Journ al of Biotechnology in B e r l i n - B r a n d e n b u r g Issue 36 · January 2009 Molecular Nutrition Research and Food Technology Molec ular Nutrition Research as a Basis for Disease Prevention and Health +++ The German Institute of Human Nutrition Potsdam-Rehbrücke – Our Research Focus +++ Health and Nutrition at the TU Berlin – the Center for Preventive Foods +++ The “Brandenburger Ernährungs- und Krebsstudie”: A Potsdam Contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC) +++ Nutrigenomics in Berlin-Brandenburg +++ BEN – the Food Network for the Capital Region + ++ Nutrigenomics and Gene Regulation +++ Food Technology for New Markets from TU Berlin +++ ORGANOBALANCE – From Spin-Off to Successful Probiotics Producer B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y Content Molecular Nutrition Research as a Basis for Disease Prevention and Health The German Institute of Human Nutrition Potsdam-Rehbrücke – Our Research Focus Health and Nutrition at the TU Berlin – the Center for Preventive Foods The “Brandenburger Ernährungs- und Krebsstudie”: A Potsdam Contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC) Nutrigenomics in Berlin-Brandenburg 10 BEN – the Food Network for the Capital Region 13 Nutrigenomics and Gene Regulation 14 Food Technology for New Markets from TU Berlin 16 ORGANOBALANCE – From Spin-Off to Successful Probiotics Producer 18 Impressum Publisher: BioTOP Berlin-Brandenburg Fasanenstraße 85 · D-10623 Berlin Phone +49 30 318622-11 Fax biotop@biotop.de · www.biotop.de Editor: Thilo Spahl +49 30 318622-22 Design & Production: supiran.de Translation: Textbüro Reul GmbH · Frankfurt Photos:  page 3: dreamstime.com/Christophe Testi · page 11: dreamstime.com/Milosluz · page 14/15: dreamstime.com/ Shaik Dawood/Titania1980/Jack Kunnen/Liga Lauzuma/ Janpietruszka/Dorlies Fabri/Missjelena/Evestock/Olga Langerova/Sergei Didyk/Elnur · page 19: BASF SE · others: authors or BioTOP BioTOP is a joint initiative of the state of Berlin and the state of Brandenburg under the umbrella of the TSB Innovationsagentur Berlin GmbH BioTOP is funded by the federal state of Berlin, the federal state of Brandenburg and the Investitionsbank Berlin, cofunded by the European Union (European Fund for Regional Development) BioTOP coordinates the implementation of the master plan of the health region BerlinBrandenburg in the field “Biomedicine/Biotechnology” B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y Molecular Nutrition Research as a Basis for Disease Prevention and Health A third of all health spending is accounted for by illnesses whose origin and progression are influenced directly or indirectly by dietary factors The molecular basis of diet-related illnesses is therefore a challenging area of research for which the bioregion BerlinBrandenburg has strong credentials The close links that exist here between genome research, molecular and clinical nutrition research and plant biotechnology have supported the development of new strategies in recent years to diagnose, prevent and treat dietrelated illnesses Dr Kai Bindseil Director BioTOP Berlin-Brandenburg Particularly in the field of nutrigenomics, which focuses on the interaction between diet or food components and the human genome, the region has produced many new ideas BioProfil Nutrigenomik, funded by the German Ministry of Education and Research (BMBF), is a network in which basic research and its application take place side by side and where research institutes and biotech companies have joined forces to develop new products, particularly for diagnostics The area’s outstanding research facilities, like the German Institute of Human Nutrition, the Innovation Center Health and Nutrition (IGE) of the Technische Universität Berlin, the Max Planck Institute for Molecular Plant Physiology and Charité – Universitätsmedizin Berlin, form the basis for this fruitful cooperation Alongside advancements in biotechnology, many preventive measures are available today that can help considerably to reduce the incidence of many chronic illnesses For the field of preventive health to benefit as quickly as possible from new scientific findings, the master plan of the health cluster Berlin-Brandenburg has made “Prevention, Health Promotion, Rehabilitation and Diet” an independent field of activi­ y­­ t that cooperates closely with the field “Biotech­ nology and Biomedicine” Here the goal is to make Berlin-Brandenburg into a science-led model region for nutrition, health and food In this issue of BioTOPics some of the most im­ ortant nutrition researchers in Berlin-Branp denburg report on research projects and product developments B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y The German Institute of Human Nutrition Potsdam-Rehbrücke – Our Research Focus The German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) investigates the origins of nutrition-associated diseases with the aim of developing new preventive strategies, treatments and dietary recommendations The scientists engaged in interdisciplinary research at the institute use a broad spectrum of scientific, medical and epidemiological research methods The institute’s research is currently focussed on the most important diseases that are associated with dietary factors: obesity, diabetes and cancer Prof Dr Hans-Georg Joost Figure Scientific Director · German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) Tromso Research Focus Metabolic Syndrome and Type-2 Diabetes Metabolic syndrome is the term used to describe a complex of symptoms that include overweight, high blood pressure, insulin resistance and disorders of the lipid metabolism The syndrome has a genetic basis but is usually only triggered by the positive energy balance (high calorie intake and little exercise) that occurs frequently in countries with a “western lifestyle” Incidence as well as severity of this syndrome and its main secondary complication, type-2 diabetes, have increased dramatically in all western countries This trend can also be observed in the Potsdam EPIC (European Prospective Investigation into Cancer and Nutrition) study conducted at the DIfE (Figure 1) Type-2 diabetes is one of the most common and cost intensive chronic diseases today According to the assessment of the CoDiM (Costs of Diabetes Mellitus) study, the direct costs of diabetes in Germany were 30.6 billion euros or 14.2 percent of total spending in the health care system in 2001 Given that the prevalence of diabetes is expected to rise by almost 50 percent between 2000 and 2030, a huge increase in costs must be expected In addition, despite treatment, the secondary complications of metabolic syndrome shorten life expectancy by approximately eight years We can therefore expect a fall in average life expectancy and an explosion in expenses unless we manage to reverse or at least to slow down this trend To so, we need fundamental insights into the causes of metabolic syndrome and effective strategies for the prevention and treatment of obesity and diabetes Using data from the Potsdam EPIC study, the DIfE has therefore developed a diabetes risk test which is already being used by health insurance funds At the same time, DIfE scientists have made important advances in determining the genetic origins of the metabolic syndrome In a mouse model (Figure 2), they identified a natural mutation in the Tbc1d1 gene which affects the regulation of the energy metabolism in the muscles Due Umea Aarhus Cambridge Utrecht Oxford Paris Malmo Copenhagen Potsdam Heidelberg Lyon Milan Turin San Sebastian Florence Barcelona Naples Pamplona Oviedo Granada Murcia Athens Ragusa Centres of the European Prospective Investigation into Cancer and Nutrition (EPIC) to this mutation, the mice lack a particular metabolic enzyme that enables them to remain slim even when fed a high-fat diet, and also protects them against diabetes In the course of their research, the scientists gained profound insight into the function of the gene This provides the basis for developing new therapy and prevention strategies In addition, DIfE scientists are using epidemiological and clinical studies to investigate the interactions between diet, genes and diabetes In the context of the Potsdam EPIC Study, they recently succeeded in showing that a variation of the TCF7L2 gene can determine whether a person can reduce the risk of developing diabetes by eating wholegrain products B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y Figure Figure Fluorescence marked intestinal bacteria Intestinal bacteria can transform nutritional components into toxic substances, which may play a role in carcinogenesis The New Zealand obese mouse gains weight rapidly under a high-fat diet and develops obesity, whereby the proportion of body fat can increase to over 40 percent (left) Despite a very high fat diet, the mice of the Swiss Jim Lambert strain did not gain weight but stayed lean, due to their genetic makeup (right) They also found a link between a high-fat diet, genetic variations of a liver protein that binds fatty acids (FABP) and the human sugar metabolism Research at the institute also focuses on the biological mechanisms that may be responsible for dietary preferences In large sectors of society, people know what constitutes a healthy diet Yet, paradoxically, this knowledge has had little effect on their eating habits Many people still prefer to eat high-calorie food that is less satiable and promotes the development of obesity and type-2 diabetes To determine the role that gustation plays in this phenomenon, scientists at the DIfE are investigating the molecular mechanisms responsible for taste perception They have already succeeded in finding different receptor variants associated with different taste perceptions Links between Diet and Cancer Many epidemiological data confirm the assumption that diet plays a major role in the development of cancer The DIfE has contributed to this insight with its participation in the multi-centre Europe-wide EPIC study The findings of this study show that a low consumption of fibers and a high consumption of red meat is associated with a higher incidence of colorectal cancer DIfE also investigated the effect of fruit and vegetable consumption on different types of cancer and found indications of a reduced risk for cancer of the lung and of the oropharyngeal epithelium The study also indicated that overweight is an important risk factor for colon cancer (men and women) and for cancer of the kidney and breast (women) However, epidemiological studies not unequivocally prove causal connections between diet and cancer This is why the DIfE is also using biochemical, molecular and microbiological methods as well as cellular testing systems and animal models to establish causality of the associations between cancer and diet Preliminary findings support the assumption that the metabolic conversion of foreign substances absorbed with food may play a role in the development of cancer Metabolism of xenobiotics can inactivate carcinogenic substances, but can also activate them Here, the genetically determined variants of the enzymes involved in the so-called “detoxification metabolism” play a decisive role Researchers at the institute were able to show that the bacteria in normal intestinal flora (Figure 3) can convert foreign substances into toxic, mutagenic or possibly carcinogenic substances One example is the transformation of arbutin into the mutagenic substance hydrochinone, which triggered cancer in animal experiments High concentrations of arbutin are found in pear skins and in wheat Researchers at the DIfE are also studying the influence of micronutrients like selenium on the development of colon cancer and have already succeeded in identifying a selenium protein (an enzyme) produced by the body itself which is synthesized more intensively in human colon tumors and can be induced by components of cruciferous plants However, more research is required to show the significance of these processes for the development or prevention of cancer The scientists at the institute have therefore developed “humanized” animal models which they will use to study the relationship between nutrition, inflammatory processes and the development of colon cancer in vivo B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y Health and Nutrition at the TU Berlin – the Center for Preventive Foods The Center for Preventive Foods (CPF), founded in 2007 by the Technical University of Berlin, brings together important actors from nutrition-relevant sectors of the research environment in Berlin-Brandenburg It combines R&D activities in the field of preventive foods and will intensify interdisciplinary cooperation between biotechnology, food chemistry and technology, nutrition science, biology and medicine Dr Edeltraud Mast-Gerlach Center for Preventive Foods mast-gerlach@lb.tu-berlin.de The concentration of scientists in agricultural, food and nutritional research in Berlin-Brandenburg is among the highest in Europe The leading institutions in this field are the three universities of Berlin, the University of Potsdam, the institutes of the Max Planck, Fraunhofer and Leibniz societies and the universities of applied sciences in Berlin and Brandenburg The food industry, which plays an important role in the economy of the Berlin-Brandenburg region, is also an important actor in this field Figure The Aims of the Center One aim of the Center for Preventive Foods is to bring together existing resources along the entire added value chain and develop networks between them This is both desirable and necessary, because demand for interdisciplinary cooperation in both national and international projects is growing steadily Linking up the competences of relevant regional research institutions and industrial companies will produce synergy effects, which in turn allow us to press ahead with the development of functional foods with a preventive effect The research network of the Center for Preventive Foods – Research institutes, companies and associations participating in the CPF UP MPI Golm Fraunhofer IAP ATB BEN IGV DIfE VLB TFH HU OB TU FU BioTOP WVEB BAM BfR IGZ Research uuBfR – Federal Institute for Risk Assessment uuATB – Leibniz Institute of Agricultural Engineering in Bornim uuDIfE - German Institute of Human Nutrition in Nuthetal uuIGZ – Institute of Vegetable and Ornamental Crops in Großbeeren uuFraunhofer IAP – Fraunhofer Institute for Applied Polymer Research in Golm uuBAM – Federal Institute for Materials Research and Testing in Berlin Industry uuIGV- Institut für Getreideverarbeitung GmbH in Nuthetal uuOB – Organobalance GmbH in Berlin NGOs uuBioTOP uuWVEB – Association of the Food Industry in Berlin and Brandenburg uuBEN – Brandenburg Food Network FH Lausitz A further goal of the CPF is to provide new dynamism for industry by innovations in the food and nutrition sciences and enhance knowledge transfer in the functional food sector by purposefully networking science and industry The CPF mission is to conduct research into food components, starting with agricultural production and looking at the whole value-added chain all the way to the consumer In doing so, we hope to provide scientific evidence of their health-promoting effects and to produce targeted preventive foodstuffs Our research aims to identify food components with preventive effects and analyze compounds along the value added B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y Figure 2: The interdisciplinary research concept of the CPF – Research along the value added chain Production systems Root cell cultures · Cell and tissue cultures · Plants and algae · Microorganisms Production Detection methods Target substances Food processing and analytics Food component extraction · Post-harvest technology · Processing Bioactivity studies and molecular mechanisms Bioavailability · Health benefits/prevention · Toxicology Functional foods Communication chain, from biosynthesis to processing, and ultimately to consumption “Our great strength is that we can study the entire food chain from production to the consumer”, says the spokesman of the Center, Prof Dr Dietrich Knorr “Our focus is on functional food components of plant or microbial origin with a health-promoting effect We are interested, for example, in sweet proteins as non-calorific sweeteners as well as flavonoids and other secondary plant metabolites, trace elements and polyunsaturated fatty acids What is always important for foods with functional components are sound scientific data and that the nutrition character of the products is preserved” The use of foods that show additional health benefits must always be accompanied by a public information campaign about a balanced diet to ensure that foods with additional health benefits supplement the regular diet in a sensible way New Requirements for Food Dietary awareness and the eating habits of the population have changed considerably in recent years In the past it was important to eat enough protein, essential fatty acids and vitamins, whereas now the emphasis is on healthy nutrition Secondary food components like flavonoids or polyphenols are increasingly becoming valuable elements of our diet These bioactive compounds can have a preventive effect and lower the risk of developing certain diseases like cancer or cardio-vascular disease The molecular mechanisms underlying this effect are still unknown, however Often it is not the original substance but metabolites produced either by the organism itself or by intestinal bacteria that have positive properties In our research, we aim to identify these metabolites as well as the original substances and test them to discover their properties The CPF has various model systems, ranging from animal models, cell cultures and reporter gene constructs to the spectroscopic methods used to demonstrate cancerpreventing effects on the skin The studies are intended to show, for example, whether endogenous protective mechanisms can be induced or strengthened The idea would then be to find complementary combinations of food components and possibly preserve and refine them by cultivation and processing We intend to focus on redox systems as well as probiotics and prebiotics and develop an integrated matrix of coordinated projects for gentle and consumer-friendly processing The CPF will implement all steps, from optimizing the formation of the substances in plants, microorganisms and/or plant cell cultures to raising the level of the food components in foodstuffs during processing, identifying the presence of food components in the organism and demonstrating their bioavailability and biological effects We intend to focus on plant products and look at the entire chain from cultivation to harvest, and from processing to food intake and biological effect Ultimately the medical, nutritional and biotechnological knowledge so obtained will provide the know-how for the industrial production of preventive foodstuffs and for the manufacture of health-promoting products Together with the Center for Innovative Health Technologies ZiG, the Center for Preventive Foods will work in the pioneering field of TU Berlin: “Health and Nutrition” The committees of the TU Berlin recently approved the launch of the Innovation Centre Health and Nutrition In these pioneering fields of technology and innovation, we will search for long-term solutions to important social needs and global problems Figure Innovation Center Health and Nutrition Health Technologies Communication Monitoring Health sector Nutrition and Preventive Foods ZiG ZiG and CPF CPF Teaching and Training Knowledge and Technology Transfer B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y The “Brandenburger Ernährungs- und Krebsstudie”: A Potsdam Contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC) The long tradition of nutrition research in Brandenburg began when the Russian military administration decided on 10 June 1946 to move the Institute for Nutrition and Food Science from Dahlem to Potsdam-Rehbrücke It was joined in 1948 by the Institute for Vitamin Testing and Vitamin Research from Leipzig Prof Dr Heiner Boeing German Institute of Human Nutrition Potsdam-Rehbrücke Department of Epidemiology boeing@dife.de These initial foundations later evolved to become an Institute of the Academy of Sciences, and the research into nutrition conducted in Rehbrücke during this period not only had an impact on research in this field in the countries of the Warsaw Pact but also on nutrition research in West Germany As a student at the University of Giessen in West Germany, I often heard lecturers referring to the research being conducted at this Institute and express the wish for the different nutrition research centres in Germany to cooperate more closely intensively in various European working groups during the 1990s Under the coordination of the International Cancer Research Agency in Lyon, they formed a consortium, which initially included the German Cancer Research Centre in Heidelberg as the German partner The founding of the German Institute of Human Nutrition and the establishment of the working group “Medical Epidemiology” there offered an opportunity to apply the approaches being discussed at the European level in Brandenburg too At that time, the consortium took a certain amount of convincing to persuade it that Potsdam was a suitWhen the German Institute of Human Nutrition able study centre, because all the other 22 cenwas founded as a Leibniz Institute in Potsdam- tres of the EPIC consortium came from regions Rehbrücke following German reunification, that had been part of the West during the Cold nutrition research was put on a new scientific War (Figure 1, Page 4) and financial basis The founding members considered it particularly important to orient the The Brandenburg component of the European Institute more strongly towards research into long-term EPIC study was launched in 1994 human nutrition and to translate basic research with funding from the German Federal Minisfindings into dietary habits of the population try of Research and Technology Some 120,000 on sound scientific grounds Epidemiology was inhabitants of Brandenburg received letters askassigned such a function alongside with clini- ing them to take part in the study and more cal research Epidemiology therefore initially than 27,500 of them agreed All participants became a working group and in 1996 a depart- were asked to fill out questionnaires at home ment at the DIfE and then invited to come to a study centre at the Health Authority of the City of Potsdam, Epidemiology is a relatively new research disci- where further interviews were conducted, the pline in Germany One of its tasks is to discover participants’ blood pressure was measured, ways of lowering the risk of disease by obser- and anthropometric measurements were taken vation and targeted intervention The obser- together with a blood sample This collection vational approach requires large groups of the of data and biological materials forms the basis population as participants and active coopera- for assessing the risks of developing a range of tion from many people to draw long-term con- chronic diseases clusions about how to prevent chronic diseases For the DIfE, dietary and diet-related factors like obesity are of prime concern The launch of a major observational study was discussed B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y To evaluate the relationships between the risk of disease and diet and other life-style factors, it is necessary to record medical events in the cohorts for the disease end points comprehensively and accurately over a number of years that are of interest to researchers To so, all participants in the study are contacted by questionnaire every two to three years and asked to report on their new diseases In this mailed questionnaires, participants with a new disease are asked to provide information about the treating physician, whom we then contact to obtain a medical diagnosis according to the international classification of diseases according to the World Health Organization A key factor in the scientific quality of a long-term study is the percentage of returned questionnaires Due to the strong commitment of all study participants, our response rate is high compared to other studies world-wide, with a return rate for each of the questionnaires (with one exception) of more than 95 % Obesity has an important role to play in this research, for it is both conditioned by diet and also has major consequences for the body’s metabolism Following this sequence of relationships from diet to adipositas and further to risk of disease is a further research focus of the Department of Epidemiology With its large cohort size, the EPIC consortium is one of the most active research groups with more than 500 publications up to now We estimate that around 200 scientists currently work with the EPIC data, including the roughly ten researchers at the Department of Epidemiology at the DIfE The EPIC research themes are not always of direct interest to the study participants; rather, EPIC research sometimes addresses very specific research questions However, also their findings will be used in the long-term to prevent disease From the findings of this and other available studies we are beginning to identify a set of dietary and lifestyle factors that can lead to a considerable reduction of disease risk This includes a diet with a strong component of wholemeal cereal products and high consumption of fruit and vegetables, in combination with stable body weight – around 25 BMI – over the course of a lifetime and a minimum level of physical exercise Another important factor, of course, is not to smoke In our study we were able to show that subjects with a lifestyle of this kind had only a quarter the risk of developing diseases as those with all risk factors (Figure 2) The extensive collection of data on dietary and lifestyle factors gathered at the beginning of the study will be supplemented by further information enquired during the course of the study Together with the information on participants’ diseases, it forms the basis for the assessment of risk for the various chronic diseases These risk analyses are conducted both for the EPIC Potsdam population and jointly with other European study centres Overall, the EPIC consortium has been very successful in recruiting study participants and now has data on more than 520,000 study participants The study is therefore one of the largest worldwide and a leader in the assessment of risk relationships in Europe The focus on diet in this study is of considerable scientific importance for the Department of Epidemiology, since diet is one of the institute’s main research themes Potsdam’s contribution to the EPIC consortium therefore includes methodology for recording dietary data, evaluating dietary patterns and investigating the role of dietary factors for predicting various diseases A further focus is on anthropometric parameters and indices, including the distribution of body fat The endpoints of interests are type-2 diabetes, cardio-vascular diseases and cancer In this way, the study participants from Brandenburg have helped establish further milestones in determining how we should shape our lifestyles to avoid the occurrence of chronic diseases in youth and middle-age and reduce the risk of mortality Figure 1,2 Relative Risk 1,0 0,8 0,6 0,4 0,2 0 Preventive Factors Reducing the combined risk of type-2 diabetes, heart attack, stroke and cancer in the EPIC-Potsdam Study in connection with the presence of preventive factors (no smoking, no adipositas, a healthy diet and sufficient exercise) B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y 10 Nutrigenomics in Berlin-Brandenburg The metabolism is the basis for all life because it provides the energy for the biological processes in the body This involves a complex network of biological reactions which facilitate the conversion of the energy gained from food into metabolic energy and at the same provide the components for constructing and maintaining the organism Metabolic pathways are like a transport network within a cell, which must manage many diverse functions ranging from the intake and utilisation of food to getting rid of waste Prof Dr Andreas F.H Pfeiffer The many steps involved, from food ingestion and chewing, to its breakdown into smaller units during digestion in the intestines, its absorption by the body and transportation to the cells, require many special functions of individual organs, which then provide the energy to different functions of the organism – as in the heart, brain, muscles or sensory organs German Institute of Human Nutrition Potsdam-Rehbrücke and Charité – Universitätsmedizin Berlin All these processes are carried out by proteins, whose structure and function are defined in the genome and which every human being possesses in a large number of variations, which differ only minimally from those of others These tiny differences are what makes every individual different and determine his or her individual foodprocessing profile Nutrigenomics is devoted to trying to understand these differences and includes two main fields of research: One field concerns differences in the genetic blueprints, which ultimately produce different metabolic functions and hence variations in the risk of developing certain diseases The other field describes the direct reaction of the metabolism to the intake of food, through changes in gene expression in various organs To give an example: eating potatoes – i.e., carbohydrates – causes the organism to react immediately, programming the organ systems involved to be ready for future intake of food and thus ensuring that they remain in a fit state for that activity a sufficient number of people willing to be examined more closely and who will consent to researchers studying their genetic profile A collective of this kind, which now comprises 2,600 participants, was established in our Department of Clinical Nutrition at the German Institute for Human Nutrition under the auspices of a BMBF project entitled MESY-BEPO – Metabolisches Syndrom Berlin Potsdam In a first step, we characterised the metabolism of the study subjects, looking at their blood fat values and at the various blood enzymes in the liver, intestines, fat tissue, muscles and other organs We then asked the participants to undergo a glucose tolerance test Here the test subjects drink 75 grams of sugar, and researchers then study the reaction of the metabolism over a period of three hours, measuring both the rise in the blood sugar level and the hormonal responses to the sugar This test provides a lot of information about the metabolism We also characterised the test subjects with regard to the presence of many genes in their metabolism A first example concerns how eating a healthy diet affects the metabolism It is necessary first of all to find out how quickly the metabolism reacts to food intake For these tests we used pairs of twins and asked one of them to eat a healthy diet and the other an unhealthy diet for a period of four weeks During this time we characterised their metabolism It was found that, even after just four weeks, the sugar metabolism of the twin eating a healthy diet had improved The study of these nutrigenomic processes has significantly – the rise in the blood sugar level produced the first advances in recent years after drinking 75 grams of sugar was lower and Which strategy can be used to find out to deter- required considerably less insulin to absorb the mine the genetic differences which are impor- sugar into the metabolism In other words, the tant to the metabolism? First of all, we need twins eating a healthy diet had high insulin B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y efficacy The other twins, who had eaten a diet richer in fat and lower in fibre – a diet rather typical for Germany – showed a deterioration of the metabolism, with a greater rise in the sugar level in the glucose tolerance test and a considerable rise in the level of insulin, indicating lower insulin efficacy or insulin resistance It is known from population studies that insulin resistance is associated with disorders of the fat metabolism, high blood pressure and an increased tendency towards diabetes and, in the long term, a higher risk of heart attack and stroke Determining the function of variants of individual genes is considerably more complicated One way of doing so is to use the hypothesis-driven approach in which a hypothesis about the function of a particular protein is used as a starting point We employed this approach to study a fatty acid binding protein from the liver We knew from earlier studies that the sugar production of the liver is increased by free fatty acids These, in turn, increase after food intake, causing the liver to produce more sugar We therefore asked two groups of 10 test subjects from our study collective, which had either a particular genetic variant of this fatty acid binding protein or the opposite variant, to participate in the study Here fat was infused into the subjects to produce a level of fatty acids resembling that following a heavy meal At the same time the various hormones like insulin, growth hormones or glucagon, which regulate the liver metabolism, were turned off by administering the inhibitor hormone somatostatin, and physiological levels of these hormones were produced through infusions The purpose of this procedure was to control the regulation of the metabolism by food-dependent hormones Under these conditions, we were able to investigate how gene polymorphism controls the sugar production of the liver In fact, the experiment showed that one gene variant led to marked sugar production in response to the fats, whereas the other showed much less marked sugar production Among the subjects making up the MESY-BEPO collective, this gene variant was consistently associated with a significantly higher body weight of about one body mass index unit, in other words, an additional kilogram of body weight per square metre of body surface To identify a larger number of gene variants that are significant for nutrigenomics without using hypotheses, we need more precise information about individual differences in the food response and the scale of the differences We are currently conducting experiments to determine these differences With the information obtained, we plan to conduct a genome-wide study to map the relationship between certain reactions to food intake and gene polymorphism in the entire genome Studies of this kind, which examine around one million gene variants per person, have recently succeeded in identifying new gene loci, which may determine a tendency towards overweight, diabetes or simply body size Another strategy for investigating individual responses to food intake uses so-called gene expression analysis Here we exam- ine how certain tissues behave in response to food-related stimuli Important stimuli of this kind are the hormonal responses triggered by food intake We know, for example, that the release of insulin is triggered in this way and that insulin regulates several hundred genes in the liver Every time food is eaten, intestinal hormones – so-called incretins – are released, which both intensify the release of insulin triggered by food intake and also perform other functions that we as yet know little about To study their function in more detail we gave 15 voluntary test subjects an infusion of the incretin “Glucose-induced Insulino-mimetic Peptide” (GIP) and looked at the impact it had on gene expression in fat tissue GIP is normally released by the cells in the intestinal mucosa, so that the level of GIP rises after every meal The more carbohydrates and fat a meal contains, the greater the increase in the level of this hormone We infused this hormone by a drip over a period of four hours and took a small sample of tissue from the stomach fat before and after the infusion From this fat tissue we extracted the information for the protein blueprints, the mRNA, and then tested the change of its expression levels with a so-called gene array Using such a high density of gene samples on a slide is now standard research practice In our case, they contained 44,000 different gene probes, which cover practically all known human genes at least once With these gene arrays, mRNA production can be measured quantitatively We were surprised to find that the GIP stimulated the expression of genes that play a role in inflammatory reactions This fits with our observation that when a person becomes overweight and the amount of abdominal fat increases, an inflammatory reaction occurs in the fat tissue Among overweight people, the number of inflammatory cells in fat tissue is raised, probably to protect the fat tissue from infection in the event of injury The astonishing thing is that it only takes a food stimulus to trigger the release of hormones that attract inflammatory cells to the fat tissue An example of a messenger substance of this kind is MCP1 (monocyte chemoattractant protein 1), a so-called chemokine Other interesting genes that we found were those that regulate fat absorption and storage and those that regulate the biorhythms and energy balance All in all, GIP has proven to be a hormone that manages energy intake and storage very effectively For this reason, it is conducive to weight gain Foods that cause less GIP to be released are therefore probably helpful in maintaining normal body weight 11 B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y 12 This study enabled us to better understand the function of individual metabolic pathways and ultimately to characterise them in individuals Because people’s genetic make-up differs, we would expect some people to remain healthier if they eat a lot of carbohydrates, whereas for others carbohydrates are less important or even harmful and they better with a high-protein or even a high-fat diet This almost certainly applies to the propensity to put on weight as well We expect that it will in the future become far more plausible to offer people customised dietary advice and information and that we will be able to predict which foods they should eat if they wish to live a long and healthy life We also expect to be able to influence the risk of developing quite a number of diseases by the diet Examples include longchain fatty acids, which are connected with inflammatory reactions They include alpha-linoleic acid, an omega fatty acid, or alpha-linolenic acid, an omega fatty acid We already know that people with gene variants in the enzymes that process these fatty acids, e.g delta-6-desaturation and delta-5-desaturation, are prone to hay fever and allergic eczema to different degrees If we can determine more accurately how this connection works, we will be able to influence the incidence of these diseases via diet Influence of Diet on the Risk of Metabolic Illnesses through Hormonal Regulation: After four weeks on a healthy DGE [German Nutrition Society] diet 22.06.2007 22.06.2007 20.07.2007 Insulin mlU/ml Glucose mg/dl 20.07.2007 30 60 90 Time of measurement (minutes) 120 30 60 90 Time of measurement (minutes) 21-year-old woman 162 cm, 64.5 kg (BMI 24.6 kg/m2) = > 63.7 kg (BMI 24.3 kg/m2) · Waist: 76.5 =>74.9 cm Hips: 98.5 =>96.5 (WHR: 0.777 = > 0.776) · 24.3 kg (37.7%) proportion of fat =>24.1 kg (37.7%) · 40.1 kg (62.3%) fat-free mass =>39.7 kg (62.3%) 120 B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y BEN – the Food Network for the Capital Region Anja-Christin Faber Service- und BeratungsCenter (SBC) Industrie- und Handelskammer Potsdam faber@potsdam.ihk.de In the Capital Region , industry and science are integrated closely Following this trend, the food industry has formed a successful network– the Brandenburg Food Industry Network (BEN), which is managed jointly by the Potsdam Chamber of Commerce and Industry and pro agro e V conducted in the scientific institutions and universities of the region Based on their good knowledge of markets and products, they are well placed to assess requirements very well and request the specific technical solutions they need The relevant issues range from questions of product presentation and packaging to many different incremental innovations in production The Food Industry – An Important Sector processes or quality features, or the development of new prodWith more than 10,000 employees and sales worth more than 2.5 ucts, particularly for market niches Themes that currently receive billion Euros a year, the mainly small and medium-sized compa- a lot of attention are hypoallergenic foods and the development nies in the food industry form one of the most important industries and marketing of products for the elderly The network organizes in Brandenburg The food sector includes many agricultural enter- workshops on these issues and provides support, such as checkprises and food processing companies, which produce mainly lists, to help companies tailor products to particular target groups meat and sausage, but also bakery products, confectionery, fruits and vegetables, and dairy products Alongside well-known com- Food Safety and Hygiene panies like Campina Milchprodukte GmbH, Katjes Bonbonfabrik Food safety continues to be a highly sensitive issue Here both the GmbH or Coca Cola GmbH, which have production facilities in the market and the authorities continually demand improvements region around Berlin, a number of regional companies like the At the same time, there is a steady supply of new findings from fruit and vegetable processing company Spreewaldkonserve Golßen microbiological research, which can be translated into quality GmbH, Werder Feinkost GmbH or JÜTRO Konservenfabrik GmbH & assurance technologies in cooperation with the companies using Co KG have succeeded in establishing themselves on the market them The network allows its members to stay up to date with developments in the field of food hygiene and helps them apply The Network new advances in practice Here it has two experienced and comTo support these companies, the Potsdam Chamber of Industry mitted partners in IFTA Akademie GmbH and matec GmbH from and Commerce (IHK) founded the Brandenburger Ernährungs- Wildau A tradition of cooperation between these companies Netzwerk (Brandenburg Food Industry Network) in 2004 Funded and firms in the food industry going back many years ensures an by the Brandenburg Ministry of Labor, Social Affairs, Health and atmosphere of openness and trust in meetings and discussions Family, the network provided assistance for 30 companies within two years As part of the funding program of the Brandenburg Cooperation Beyond the Region and Internationalization Ministry of Economics, the network was reorganized in 2008 IHK BEN has also cooperated with organizations outside the region Potsdam and pro agro – the Association for Promoting Rural Areas for many years The association holds regular meetings with food in the State of Brandenburg – now work hand in hand to network networks from other parts of Germany to exchange experiences and support companies in the food sector The aim is to improve Particularly the older networks in this “Cluster Council” are enorcooperation between companies and institutions that have close mously important to BEN as providers of know how A number of links with industry both in- and outside the region and thereby joint projects are planned for the future International networks increase their competitiveness A particularly important concern is are also important for Brandenburg’s food industry BEN is theretechnology transfer The network now includes 54 member com- fore cultivating contacts with partners in a number of countries, panies and institutions Nine working groups, established and including Belgium and England, to meet other regional food netled by members of BEN e V., have met to discuss issues like prod- works and develop joint projects, mainly devoted to know-how uct development, logistics, regional products, agriculture, healthy transfer The international cooperation event PROMOFOOD, which nutrition, marketing and food safety takes place in Potsdam every year, offers an excellent forum for exchange between national and international cooperation partners Product Innovation Although our food has come from the same sources for thousands The region’s companies have recognized the opportunities that of years, innovations are just as important in the food industry networking with each other and with research facilities and techas in other sectors Small and medium-sized companies, which nology providers offers The projects in hand are challenging often not have R&D departments of their own, need networks requiring successful implementation – as a network we can make and cooperation to benefit from application-oriented research that happen 13 B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y 14 Nutrigenomics and Gene Regulation As a newly founded research group in 2008 at the Max Planck Institute for Molecular Genetics, the Nutrigenomics and Gene Regulation Laboratory has been exploring health implications of the interaction between nutrition and genomics or the so-called “nutri­ genomics” The interaction and the regulation of genes play an important role in various molecular processes of human metabolic diseases Chung-Ting Han Susanne Holzhauser Sascha Sauer Max Planck Institute for Molecular Genetics sauer@molgen.mpg.de Saponins Quercetin Myristicin One emphasis of our research group lies in analysing the modulation of gene expression­ in cellular differentiation This process can be significantly influenced through the interaction between genes and naturally occurring compounds found in edible biomaterials Consequently, as the second emphasis of our research group we study the capability and mechanisms of natural products­ to interact with genes and gene products The multidisciplinary approach of our research group consists of fundamental as well as applied research The data obtained by our systematic studies, described in more detail for the natural product resveratrol below, will be useful for modeling effects of natural products on, for instance, fat cell differentiation Clearly, natural­ products with a beneficially active profile can be further exploited, for the development of nutraceuticals and/or for the development of novel chemical structures for treating insulin resistance and obesity observation that the French have relatively low incidence rates of heart disease, dispite having a diet relatively rich in fats Nevertheless, how can resveratrol benefit our health? Resveratrol in Wine Resveratrol is a phytoalexin produced by several plants when undergoing attack by pathogens such as bacteria or fungi After fermentation of red grapes, resveratrol is easily released from the skin Therefore, red wine is the best natural source of resveratrol To date, there is mounting evidence on the potential benefits of resveratrol in slowing the aging process, extending the lifespan, and preventing the manifestation of type II diabetes Resveratrol and Sirtuin Resveratrol is thought to interact with a human­ deacetylating enzyme called “sirtuin 1”.­­­ The potential resveratrol-sirtuin interaction deserves much attention because sirtuin has been demonstrated to influence the activity of metabolic sensors and their subsequent effect on gene expression In rodents, resveratrol has To Your Health! been shown to mimic dietary energy/calorie When toasting with a glass of wine, we say restriction (that is, food deprivation without “Zum Wohl” in German, “Santé” in French, malnutrition) by activating sirtuin and extend “Alla salute” in Italian, and “Salud” in Span- the healthy lifespan of animals fed a high-fat ish Coincidently, all literal translations refer to diet This is accompanied by lower blood glu“to your health” in English Perhaps since long cose and increased insulin sensitivity in diabetago, people have already realized the associa- ic-prone rodents Other protective functions of tion between wine and health But not until sirtuin have been proposed in the regulation of 1992 a natural compound called resveratrol was molecular key players that are involved in gene identified in red wine Since then scientists have expression and post-translational modifications become interested in exploring the potential of proteins For example in fat cells, sirtuin can health benefits of resveratrol The discovery of inhibit adipogenesis by decreasing white adiporesveratrol also leads to the speculation that it cyte formation through nuclear receptor PPARg might help explain the “French Paradox”, the inhibition by deacetylating the repressor-pro- B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y 15 Naringenin Anthocyanins Zeaxanthin Lutein Resveratrol b-Carotene Sulphoraphane Lycopene A wide variety of phytochemicals can be found in food supply (modified from photo by Keith Weller, USDA/ARS) tein NCoR In the pancreas, sirtuin is shown to improve insulin secretion by repressing the UCP-2 protein in the -cells In the liver, sirtuin promotes gluconeogenesis via FOXO1 and PGC-1a by inhibiting glucose formation and stimulating glucose uptake by cells Moreover, sirtuin is a positive regulator of LXR, which is a cholesterol sensor in the liver and regulates whole-body cholesterol and lipid homeostasis In the mitochondria of brown adipose tissue and skeletal muscle cells, sirtuin can stimulate the turnover of cellular energy metabolism also with the help from PGC-1a Additionally, sirtuin promotes the survival of muscle cells in the heart and protects neurons from cell death via NFkB signaling cascade in the brain tissue Sirtuin can also deacetylate histones of the chromatin to repress gene transcription on a more global level In a nutshell, sirtuin seems like a promising target in the discovery of dietary therapeutics that can either activate or inhibit the enzymatic activity of this protein The interactions of these molecules with sirtuin are currently being characterised using biophysical, cell-based biochemical, physiological and modern genomic methods, such as secondgeneration sequencing Second-generation sequencing with Solexa technology (www.illumina.com) can be applied efficiently for studying RNA expression Secondly, the interaction of DNA-binding proteins such as nuclear receptors can be analysed accurately in different cell states Therefore, a specific antibody against the protein under investigation is used for immunoprecipitation including the DNA sequences of the genome that interact with the precipitated protein The DNA sequences of the genome that bind with the protein of interest are then identified and quantitatively analysed using the Solexa sequencer In order to ascertain the effects of natural products on the proteome quantitatively, high-resolution electrospray ionisation (ESI) mass spectrometry will be employed Our Approach Although resveratrol is a strong activator of sirtuin 1, the bioavailability of resveratrol is fairly low in humans In order to identify alternative sirtuin modulators, we utilize a systematic approach to screen and characterise more potent compounds that are derived from edible biomaterials (Figure 2) In the first screen we identified a number of molecules that showed significantly higher activation for sirtuin than resveratrol Our Projects In different projects funded by the BMBF, our research group studies the mechanisms of a number of nuclear receptors and chromatin-modifying proteins involved in metabolic processes as well as the interaction of these proteins with small molecules, i.e natural products To pursue our research goals, in the frame of the European FP-7 large-integrated project READNA, we are additionally and actively developing modifications of cutting-edge technologies such as second-generation sequencing for covering the spectrum of our research projects Figure in vitro Highthroughput Screening in vivo Biophysical Property Molecular Pathways Genomic and Proteomic Profiling Mathematical Modelling of Cellular Pathways Animal Model With a broad spectrum of research objectives, dynamic approaches are used to discover potential sirtuin modulators for the prevention and treatment of metabolic diseases B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y 16 Food Technology for New Markets from TU Berlin Every 18 to 21 days, we need to consume a volume of food and fluids equivalent to our body weight Within an average life-span, we therefore need around 100 tons of food Because of the growing world population and the associated reduction in agricultural areas, it is essential to find ever more efficient ways of producing and processing food, which use resources sparingly Prof Dr.-Ing Dietrich Knorr Berlin University of Technology Institute of Food Biotechnology and Food Chemistry Department of Food Biotechnology and Food Process Engineering dietrich.knorr@tu-berlin.de Food Processing The main priorities in food processing are that the products are safe, the methods of processing them are sustainable and that the products themselves are functional (http://etp.ciaa.be) Current research in food process engineering at Berlin University of Technology focuses on developing sustainable and gentle processing technologies The methods investigated include hydrostatic high pressure, pulsed electric fields, ultra-sound, super-critical carbon dioxide, high-pressure homogenization, light pulses (with Cornell University, Ithaca, NY), infra-red radiation (with SiK, Gothenburg), cold plasma (with the Leibnitz Institute of Agricultural Technology Bornim), sub-critical water (with the German Institute for Food Technology, Quakenbrück) and combinations of these methods Food Safety Based partly on research conducted at TU Berlin, hydrostatic high pressure technology, in which water or oils are used as the pressuretransmitting media, is now being used industrially worldwide to pasteurize and modify foods and food constituents High-pressure sterilization, which uses a combination of high pressure and temperature, is very close to being ready for industrial use Basic research at Berlin University of Technology, which showed that not only bacterial spores, but prions and viruses, too, can be successfully inactivated, has won international research prizes (www.tu-berlin.de/~foodtech) In high-pressure/high-temperature processes, the adiabatic heat generated and the fairly even distribution of temperature within the products are used to guarantee the gentle processing of foods and thereby prevent the destruction of nutrients High-pressure low-temperature processes permit foods to be frozen and thawed without destroying nutrients and open up a wide range of new applications, such as storing organs at low temperatures and inactivating pathogenic micro-organisms in frozen foods by alternation of pressure-induced ice-crystal forms and the associated changes in volume The principle of action of high-pressure processes (activation volume) differs from that of thermal (activation energy) processes and acts specifically on pathogenic micro-organisms like salmonella or listeria Since only non-covalent bonds are affected, valuable food components (like vitamins or aromas) are preserved The Senate Commission on Food Safety (SKLM) of the German Research Foundation (www.dfg.de) has issued a safety evaluation of the process, the first one world-wide Sustainable Processes Pulsed electric field treatment can be used to stress biological membranes and permeabilize them reversibly or irreversibly This makes it possible to accelerate mass transfer operations (e.g., drying, extraction, compression, expression) and to implement selected structural changes, for instance to also improve water absorption About 250 kJ/kg are required for thermal permeabilization of plant membranes (e.g of sugar beet) Permeabiliziation using pulsed electric fields requires only 5-10 kJ/kg and processing times in the order of seconds In cooperation with the German Institute for Food Technology (DIL) and as part of an integrated EU project (www.novelq.org), applied basic research is being conducted into this process to make it industrially viable This process, too, has been subjected to a safety evaluation B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y The Importance of Food Technology One of the most important goals of the European Technology Platform: Food for Life (http://etp.ciaa.be) is to create functional foods tailored to the preferences acceptance and needs of consumers, with the long-term objective of personalizing food To generate tailor made foods, it is essential to understand the relationships between food and food component processing and the structures and functions affected This research challenge is reflected in the development plan of the Food Technology Department at Berlin University of Technology, in which the three disciplines Figure A B Facility for pulsed electric field (A) – and high-pressure treatment (B) on a pilot scale at Berlin University of Technology Parameters for a) continuous 600 kg/h, maximum voltage 50 kV, maximum frequency 400 Hz; b) batch max pressure 800 MPa, max T 60°C, volume 0.7 L by the SKLM of the DFG (www.dfg.de) High-pressure treatment in the lower pressure area of approx 100 MPa can be used to induce stress and thereby raise the thermal resistance of probiotic starter cultures The cultures can then be preserved using the spray-drying method rather the freeze-drying method more common in the food sector This reduces the energy required from around100,000 kJ/kg water removed to 4,000–6,000 kJ/kg Production Functionality Modern targeted and customized processing methods for functional foods should not only aim to ensure product safety and quality They should also provide additional benefits, such as superior nutritional quality Pulsed electric fields in the lowenergy range facilitate stress induction (for example, in apples, grapes and oil seeds) to increase the production of secondary metabolites like polyphenols and phytosterol with anti-microbial and anti-oxidative properties Pulsed electric field treatment may also facilitate the inactivation of pathogenic micro-organisms in raw milk and human milk under preservation of natural antimicrobial enzymes like lactoperoxidase or the anti-microbial lactoferine, which are inactivated in conventional thermal pasteurization processes Food biotechnology and process engineering Food quality and functionality and Food process engineering will jointly investigate this central theme of the process-structure-functionality interactions A further important goal of the ETP is the integration of the food chain from food production all the way to consumption The excellent concentration of research institutes in this field in the Berlin-Brandenburg area ensures that this integration is achieved here at a level that is unique in Germany It is and will be implemented successfully in the Center for Preventive Foods (CPF) and the Innovation Center Health and Nutrition (IGE) 17 B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y 18 ORGANOBALANCE – From Spin-Off to Successful Probiotics Producer Probiotic bacteria have been widely discussed for a number of years, especially in Europe They first became known as relatively unremarkable “useful bacteria” in special yoghurts with rather vague promised effects (like boosting our immune system) Now, however, they increasingly present themselves as probiotic strains with special properties, which are used for various purposes and in different forms These include traditional dairy products – still the main application field –, dietary supplements in tablet form and cosmetic products Prof Dr Christine Lang CEO OrganoBalance GmbH lang@organobalance.de What was originally conceived as a means of promoting intestinal health is now increasingly subjected to scientific scrutiny to understand the underlying mechanisms In some cases probiotics have been developed as a form of preventive medicine Studies have been published showing that certain probiotic strains can be used successfully to alleviate the symptoms of the bowel disease Morbus Crohn or to alleviate cold symptoms and make colds clear up more quickly As an illustration of our work in this field, we would like to present a project here whose development is already advanced In close cooperation with BASF Future Business GmbH, ORGANOBALANCE has succeeded in identifying and describing a naturally occurring bacterium of the Lactobacillus paracasei species, which selectively recognizes the caries pathogen Streptococcus mutans and binds it In highly sensitive screening assays developed specifically for this purpose by ORGANOBALANCE, we filtered a strain from our own collection of bacteria, which can The New Probiotics When ORGANOBALANCE was founded in 2001, recognize and bind the caries pathogen under many of today’s applications of probiotic cul- the conditions that prevail in the mouth The tures as specific promoters of health still had to Lactobacillus cells function as molecular hooks, be explored The word “probiotic” means simply which attach themselves to the surface of the “for life”, and dates back to the early twentieth mutans cells Mutans cells masked in this way century when scientists noticed that the regular can no longer adhere to the teeth as microconsumption of food fermented with lactic acid aggregates, where they usually embed thembacteria brought health benefits This is what selves using self-generated mutan, if sugar convinced ORGANOBALANCE that there was still is present, and produce cariogenic acids The much to be discovered about the real benefits of mutans bacteria can thereby be gently and probiotics and that naturally occurring probiotic effectively removed from the mouth (for examstrains probably offer enormous potential for ple, during teeth-brushing) without harming other oral flora development and benefits for consumers Therefore we began to evaluate the large variety of naturally occurring “good micro-organisms” systematically and built our own collection of strains of micro-organisms, specializing in foodgrade lactic acid bacteria and yeasts, which has been expanded continuously for fifty years In recent years we have used innovative screening methods and raster scans to identify new strains, characterize them and then develop them to product maturity In some cases these efforts have led to completely unexpected and innovative applications Probiotics and the Health Claims Regulation Consumer-protection regulation requirements mean that it is of utmost importance for this new generation of probiotics to be selected according to their function and effects if they are to be brought to market In Europe, health-related claims made for functional components in foods must be tested and evaluated under the European Health Claims Regulation This means that all products for which health-related claims are asserted must have proven their relevance for the health benefit in question in efficacy studies Terminology like “supports”, “regulates” or B i o T O P i c s _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y Figure Scanning EM: Photo of a co-aggregate of Lactobacillus and Streptococcus mutans (Copyright: BASF SE) “improves the immune system” will no longer be permitted unless This makes us a reliable and innovative cooperation partner for the relevant company can present intervention studies that prove the manufacturing industry in the field of R&D One example is the claim and hence the efficacy of the component concerned our strategic partnership with BASF, with whom we have coopThe success of these complex and expensive intervention studies erated successfully in a range of projects since 2002 We are depends on being able to perform step-by-step selection pro- engaged in many other development projects, some of which are cesses during product or active ingredient development until the at laboratory and others already at pilot stage, in close coopbest candidate is found (a standard procedure in drug develop- eration with medium-sized and large companies in Germany, ment) From the large number of existing strains, ONE is thereby Europe and North America eventually selected that exhibits the desired properties At this stage, the candidate in question will already have proven its In these projects, we use synergies in order to bring together the efficacy in in vitro studies and possibly in animal models too expertise and the proprietary bacterial strains of ORGANOBALANCE ORGANOBALANCE uses this search strategy to filter out the “dia- with the market and product know-how of our partners as effecmond” from a large collection of wild-type strains systematically tively as possible ORGANOBALANCE thereby also makes available by ever more stringent test procedures We demonstrated in ini- its know-how in process development and formulations Since tial assays that it is possible using this method to prove conclu- 2007, we have also been able to offer pilot production facilisively the effect-related properties identified at laboratory level ties With 150 liters of fermentation and drying capacity, we can as an effective principle in animal studies and in studies using provide product batches for testing purposes ORGANOBALANCE is test subjects, thus paving the way to market maturity As a new consequently well placed to begin producing its own cultures form of application, the active strains are also eligible for patent protection For the coming period, we also see great development potential for specific functional natural components or strains, especially in ORGANOBALANCE Markets and Fields of Business the fields of nutrition and preventive medicine Micro-organisms Using its own collection of strains and its specially developed traditionally used in foods, such as lactobacillae and yeast, which OASSYS® screening technology, ORGANOBALANCE has succeeded in have GRAS (generally recognized as safe) or QPS (qualified pretapping the potential of new effective micro-organisms for many sumption of safety) status, therefore have a very good chance of areas of application reaching consumers soon Alongside new strains of probiotic bacteria for use in cosmetics During the next twelve to eighteen months, we expect to see the (active agents derived from lactic acid bacteria that specifically first of our products (“Invented in Berlin”) to come on the market stabilize and regenerate the protective micro-flora of the skin), – perhaps with the field of dental care taking the lead our developments include strains for food applications, such as an antagonist to combat caries-generating bacteria or the stomach germ Helicobacter pylori, as well as probiotics for animal health ORGANOBALANCE started out as a spin-off of Technische Universität Berlin Today, the company has 28 employees and is consciously customer-oriented We predominantly conduct projects in the form of license models 19 Paving the way from idea to proof of concept to commercial success TOP 50 is a joint project of Freie Universität Berlin, Charité - Universitäts­ edizin m Berlin, the University of Potsdam and BioTOP Berlin-­ randenburg It is B devoted to intensifying technology transfer in the life sciences TOP 50 is focusing on the decisive step of proof of concept The conversion of new scientific insights into innovations often fails because individual projects are not developed far enough or proof of concept is not achieved, so that the concept is not adopted by industry We help to close this gap between fundamental and applied, commercially oriented research and development TOP 50 is aimed at scientists who are planning to commercialize their scien­ ific projects in the form of a spin-off, cooperation with a t company or by licensing www.biotop.de/top50/ ... Berlin University of Technology Institute of Food Biotechnology and Food Chemistry Department of Food Biotechnology and Food Process Engineering dietrich.knorr@tu-berlin.de Food Processing The... of research for which the bioregion BerlinBrandenburg has strong credentials The close links that exist here between genome research, molecular and clinical nutrition research and plant biotechnology... personalizing food To generate tailor made foods, it is essential to understand the relationships between food and food component processing and the structures and functions affected This research