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Morning Short Course

Systems Biology: A Molecular Nutrition Perspective 

Monday, February 10, 2014 | 8:30 - 11:30 am | Moscone North Convention Center | San Fransisco, CA 


The health of people is highly influenced by genome-environment interactions and the biggest interaction is through diet. Therefore, genetic variability and diet variability concur to create highly specific environments in which diseases develop and drugs acts. It is more and more obvious that diet is a key variable to prevent and cure multifactorial diseases. In this scenario, is becoming of fundamental importance to understand how different population interact with food (different geo-political areas have very different habit) and how genome reacts to food. The main door of food to our molecular environment is through intestine, where we host more than 1 kg of bacteria, the so called microbiome. Understanding how the individual variability in microbiome influence micronutrient absorption and their consequent interaction with our molecular processes is another fundamental step in including the effect of diet in health maintenance. Finally, the main metabolic processes affected by nutrients are also involved in many diseases and their understanding in relation to diet can open new perspective in the treatment of these diseases. Unfortunately, considering diet as a key player in understanding diseases the complexity of the systems under investigation grows even further with respect to the usual systems biology problems. Therefore innovative computational systems approaches are absolutely essential to manage the complexity. The course will cover the intervention studies to understand population variability with respect to diet, the microbiome studies to deal with nutrient absorption, the molecular mechanism of metabolic processes related to nutrients and the computational techniques that could be used in these contexts.


Talk Title to be Announced

Patrick J. Stover, Ph.D., Professor and Director, Division of Nutritional Sciences, Cornell University

Understanding the “variability in individual responses” to dietary exposures and its relationship to human health and performance continues to be one of the major challenges in the nutritional sciences, including the establishment of population-based dietary recommendations and public health guidelines. Understanding the interactions among nutrients and other bioactive food components, human genetic variation and epigenetic variation is fundamental to elucidating inter- and intra-population differences in responses to diets. The design of physiologically relevant model systems and experimental approaches for studying the connections between one-carbon metabolism and cancer in heterogeneous human populations will be addressed. 


Experimental Designs for Systems Nutrition Research

Jim Kaput, Ph.D., Head, Clinical Translation Unit; Delta Vitamin Study Team1, Systems Nutrition and Health Unit, Nestle Institute of Health Sciences

Although systems biology concepts and technologies are beginning to alter experimental design and analyses, research conducted in the 21st century continues to focus on physiological effects caused by providing an individual nutrient to groups of individuals with analysis of a small number of biomarkers. Similarly, geneticists focus on associating an individual polymorphism in a gene to a complex biological process, which typically is a disease. Genome wide association studies (GWAS) rely upon mathematical tools and criteria that analyze the association of multiple but independently-tested SNPs with some complex phenotype.

We are developing strategies for analyses of individual data (n-of-1) for identifying metabolic groups in children ages 6 to 14 in the Delta Obesity Vitamin Study. Our approach analyzed for patterns of plasma and erythrocyte metabolites. The data from n-of-1 studies were aggregated and used to analyze population level results: differences or similarities between sex, by age, by geographic location, or other dichotomous variables. A global protein – protein interaction network was analyzed by topological partitioning with enrichment analysis that grouped functionally related genes. Three modules within this global network contained SNPs that differed statistically between groups defined by patterns of metabolite levels. Two of these modules were involved in digestion and absorption functions and immune functions. Plasma proteins involved in immune functions were also correlated with these patterns of metabolites that better defined the physiological status of the study participants. This systems approach may be a model for analysis of other complex phenotypes.

1This study was a collaboration between scientists at the:
USDA Obesity Research Prevention Research Unit (Little Rock, AR, USA),
The Division of Personalized Nutrition and Medicine of the FDA/National Center for Toxicological Research (Jefferson, AR, USA),
The Boys, Girls, Adults Community Development Center (Marvell, AR USA),
The Department of Pediatrics, Faculty of Medicine of RibeirãoPreto, USP ,RibeirãoPreto (SP, Brazil), Department of Mathematics, University of Trento, Italy and
The Microsoft Research-University of Trento Centre for Computational and Systems Biology (Rovereto, Italy)
Nestle Institute of Health Sciences (Lausanne, Switzerland)


Computational Approaches for Systems Nutrition and Network Analysis

Professor Corrado Priami, Ph.D., Computer Science, The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI)

Computational approaches that are needed for systems nutrition can be composed in pipelines that start from data collection (including omics data, clinical markers, diet and life style) passing through data analysis and mining till simulation and generation of biological hypothesis to better design new intervention studies or biological experiments. We will present one of such pipelines centered around network analysis and pruning to identify the relevant modules for the phenotype under investigation. Once these modules are identified in a data-driven way, they are functionally annotated and possibly dynamically simulated to see how they behave over time. Finally, the results of these in silico experiments are interpreted for the generation of new hypotheses.


Jim Kaput, Ph.D., Head, Clinical Translation Unit; Delta Vitamin Study Team1, Systems Nutrition and Health Unit, Nestle Institute of Health Sciences

JimKaputJim Kaput is the Head of the Clinical Translation Unit in the newly created Nestle Institute of Health Sciences (Nestle Institute Health Sciences). His immediate past position (11.2007 to 7.2010) was as Director of the Division of Personalized Nutrition and Medicine at the U.S. FDA’s National Center for Toxicological Research (Jefferson, AR). He is a member of the Executive Committee of NuGO (Nutrigenomics Organization – www.nugo.org) and its Micronutrient Genomics Project Committee (http://www.nugo.org/micronutrients). He also contributes to the international Human Variome Project (www.humanvariomeproject.org). Dr. Kaput received his PhD from Colorado State University in Biochemistry and Molecular Biology. He spent 5 years as a postdoctoral fellow and assistant professor at the Rockefeller University in the laboratory of GÜnter Blobel, the 1999 Nobel Laureate in Physiology and Medicine. Dr. Kaput was a staff and Biochemistry faculty member at the University of Illinois College of Medicine and Director of the Northwestern University Biotechnology Laboratory for 2 years. He also was science advisor for international activities at the European Nutrigenomics Organization (NuGO), Coordinator of Science and Administrative Activities for the NCMHD Center of Excellence in Nutritional Genomics at the University of California Davis, and Assistant Professor in the Department of Surgery at the University of Illinois Chicago (UIC). He co-founded 2 nutrigenomic biotechnology companies (1998 J and 2002), one of which merged with a publically traded company. He received a Fulbright Senior Specialist Program in Public/Global Health for 2006 through 2011 and visited Brazil in 2007. This program is administered through the Bureau of Education and Cultural Affairs in the U.S. Department of State and the Council for International Exchange of Scholars.

Patrick J. Stover, Ph.D., Professor and Director, Division of Nutritional Sciences, Cornell University

PatrickStoverPatrick J. Stover, Ph.D. is Professor and Director of the Division of Nutritional Sciences at Cornell University. He graduated from Saint Joseph’s University with a BS degree in Chemistry and was awarded the Molloy Chemistry Award at graduation. He received a PhD degree in Biochemistry and Molecular Biophysics from the Medical College of Virginia and performed his postdoctoral studies in Nutritional Sciences at the University of California at Berkeley. The Stover research group investigates the chemical, biochemical, genetic and epigenetic mechanisms that underlie the relationships between one-carbon metabolism and human pathologies including neural tube defects, cardiovascular disease and cancer. Specific interests include the regulation of folate-mediated one-carbon metabolism and genome expression and stability, the molecular basis of the fetal origins hypothesis, development of mouse models to elucidate mechanisms of folate-related pathologies, and translational control of gene expression. Our current focus is on the role of nuclear one-carbon metabolism in de novo thymidylate synthesis in maintaining genome integrity, and its regulation by SUMOylation and UV radiation. We have developed mouse models of altered one-carbon metabolism by gentically manipulating the expression of folate-associated genes to determine the effects of altered one-carbon supply on cellular methylation potential, nucleotide biosynthesis and colon cancer susceptibility. An overarching goal of these studies is to differentiate the contributions of folate-dependent de novo nucleotide biosynthesis and folate-mediated cellular methylation in folate-associated pathologies. Patrick Stover also teaches two classes for graduate students: NS7040, Grant Writing and NS6200 Translational Research and Evidence-based Policy and Practice in Nutrition. Patrick Stover received a MERIT award in 2012 from NIDDK-NIH. In 1996 he received the Presidential Early Career Award for Scientists and Engineers from President Clinton, the highest honor bestowed by the U.S. government on outstanding scientists and engineers beginning their independent careers. He received the ERL Stokstad Award in Nutritional Biochemistry from the American Society for Nutritional Sciences in 1999 and has been selected as an Outstanding Educator four times by Cornell Merrill Presidential Scholars. He is a current member of the National Academies of Sciences’ Food and Nutrition Board. He serves on the editorial board for the Annual Reviews of Nutrition, the Journal of Biological Chemistry and the American Journal of Clinical Nutrition.

Professor Corrado Priami, Ph.D., Computer Science, The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI)

PriamiCorrado Priami obtained his Laurea and PhD degrees in Computer Science at the University of Pisa, visited as associate researcher at the laboratory LIX, École Politechnique, Paris (1995) and the École Normale Supérieure, Paris under an EC Marie Curie TMR grant (1996). He was a researcher and associate professor at the University of Verona (1997-2001). Currently, he is a professor of Computer Science at the University of Trento. The results of his PhD thesis on stochastic pi- calculus were the basis for the foundation of the Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI), of which he is the President and CEO. Those same results, besides constituting the scientific foundation of COSBI, are recognized as fundamental in the field of systems biology by an expanding international community, which is using them to model the behavior of biological systems (the CMSB conference is a milestone of this). He was member of the expert group on the EU 7th FP of the CRUI and has participated in many projects promoted by the European Commission for the advancement of emerging areas of research. He regularly serves on the evaluation committees for projects presented by the European Commission, is an anonymous reviewer for many international journals, and serves in the review panels of the Science Foundation Ireland for institutes of systems biology and of the Netherlands Organisation for Scientific Research. He is a member of the Scientific committee of the Fondazione Veronesi. His research covers computational methods for the modelling, analysis, and simulation of biological systems, programming languages, and formal computational theories. He published over 130 papers in international journals and conferences, given more than 40 invited talks and lectures at conferences and universities around the world, participated in the program committees for 21 international conferences (ten of which he was chair), is a member of three steering committees of international conferences (of which one he is president), is editor-in-chief of the international journal Transactions on Computational Systems Biology and member of the editorial board of the international journal Bioinformatics Research and Applications. He founded the international conferences “Computational Methods in Systems Biology (CMSB),” which is continuing to grow, and “Converging Sciences,” whose success has been described by many international journals. He was a member of ISTAG-FET (Information Society Technologies Advisory Group - Future and Emerging Technologies) of the European Commission.

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