Pollen.” PLoS One. 2016 Feb 24;11(2):e0149545. doi: 10.1371/journal.pone.0149545.

3.    Lehmann S, Hiller J, van Bergenhenegouwen J, Knippels LM, Garssen J, Traidl-Hoffmann C. “In Vitro Evidence for Immune-Modulatory Properties of Non-Digestible Oligosaccharides: Direct Effect on Human Monocyte Derived Dendritic Cells.” PLoS One. 2015 Jul 6;10(7):e0132304. doi: 10.1371/journal.pone.0132304.

At the Chair for Metabolic Programming, we are studying hormone action in metabolism and immunity. The lab focusses on stress hormones such as cortisol, which bind to nuclear hormone receptors to control gene expression. We are combining cutting edge genomic technologies such as NGS together with bioinformatics, preclinical physiological models and molecular genetics to uncover gene networks controlling metabolism and innate immune responses. Our aim is to decode the DNA sequences governing mammalian physiology. Special areas of interest are transcriptional mechanisms in inflammatory reactions, circadian rhythms, and glucose and lipid metabolism.
Within the ZIEL, we aim to expand our expertise and to collaborate during the investigation of nutritional signals modulating hormone responses and innate immunity. We are excited about future translational studies and interactions within this metabolic network.

Publikationen

PMID: 31706703 DOI: 10.1016/j.molcel.2019.10.007
PMID: 30659202 PMCID: PMC6338785 
DOI: 10.1038/s41467-018-08196-5
PMID: 30096135 PMCID: PMC6105032 
DOI: 10.1371/journal.pbio.2005886