Scientific Program

Day 1

KEYNOTE SPEAKERS
  • A model explaining protracted weight loss after Roux en Y gastric by-pass bariatric surgery

    King's College
    United Kingdom
    Abstract

    Despite evidence that Roux en Y gastric by-pass (RYGB) does not generally lead to a sustained decrease in dietary intake or appetite loss, this form of treatment is the most effective method of producing sustained weight loss in morbidly obese subjects. Animal and clinical studies have shown that RYGB induces metabolic changes enhancing energy expenditure at rest and particularly in the post-prandial period, so-called diet-induced thermogenesis (DIT) and also to increased faecal energy loss via both fat and undigested protein. A key question is what is the cause of the enhanced DIT following RYGB? Saeidi et al and Cavin et al. have reported that after RYGB in obese rats, the alimentary limb (AL) becomes hyperplastic and hypertrophic showing up-regulation of the glucose transporter GLUT1 in enterocyte basolateral membranes, also cytoplasmic hexokinase 2 and increased intraluminal metabolism of glucose as demonstrated by 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) positron emission tomography. Sustained weight loss due to Roux en Y gastric bypass surgery (RYGB) may either be the result of improved incretin response to or a change in energy balance. A recent computer model of human glucose absorption and metabolism has been adapted to provide an explanation of both the increased DIT and weight-loss after RYGB. There are three likely mechanisms explaining the RYGB induced sustained weight loss: Increased sensitivity to incretins gastric inhibitory polypeptide GIP and glucagon-like peptide 1 GLP-1; increased leakage of glucose from the splanchnic circulation back into the small intestinal lumen via either trans-cellular route. This results from increased expression of glucose transporters at both the enterocyte basolateral and apical membranes, i.e. GLUT1 and GLUT2, or to inflammation-induced increased paracellular leakage. Overgrowth of facultative aerobic bacteria within the small intestine leads to enhanced luminal conversion of glucose to CO2 with consequent depletion of net energy absorption. The computer model simulates all of the combinations of these conditions and the observed decreases in plasma glucose and insulin concentrations along with increase in post prandial and fasting metabolic rates following RYGB. A combination of all three factors is likely to be the explanation for the success of RYGB. This raises the interesting consideration as to whether a non-surgical intervention which simulates these effects might be as efficacious as RYGB in producing sustained weight loss in morbidly obese subjects.

    References

    1. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Nestoridi E, Kvas S, Kucharczyk J, Stylopoulos N. Endocrinology. 2012 May; 153(5):2234-44 PMID: 22416083 DOI: 10.1210/en.2011-2041

    2. Diet-induced thermogenesis and respiratory quotient after Roux-en-Y gastric bypass surgery: a prospective study. Faria SL, Faria OP, Cardeal Mde A, Ito MK, Buffington C. Surg Obes Relat Dis. 2014 Jan-Feb; 10(1):138-43 PMID: 24507080 DOI: 10.1016/j.soard.2013.09.020

    3. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Science. 2013 Jul 26; 341(6144):406-10 PMID: 23888041 DOI: 10.1126/science.1235103

    4. Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy. Cavin JB, Couvelard A, Lebtahi R, Ducroc R, Arapis K, Voitellier E, Cluzeaud F, Gillard L, Hourseau M, Mikail N, Ribeiro-Parenti L, Kapel N, Marmuse JP, Bado A, Le Gall M. Gastroenterology. 2016 Feb; 150(2):454-64.e9 PMID: 26481855 DOI: 10.1053/j.gastro.2015.10.009

    5. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states. Naftalin RJ. F1000Res. 2016; 5:647 PMID: 27347379 DOI: 10.12688/f1000research.8299.1

Cancer metabolomics | Diagnostic biomarkers | Analytical-bioanalytical Techniques | Personalised Medicine
Chair
Speaker
  • Speaker
    Evaluating heme flux and function in lung cancer
    Time: 10:30-11:00
    Speaker
    Li Zhang
    The University of Texas
    USA
    Biography

    Li Zhang completed her PhD from UCLA and postdoctoral studies from MIT department of Biology. She is the Cecil H. and Ida Green Distinguished Chair in Systems Biology Science at the University of Texas at Dallas. Professor Zhang’s laboratory has worked on studying heme signaling and function for 20+ years. She has published many original research articles and a book entitled “Heme Biology: The Secret Life of Heme in Regulating Diverse Biological Processes” on this subject. Professor Zhang’s laboratory has also made important contributions in understanding the roles of molecular chaperones in cellular signaling, molecular mechanisms of oxygen signaling, and the actions of neurotoxicants. Recently, Professor Zhang’s lab focuses on investigating heme function in lung cancer. She and colleagues have provided a unifying view of cancer bioenergetics in a review article entitled “A Holistic View of Cancer Bioenergetics: Mitochondrial Function and Respiration Play Fundamental Roles in the Development and Progression of Diverse Tumors,” published in the journal “Clinical and Translational Medicine.”

    Abstract

    Emerging experimental data increasingly show that despite the enhanced glycolytic flux, many types of cancer cells exhibit intensified oxygen consumption or mitochondrial respiration. Even under hypoxia, cancer cells can maintain oxidative phosphorylation at a substantial rate. Heme is a central factor in oxygen utilization and oxidative phosphorylation. It serves as a prosthetic group in many proteins and enzymes involved in mitochondrial respiration. Our recent work showed that non-small-cell lung cancer (NSCLC) cells and xenograft tumors exhibit substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins, and various types of oxygen-utilizing hemoproteins, such as cytoglobin and cytochromes. In contrast, lowering heme biosynthesis and uptake, like inhibiting mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. To further ascertain the importance of elevated heme flux and function in lung tumorigenesis, we use multiple experimental approaches to detect the levels of heme synthesis, uptake, and degradation in an array of NSCLC cell lines and in de novo tumors in genetically engineered mouse models for lung cancer. We also measure oxygen consumption and ATP generation in these cell lines and tumors. These experiments should reveal the degree to which elevated heme flux—heme synthesis, uptake, and degradation—contribute to lung tumorigenesis and how heterogeneity in heme flux contributes to metabolic and bioenergetics heterogeneity in lung tumors.

  • Speaker
    Blood-based metabolomic biomarkers for human neurological disorders
    Time: 11:00-11:30
    Speaker
    Massimo S. Fiandaca
    University of California
    USA
    Biography

    Massimo S Fiandaca, MD, MBA, is a neuroscientist and Associate Professor in the Departments of Neurology and Neurological Surgery at the University of California Irvine (UCI). As Co-director of the Federoff Translational Laboratory and Biorepository (TLaB) at UCI, Dr. Fiandaca is currently focused on blood-based biomarkers related to neurological disorders. Through established local, national, and international collaborations, Dr. Fiandaca and colleagues hope to impact the development of relevant blood-based biomarkers for a variety of conditions affecting the nervous system. Dr. Fiandaca is a board certified neurological surgeon, who retired from surgical practice after 25 years, and returned to full-time academic research and teaching. His past research experiences have focused on direct brain delivery of therapeutics for neurodegenerative disorders and neurooncology, including cellular and tissue transplantation, viral-vector based therapeutic gene delivery, MRI-directed convection-enhanced delivery, and nanoliposomal therapeutics.

    Abstract

    For many human maladies, especially neurodegenerative disorders (e.g., Alzheimer’s disease, AD, and Parkinson’s disease, PD) the ability to predict disease risk during asymptomatic stages is essential for earlier and more efficacious interventions. Blood-based biomarkers for AD (and PD), once defined and validated, may facilitate the participation of at-risk asymptomatic individuals in therapeutic clinical trials, and thereby increase the potential for successful prevention and/or disease modification. In conditions such as mild traumatic brain injury (mTBI), relevant blood bio-signatures could provide unbiased diagnostics that significantly improve clinical decision-making and improved treatments. Blood-based metabolomic biomarkers may offer such diagnostic and therapeutic potential in both AD and mTBI, as evidenced by our recent work. In this seminar, I plan to discuss our group’s approaches to blood-based metabolomic biomarker development and present results from our most recent metabolomic investigations related to AD and mTBI. We are encouraged by the potential provided by both untargeted and targeted metabolomic platforms in defining annotated species that are germane to the respective clinical conditions. We also provide caution to those exploring this area of research since there are many confounding factors that need close scrutiny in an effort to maximize clinical utility.

  • Speaker
    Metabolomics on mouse models of disease for personalized medicine
    Speaker
    Preeti Bais
    The Jackson Laboratory for Genomic Medicine, USA
    USA
    Biography

    Preeti Bais is a Scientist at Jackson Lab’s new research institute- JAX Genomics Medicine (JGM). It is an independent, nonprofit organization focusing on mammalian genetics research to advance human health. She holds a PhD degree in Bioinformatics and Computational Biology. She has worked on projects involving metabolomics analysis of Human Embryonic Stem (hES) and Induced Pluripotent Stem (IPS) cells based assays for drug toxicity screening, autism biomarker detection using blood samples, mouse models of neuromuscular degeneration and cancer drug efficacy testing using orthotropic mouse models triple negative breast cancer.

    Abstract

    Metabolomics is a newer omics technology that can help in generating a more comprehensive view of a biological system when combined with the genomic, transcriptomic and proteomic technologies. In this seminar, I will discuss the bioinformatics infrastructure that we have developed at Jackson Laboratory to perform mass spectrometry based metabolomics experiments on mouse based studies. I will highlight some case studies where I have used metabolomics in mouse models of neuromuscular degeneration and patient derived xenograft (PDX) for cancer studies and personalized medicine. Charcot-Marie-Tooth (CMT) disease encompasses a genetically heterogeneous class of heritable motor and sensory neuropathies that result in axonal degeneration in the peripheral nervous system. Charcot-Marie-Tooth type 2D (CMT2D) is caused by dominant mutations in Glycyl tRNA Synthetase (GARS). Samples from the spinal cord of GARS mutant mice and littermate control animals were compared using mass spectrometry based metabolomics. The changes associated with GARS mutations suggested possible treatment strategies through supplementation. In another case study, Gas Chromatography Mass Spectrometry (GCMS) based analysis was used to derive a metabolic signature of triple negative breast cancer (TNBC) by comparing the metabolites present in three study arms of patient-derived xenograft (PDX) mouse urine. This analysis not only suggested metabolic uniformity of the JAX mice but also showed cancer specific changes in the vehicle (tumor with no treatment) arm, known drug side effects in the treatment arm (tumor engrafted and treated) and the age related changes in the pure (no tumor no treatment) arm.

  • Speaker
    Comprehensive LC-MS reference library: Construction strategy and application in metabolic profiling and metabolomics
    Speaker
    Ilana Rogachev
    Weizmann Institute of Science
    Israel
    Biography

    Ilana Rogachev is a trained Analytical Chemist, an expert in Metabolomics, specializing in the analysis of natural products using LC-MS and GC-MS instruments. Her knowledge in the analysis of complex plant extracts and in structural identification of natural products formed the basis of the chosen experimental methods and the analytical rationale behind the computational algorithms used to create the WEIZMASS library.

    Abstract

    Unambiguous metabolite identification is an essential but yet unresolved problem in mass spectrometry-based (MS) metabolomics assays. It is particularly critical in studies of rich metabolic matrices such as those present in plant extracts. Generating a comprehensive mass spectra library from highly pure reference compounds isolated from an extensive repertoire of plant species is currently the most reliable strategy for advance in MS based identification of natural products. To address the issue of generating large MS libraries in a high-throughput manner, two computational pipelines were developed: one allows an automated construction of a reference library from LC-MS injections of authentic chemical standards and the other, termed ‘MatchWeiz’, allows for an efficient and accurate matching of high resolution experimental LC-MS data to the reference library data. We applied the presented methods by injecting a comprehensive collection of several thousands of plant secondary (specialized) metabolites using a UPLC-qTOF MS in the MSE mode in order to generate a large and structurally diverse MS spectra library, termed ‘WEIZMASS’. In this presentation, I will demonstrate the experimental methods used for the rapid generation of the WEIZMASS library: the main considerations during sample preparation and the choice of instrumentation parameters for the rapid construction of such a large MS reference library. I will highlight the building blocks of the software pipelines used and, present the chemical rationale behind the computational algorithms. Finally, I will demonstrate the application of the WEIZMASS library for identification of secondary metabolites in different plant extracts.

  • Speaker
    Stable isotope-assisted metabolomics of Fusarium head blight on wheat
    Time: 13:30-14:00
    Speaker
    R. Schumacher
    University of Natural Resources and Life Sciences (BOKU)
    Austria
    Biography

    Rainer Schuhmacher is an Associate Professor at University of Natural Resources and Life Sciences (BOKU), Vienna where he is heading the working group Metabolomics and Bioactive Compounds. His research focuses on LC-HRMS and GC-MS based metabolomics of microbes and plants with a special focus on the interaction between these living organisms. He received his degrees in Chemistry at University of Konstanz, Germany and Vienna University of Technology, and in 2009 he completed his Habilitation in Analytical Chemistry at BOKU University, Vienna. He is co-author of more than 120 SCI publications.

    Abstract

    Metabolomics studies show great potential to provide an improved understanding of the molecular mechanisms underlying plant diseases such as Fusarium head blight (FHB) on wheat. Here, we present the successful combination of LC-HRMS based global 13C labeling- & 13C tracer techniques to probe both the attack of the mycotoxigenic fungus Fusarium graminearum as well as the metabolic response of near isogenic wheat lines, differing in a major resistance QTL against FHB. To do so, parent and corresponding wheat NILs were cultured in the greenhouse and treated with F. graminearum spores at anthesis. In addition, custom-tailored, globally 13C-labelled wheat plants of the resistant and susceptible parent lines were grown as a reference in a tailor-made labeling chamber. To further elucidate the phenylalanine (Phe) - and tryptophan (Trp)- derived submetabolome, wheat ears were also treated with U-13C phenylalanine or U-13C tryptophan (Trp) under control- and infection conditions. LC-HRMS and subsequent data analysis clearly revealed some 1.000 metabolites in the tested biological samples. Among those ca. 100 and 70 were found to be derived from the metabolic precursors Phe and Trp, respectively. Substance with levels, which were significantly affected by Fusarium have been further investigated for their putative role in QTL mediated resistance against FHB. The abundance of various substance classes differed significantly between the tested wheat lines with respect to both the timing of formation and relative amount. Our results for hydroxycinnamic acid amides, phenolic acids, flavonoids and lignans suggest that different molecular mechanisms contribute to defense and resistance against FHB. In this talk, I will present the isotope-assisted metabolomics protocols which we have developed and how we have investigated defense responses and resistance mechanisms of wheat against Fusarium head blight.

  • Metabolic systems analysis with multi-omics data
    Time: 14:00-14:30
    Speaker
    Fumiko Matsuzaki
    Kyushu University
    Japan
    Biography

    Fumiko Matsuzaki is a Molecular and Systems Biologist with a PhD in Medical Science from Kyushu University, Japan. Her work has involved proteomics, metabolomics and molecular and biochemical approaches to the investigation of cancer metabolism, xenobiotic metabolism and membrane trafficking. Recent developments in omics technologies led her to start computational work with bioinformatics and mathematical approaches to take advantage of omics data. She aims to deliver practical methods to decipher complicated biological systems.

    Abstract

    Advances in omics technologies have enabled us to measure a large number and variety of molecular components of cells. This should enormously assist in our understanding of complex biological phenomena and the improvement of more quantitative omics methods will accelerate this understanding. However, effective ways to take advantage of such data have not yet been developed. A need exists for an analytic methodology to extract biological characteristics, as well as for more sophisticated quantification methods to advance our understanding of how organisms achieve highly regulated systems. In our current research, we have developed a new technology termed in vitro proteome–assisted multiple reactions monitoring for protein absolute quantification (iMPAQT) to measure the absolute quantities of all human proteins. With the use of iMPAQT, we have measured the absolute quantities of almost all metabolic enzymes in human cells and uncovered the weights of each node in human metabolic networks. In addition, we have developed a new computational method based on biochemical systems theory to integrate the absolute quantities of metabolic enzymes, as well as those of metabolites measured by metabolomics, experimentally available fluxes and metabolic network structure. It is now possible to estimate each flux, calculate sensitivities of fluxes and metabolite concentrations with respect to the concentration of each enzyme, and simulate metabolite concentrations under some perturbations. In order to extend the combined approach of large scale quantification and computational analysis, in our institute we have set up the Research Center for Transomics Medicine, where proteome, transcriptome, metabolome and other omes can be measured. Furthermore, we are now attempting to integrate multi-omics data and analyze insulin action on metabolism in the liver as a pilot study. We expect that a further development of this approach will lead to comprehensive understanding of how the metabolic network system or various biological systems are regulated and will establish a new leading edge of modern biology.

  • Speaker
    High resolution metabolomics to identify novel biomarkers in corticosteroid resistant asthmatic children
    Time: 14:30-15:00
    Speaker
    Youngja park
    Korean University
    South Korea
    Biography

    Youngja Park obtained an M.S. and Ph.D in Pharmacology and Toxicology under Dr. James P. Kehrer at the University of Texas at Austin in 1990. She previously had worked as an Assistant Professor in the Department of Medicine and as the Assistant Director of the Clinical Biomarkers Laboratory at the Emory University School of Medicine since 2013. In Emory University, she developed LC-MS based metabolomics pipelines to identify novel biomarkers and the pathways associated with diseases. She published the number of metabolomics papers including Science and Journal of Allergy and Clinical Immunology. Currently she moved back to College of Pharmacy, Korea University where she has built metabolomics core facility after years of experience in research, evaluation and teaching both in hospital and education institutions. Her career goal is to identify the novel biomarkers and develop the sensors in early diagnoses of disease.

    Abstract

    Corticosteroid (CS) treatment is the preferred anti-inflammatory treatment for adults and children with asthma. However, a subset of patients fails to respond to combined systemic and inhaled CS treatment despite very high doses and prolonged treatment. Due to the uncertainty of the molecular mechanism for CS-resistant asthma, this study is aimed at discovering diagnostic biomarkers for early identification of children resistant to CS. High resolution metabolomics (HRM) was performed on plasma and urine samples from CS-respondent and CS-non-respondent children to determine putative biomarkers related to CS resistance. The metabolic phenotypes of CS-responders and CS-non-responders were analyzed using bioinformatics including Manhattan plot with False Discovery Rate (FDR), Hierarchical Cluster Analysis (HCA), Kyoto Encyclopedia Genes and Genomes (KEGG) and Mummichog pathway analysis. The Manhattan plot with false discovery rate determined 1894 metabolites in plasma and 30 metabolites in urine significantly altered between CS-responders and CS-non-responders. The important metabolites annotated were S-adenosylmethionine (439.1395 m/z, [M+ACN+H]+) and S-adenosylmethionine (378.1448 m/z, [M+Na]+) in plasma as well as ?-glutamylcysteine (236.06 m/z, [M+S(34)+H] +) and Cys-Gly, (253.06 m/z, [M-NH3+H]+), reduced FMN (517.0794 m/z, [M+NaCl]+). Thus, the metabolites in glutathione metabolism were altered significantly regarding CS resistance. The identified biomarkers in urine of asthmatic children would be extremely beneficial not only for early detection, but also in the development of therapies aimed at preventing the irreversible airway damage and lung function decline associated with CS resistance in severe asthma among children.

  • Speaker
    Automated annotation of the wheat metabolome during Fusarium infection using stable isotopic labeling and custom-tailored data processing workflows
    Speaker
    Christoph Bueschl
    University of Natural Resources and Life Sciences
    Australia
    Biography

    Christoph Bueschl is a Post-doctoral Researcher at Metabolomics group at IFA-Tulln with expertise in automated data processing of LC-HRMS data. He is specialized in data evaluation and software development of stable isotope assisted and LC-HRMS based untargeted metabolomics experiments as well as stable isotope assisted tracer experiments that probe the secondary metabolism of either endogenous or exogenous secondary metabolites in biological systems. His developed software tools are actively being used, steadily improved and extended with new functionality and applied in various projects and co-operations. Besides data processing of LC-HRMS data, one of his research interests is statistical evaluation of large datasets especially in the area of metabolomics research.

    Abstract

    Fungi of the genus Fusarium infect crop plants thereby causing plant diseases and contamination of food with its toxic secondary metabolites so-called mycotoxins. To characterize the plant’s metabolic defense mechanisms to Fusarium infection, we have developed several analytical protocols accompanied by custom-designed automated data processing tools. The first workflow, entitled all extract, is designed for the detection of all LC-HRMS accessible metabolites of wheat. It uses either uniformly 13C-labeled or 15N-labeled wheat reference material, which has been grown in-house and has an isotopic enrichment of ~99%, for metabolite detection and annotation (~1.000 carbon- and ~300 nitrogen-containing metabolites). Moreover, the 13C-labeling step enables metabolome-wide internal standardization thereby improving relative quantification and subsequent statistical comparison of the experimental groups. A second workflow, named TracExtract, allows probing the metabolism of exogenous or endogenous 13C-labeled tracer compounds in wheat plants and reports only biotransformation products that the plant has produced from the respective tracer. Using this approach, uniformly 13C-labeled phenylalanine and tryptophan tracers have been used to annotate respective tracer-derived wheat biotransformation products (120 and 60 respectively). This annotation is especially helpful since many of the already known defense-related metabolites in wheat are descendants of these two tracer compounds. Furthermore, the tracer approach was successfully used to investigate the plant’s detoxification mechanisms of Fusarium graminearum most potent mycotoxin deoxynivalenol. A total of nine mostly novel detoxification products were detected. Finally, all information about the wheat metabolites is aggregated thus describing each detected metabolite with its total number of carbon and nitrogen atoms and if it is derived from phenylalanine or tryptophan. This untargeted annotation is an invaluable resource for further investigation of wheat-Fusarium interaction on a metabolic level and enables a more focused investigation of potential novel defense-related metabolites.

  • Building and optimizing multi-enzyme in vitro cascade reactions
    Time: 15:45-16:15
    Speaker
    Nicholas Harmer
    University of Exeter
    United Kingdom
    Biography

    Nicholas Harmer completed his PhD in the laboratory of Professor Sir Tom Blundell in Cambridge, UK, researching the structure and interaction of fibroblast growth factors, their receptors, and heparin. Following this, he took a Post-doctoral position in Cambridge, investigating the structure and function of a range of signaling proteins and bacterial enzymes. He then moved to AstraZeneca R&D Mölndal, Sweden, where he worked as a Structural Biologist in Drug Discovery. In 2007, he established his own laboratory at University of Exeter, UK. His research work focusses on Synthetic Biology and Drug Discovery applications for neglected diseases. His main interest is in understanding enzymes more deeply, and in exploiting this understanding to develop useful chemicals and biochemical. In 2017, he moved to Living Systems Institute, Exeter.

    Abstract

    Biocatalysis is becoming increasingly attractive for the development of more efficient and cleaner chemical synthetic processes. The combination of multiple enzyme steps for cascade reactions allows for attractive one-pot processes with reduced operating costs. While the use of whole-cells have a number of advantages for these reactions, the competing needs of the cell and limited transport across the cell membrane can result in a low final product concentration. In contrast, the use of isolated enzymes allows reactions to be easily controlled, with the use of stable enzymes such as those from thermophiles offering economically competitive processes. For the construction of novel enzymatic cascade reactions, there is a need for well-defined modular enzyme building blocks that can be quickly assembled for new reactions. Carboxylic acid reductase (CARs) is a relatively undeveloped class of enzyme which meets a demand in synthetic chemistry for a green and regiospecific route to aldehydes from their respective carboxylic acids. A thorough biochemical characterization of four new CARs provides insight into the operating parameters of these enzymes, while the integration of a CAR into a seven enzyme in vitro cascade reaction demonstrates their potential for green chemistry. Mathematical modeling of the cascade allows for a detailed understanding of the reaction and gives opportunity for its optimization with respect to flux and cost. Our work highlights the virtue of thorough enzyme characterization, and of modeling reactions, to deliver new understanding and build robust pathways.

  • Speaker
    Pharmacometabolomics-guided pharmacogenomics in precision medicine
    Time: 16:15-16:45
    Speaker
    Theodora Katsila
    University of Patras
    Greece
    Biography

    Theodora Katsila currently serves as a Senior Research Fellow and academic scholar. Her research work focuses on “Spans pan-omics strategies coupled to information technologies toward better-informed decision-making and genotype-to-phenotype correlations”. Sharing both academic and industrial research experience, she has a multidisciplinary expertise.

    Abstract

    Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of pharmacometabolomics-guided pharmacogenomics. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences) with information technologies to facilitate data analysis as well as sense and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective multi-omics studies coupled to information technologies allow for data reproducibility and robustness in genotype-to-phenotype correlations.

    Reference: Katsila et al. EBiomedicine (2016)

Day 2

KEYNOTE SPEAKERS
  • Heme: A key metabolite impacting diverse physiological and pathological processes

    The University of Texas
    USA
    Biography

    Li Zhang completed her PhD from UCLA and postdoctoral studies from MIT department of Biology. She is the Cecil H. and Ida Green Distinguished Chair in Systems Biology Science at the University of Texas at Dallas. Professor Zhang’s laboratory has worked on studying heme signaling and function for 20+ years. She has published many original research articles and a book entitled “Heme Biology: The Secret Life of Heme in Regulating Diverse Biological Processes” on this subject. Professor Zhang’s laboratory has also made important contributions in understanding the roles of molecular chaperones in cellular signaling, molecular mechanisms of oxygen signaling, and the actions of neurotoxicants. Recently, Professor Zhang’s lab focuses on investigating heme function in lung cancer. She and colleagues have provided a unifying view of cancer bioenergetics in a review article entitled “A Holistic View of Cancer Bioenergetics: Mitochondrial Function and Respiration Play Fundamental Roles in the Development and Progression of Diverse Tumors,” published in the journal “Clinical and Translational Medicine.”

    Abstract

    Heme, iron protoporphyrin IX, plays fundamental roles in virtually all living organisms. As a main source of iron for many pathogenic bacteria and fungi, heme impacts their virulence. In mammals, heme is required for the proper functioning of most, if not all, cells and organs. Accumulating evidence increasingly shows that altered heme flux and function contribute to the pathogenesis of many diseases, including common diseases such as cancer and Alzheimer’s disease. This broad involvement of heme in human conditions stems in part from its central role in oxygen utilization and metabolism. Further, heme serves as a regulatory and signaling molecule that directly modulates many fundamental molecular and cellular processes by acting on diverse regulatory proteins impacting many physiological and pathological processes, such as tumorigenesis and neural development. I will review how heme modulates the activity of certain representative regulatory proteins, such as transcriptional regulators and histone demethylases. I will also provide recent experimental data implicating the roles of altered heme flux and metabolism in lung tumorigenesis and neuronal dysfunction.

Plant & Environmental Metabolomics | Metabolites| Metabolomics in diseases
Chair
Speaker
  • Speaker
    Modulation and resilience of the metabolome of Pseudomonas graminis, a cloud bacterium, facing H2O2 atmospheric stress
    Time: 11:45-12:15
    Biography

    Anne-Marie Delort is a Senior Scientist at CNRS. She is working at Institute of Chemistry of Clermont-Ferrand in France. In addition to a general background in chemistry and molecular biology, her expertise covers Microbiology and Metabolomics. She specifically studies microbial metabolism in relation with the environment. She has been a pioneer in studying the microbial population in clouds. Recent studies concern the adaptation of microorganisms to atmospheric stresses and the role of microorganisms in atmospheric chemistry and physics. This includes the transformation of organic matter, interaction with oxidants and formation of ice nuclei and cloud condensation nuclei (biosurfactants). Her group is part of MetaboHUB, the French national infrastructure of excellence in metabolomics and fluxomics.

    Abstract

    In cloud waters, microorganisms are metabolically active although they are exposed to very strong stresses, especially due to the presence of reactive oxygenated species, including H2O2 and radicals. In order to understand how microorganisms can modulate their metabolism facing H2O2 stress, we have investigated by a metabolomics approach the response of a Pseudomonas graminis strain, isolated from cloud waters, to hydrogen peroxide exposure. For this purpose P. graminis cells were incubated in microcosms containing artificial cloud waters in the presence or absence of H2O2. Metabolites were extracted at two time points (50 min and 24 h) that were important regarding the evolution of ATP cellular content and H2O2 degradation over time. These bacterial extracts were analysed by LC-MS and 1H-NMR using the Metabolic Profiler® facility (Bruker). Metabolic profiles were converted into matrices and statistical analyses (PCA, PLS-DA) were performed; key markers of this oxidative stress were identified by 2D NMR and LC-MS-Orbitrap. At time 50 min, when H2O2 was still present in the incubations, the bacteria adapted and modulated their metabolome facing this stress. The major metabolic pathways of Pseudomonas graminis (13b-3) impacted by the presence of hydrogen peroxide were the carbohydrate pathway, glutathione, energy, lipid and amino-acid metabolisms. Unexpectedly, the concentration of a few dipeptides containing mainly Ala, Val, Leu (Ile) was also highly modified in the presence of H2O2. These dipeptides are reported here for the first time as biomarkers of oxidative stress. Interestingly, at time 24 h, when H2O2 has been completely biodegraded by the cells, no more significant difference was observed between the metabolites of exposed and non-exposed cells to H2O2. This shows the resilience of this bacterium metabolome after H2O2 stress exposure. These results are discussed in terms of impacts on cloud chemistry.

  • Speaker
    Antihypertensive effects of natural honeybee products: A review
    Time: 12:15-12:45
    Speaker
    Zeliha Selamoglu
    Omer Halisdemir University
    Turkey
    Biography

    Zeliha Selamoglu is a Professor in Medical Biology department of Ömer Halisdemir University, Turkey. She completed her PhD in Biology from Inonu University. She has published over 70 peer reviewed journal articles with over 500 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine. She has served as an Editorial Board Member for many Journals.

    Abstract

    Oxidative stress is associated with increased generation of oxidizing molecules parallel to a significant decrease in the endogenous total antioxidant capacity. It represents an important pathological hallmark in several disorders, including cardiovascular conditions such as hypertension, and atherosclerosis, and neurodegenerative diseases such as Parkinson's disease, and Alzheimer's disease. Naturally occurring antioxidants are largely used as dietary supplements to attenuate oxidative stress in human disease. Honey bee products have attracted clinical interest due to their favorable pharmacological and biological properties, including anti-aging, anti-tumoral, antimicrobial, antioxidant, anti-inflammatory effects. The presence of several important phytochemical classes, such as flavonoids, aromatic acids and phenolic components has been attributed to the beneficial effects of these products. This review evaluates current findings on the antihypertensive properties of honey products and their therapeutic relevance to the clinic.

  • Speaker
    Expression of genes involved in taxol biosynthetic pathway in Taxus baccata L. and application of magnetic- and carbon-based nano-adsorbents for pre-purification of taxol
    Time: 12:45-13:15
    Speaker
    Mohammad Reza Naghavi
    University of Tehran
    Iran
    Biography

    Mohammad Reza Naghavi is an academic member at University of Tehran, Iran. He has published more than 140 research articles in the field of Plant Biotechnology. He has been serving as an Editorial Board Member of four international and national journals.

    Abstract

    This work was undertaken to elucidate the consequences of some environmental cues (?i.e.??? day length, temperature, hours of sunlight and relative humidity) on the expression patterns of TXS, DBAT, BAPT and DBTNBT genes contributed to the ?taxol biosynthetic pathway. Our results indicated that environmental cues have synergistic or antagonistic regulatory roles on transcription activity and taxanes accumulation in yew, though DBAT activity is less influenced, could be accordingly a rate-limiting enzyme. Furthermore, a modified analytic hierarchy process (AHP)?? approach based on refinement assay of ?non-dominated alternatives was employed to monitor ?the most reliable callus maintenance media of T. baccata callus culture?s in terms of five criteria. Our results connoted that L-glutamine-based feeding appears to generate more significant results either for calli growth continuously or taxanes production, while, for stems, both amino acid supplies had fairly equal worth. Meanwhile, considering decolorization efficiency, purity of taxol, recovery and reusability of adsorbents, Fe3O4NPs@GO (50 g/L) in dichloromethane was selected as the best medium for pre-purification of paclitaxel. Finally, based on RSM data, the optimum conditions to simultaneously acquire the maximum EPPR (?94.0%) and ETP (?11.4?%) were recorded as adsorbent dosage of ??37.7 g L–1, sorption temperature of ??30.7°C and agitation power of ?153.1? rpm; and the predictive results were confirmed using experimental rechecking survey.

  • Speaker
    APC as an entry point to study small molecule regulation of the cell cycle
    Speaker
    Nubia Barbosa Eloy
    Max Planck Institute
    Germany
    Biography

    Nubia Barbosa Eloy has her expertise in Plant Development and Cell Cycle, especially in improving the ways to have better crop and production. During her academic life, she has published several peer reviewed papers about plant growth and development. Her main interest is to study the plant growth to better enhance crop productivity, using cutting edge techniques to achieve her goal.

    Abstract

    The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that plays a major role in the progression of the eukaryotic cell cycle. This unusual protein complex targets key cell-cycle regulators, such as mitotic cyclins and securins, for degradation via the 26S proteasome by ubiquitination, triggering the metaphase-to-anaphase transition and exit from mitosis. The identification of the complete set of genes encoding subunits of the APC in Arabidopsis suggests that the basic processes controlled by proteolysis mediated by ubiquitin in plants are similar to those of other organisms. However, results from several groups indicate that the APC has other specific functions in the regulation of plant development. During the last years, several molecular-biology tools have been extensively used in scientific research for identifying new function of proteins and metabolites. Still, the identification of metabolites, specially which control the cell cycle is not trivial and is characterized by piecemeal progress, especially in plants. In this seminar, we will discuss the methodologies that we are using to identify and characterize metabolites that bind to the APC in the model plant Arabidopsis, and to potentially define their roles in plant development.

  • Speaker
    Mapping the Arabidopsis metabolic landscape by untargeted metabolomics at different environmental conditions
    Speaker
    Si Wu
    Max Planck Institute
    Germany
    Biography

    Si Wu conducted MS-based untargeted metabolomics study to investigate the pathophysiology of complex metabolic disease – hypothyroidism and therapeutic effects of traditional Chinese medicine. She published four metabolomics-related scientific papers as the first author during the Master degree. She worked as an Intern at Agilent Technologies (Shanghai, P.R. China) to conduct Drug Quality Standard Test of Chinese Pharmacopoeia (2010 Edition). At present, she is a PhD candidate waiting for the defense at Max Planck Institute of Molecular Plant Physiology to carry on an integrative research of combining Genome Wide Association Study (GWAS) and network analysis to identify novel genes involved in secondary metabolism in Arabidopsis.

    Abstract

    Metabolic genome-wide association studies (mGWAS), whereupon metabolite levels are regarded as traits, can help unravel the genetic basis of metabolic networks. Aiming to increase the discovery of true metabolite–gene associations, we applied abiotic stress to Arabidopsis thaliana using an integrative approach combining mGWAS and metabolite?transcript correlation-network analysis. 309 natural accessions were grown under two independent environmental conditions (control and stress) and subjected to untargeted LC?MS-based metabolomics; levels of the obtained hydrophilic metabolites were used in GWAS, followed by integration with network-derived metabolite?transcript correlations using a time-course stress experiment. Our two-condition-based GWAS for ~2,000 semi-polar metabolites resulted in the detection of numerous highly resolved mQTL, many of which environment-specific. We show increased discovery of causal genes for well-characterized secondary metabolites by applying GWAS under stress. We, moreover, discovered a large number of hitherto uncharacterized metabolite?gene associations, serving as a rich reservoir for further gene-characterization efforts. Of these, we identified 93 key candidate associations between structural genes and metabolites. We then experimentally validated—using loss-of-function mutants—eight of the novel associations, two of them showing differential genetic regulation in the two environments studied. Our study thus demonstrates the power of combining large-scale untargeted metabolomics-based GWAS with time-course-derived networks, when both approaches are performed under different abiotic environments, to facilitate the identification of metabolite?gene associations. Additionally, it also provides new global insights into the metabolic landscape of Arabidopsis using a strategy that could readily be adapted for other plant species.

Poster
Chair
Speaker
  • null
    Inference of pluripotency control in mouse embryonic stem cells
    Speaker
    Sachiyo Aburatani
    National Institute of Advanced Industrial Science and Technology
    Japan
    Biography

    Sachiyo Aburatani is Deputy Director of new laboratory for Computational Bio Big Data research (CBBD-Open Innovation Lab.) at the National Institute of Advanced Industrial Science and Technology (AIST), Japan. And, she is also a Senior Research Scientist of Biotechnology Research Institute for Drug Discovery at AIST. Her research interests include Systems Biology, Computational Biology, Gene Regulatory Network and Structural Equation Modelling. Her achievements include research in network inferences between genes and other cellular components from expression profiles; inference of environmental chemicals’ effects to human embryonic stem cell; and statistical analysis of the relationships between genes from expression profiles.

    Abstract

    In embryonic stem cells, some transcription factors (TFs) are known to maintain the pluripotent process. To gain insights into the regulatory system to control pluripotency, I inferred regulatory relationships between TFs, which expressed in ES cells. In this study, I applied a method based on structural equation modeling (SEM), combined with factor analysis, to 649 expression profiles of 19 TF genes measured in mouse ES (mES) cells. By the factor analysis, 19 TF genes were regulated by several unmeasured factors. Since the known cell reprograming TF genes (Pou5f1, Sox2, Nanog and Klf4) were regulated by different factors, each estimated factor is considered to be an input signal transduction to control pluripotency in mES cells. In the inferred network model, TF proteins were also arranged as unmeasured factors which control the other TFs. The interpretation of the inferred network model allowed us to reveal the regulatory mechanism for controlling pluripotency in ES cells.

  • null
    Development of quantitative and qualitative analytical method for bile acids in rat bile and evaluation of their changes in aging
    Speaker
    Byung Hwa Jung
    KIST
    South Korea
    Abstract

    Bile acids (BAs) have important roles in physiological functions including the homeostasis of cholesterol, lipid, and as ligands for G protein-coupled receptors (GPCRs). Aging is highly correlated with the incidence of various diseases related to liver and gastrointestinal tract, thus it simply can be guessed that the changes in the level of bile acids are closely related to aging. However, due to the diverse range and a variety of BAs that have different activation potency, a simple, effective and sensitive method is required to screen BAs for accurate quantification and identification. In this study, the quantification method for the 19 targeted BAs in rat bile was developed and validated using ultrahigh-performance liquid chromatography-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS). 22 unknown bile acids were also characterized with their fragmentation patterns at the same time in this method. With the developed method, the change of bile acids level in rat bile according to aging was evaluated. Through statistical analysis, we have found that as the rats get older, unconjugated BAs and glycine-conjugated BAs were decreasing or not changing while taurine-conjugated BAs were increasing in general. Among the unknown BAs, five of the taurine conjugated BAs increased while a glycine conjugated BA decreased that is in corroboration with the trends of the targeted BAs

  • null
    The impact of aging on natural killer cell, cytokines and prostaglandin F2? in non-obese healthy subjects
    Speaker
    Ayoung Lee
    Yonsei University
    South Korea
    Biography

    Ayoung Lee is pursuing her PhD at Yonsei University. She is in Department of Food and Nutrition, Nutrigenetics/Nutrigenomics laboratory, leading by Professor Jong Ho Lee. Her research focuses on Clinical Nutrition; and she is interested in interactions among nutrition, human metabolic profiles, and metabolic diseases. She is currently working with analysis of fatty acid composition in biological samples using GC-MS and GC-TOF-MS.

    Abstract

    Aging, which can be considered as an inevitable process, is often linked to dysregulation of the immune system and oxidative stress. The aim of this study is to investigate the impact of aging on natural killer (NK) cell, cytokines and prostaglandin F2? in non-obese healthy subjects. In this study, 987 healthy participants aged 20-80 years who were not obese were enrolled and grouped as follows: 20-34 (group 1), 35-44 (group 2), 45-54 (group 3), 55-64 (group 4), and 65-80 (group5) years of age. NK cell activity, cytokines in serum and peripheral blood mononuclear cell (PBMC) and urinary 8-epi-prostaglandin F2? (PGF2?) were measured in order to determine age-dependent changes. Interestingly, we found that the levels of serum interferon (IFN)–? in groups 3, 4 and 5 were lower than those in groups 1 and 2. In addition, group 5 was lower than groups 1 and 2 in terms of the levels of serum interleukin (IL)-12. Production of IFN-? by un-stimulated PBMCs was lower in groups 4 and 5 than in groups 1 and 3. On the other hand, serum and PBMC IL-6 in group 5 were higher than those in groups 1, 2, and 3. The level of urinary 8-epi-PGF2? in group 3 was higher than that in group 1. In conclusion, serum IL-12 and both serum and PBMC IFN-? levels were decreased while both serum and PBMC IL-6 and oxidative stress levels were increased in non-obese healthy subjects depending on aging.

  • Probiotic yogurt containing heat-treated Lactobacillus plantarum enhances immune function in the elderly
    Speaker
    Ayoung Lee
    Yonsei University
    South Korea
    Biography

    Ayoung Lee is pursuing her PhD at Yonsei University. She is in Department of Food and Nutrition, Nutrigenetics/Nutrigenomics laboratory, leading by Professor Jong Ho Lee. Her research focuses on Clinical Nutrition; and she is interested in interactions among nutrition, human metabolic profiles, and metabolic diseases. She is currently working with analysis of fatty acid composition in biological samples using GC-MS and GC-TOF-MS.

    Abstract

    The population of elderly people, who often suffer more serious complications of infection than younger people, is rapidly increasing in Korea. The objective of this study was to examine the effect of probiotic yogurt containing heat-treated Lactobacillus plantarum (L. plantarum), a dead form of L. plantarum which was derived from kimchi, on immune function in the elderly. In a randomized, open-label, placebo-controlled study, 200 non-diabetic subjects over 60 years old were divided into two groups to drink 120 ml milk or 120 ml probiotic yogurt containing heat?treated L. plantarum once per day over 12-week period. In this study, natural killer cell activity and serum cytokine and immunoglobulin concentrations were measured for immune function. We found that the levels of natural killer cell activity, interleukin-12 and immunoglobulin G1 were significantly increased in the yogurt group at 12 weeks compared to baseline. Moreover, the yogurt group had significantly greater increase in natural killer cell activity, interferon-? and immunoglobulin G1 than the milk group. In conclusion, consumption of probiotic yogurt containing heat-treated L. plantarum could be beneficial and effective on enhancing immune function in the elderly.

  • The significance of apricot in human health and nutrition
    Speaker
    Zeliha Selamoglu
    Omer Halisdemir University
    Turkey
    Biography

    Zeliha Selamoglu is a Professor in Medical Biology department of Ömer Halisdemir University, Turkey. She completed her PhD in Biology from Inonu University. She has published over 70 peer reviewed journal articles with over 500 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine. She has served as an Editorial Board Member for many Journals.

    Abstract

    Although the apricot [Armeniaca vulgaris L. (Prunus armeniaca L.)] that belongs to the genus Armeniaca of the Rosaceae family is poor in providing the daily energy and protein requirements of the human body, it is a very rich potassium and ?-carotene source. ?-carotene, the precursor of vitamin A, is necessary for the functions of epithelial tissue that surrounds the organs, eye health, bone and tooth development and endocrine glands. Vitamin A also plays an important role in growth and reproduction, and resistance of the body against infections. Another important function of vitamin A is that it could prevent the formation of singlet oxygen, which is responsible from the transformation of normal body cells into cancer cells, or its ability to neutralize singlet oxygen after it is formed. Furthermore, vitamin A enhances the resistance of the organism and the healthy cells, thus protecting the body against cancer. This preventive activity is even more significant with the users of tobacco and alcohol. It was reported that apricot has positive effects on heart failure, kidney diseases, treatment of hepatitis and cirrhosis due to its rich sodium and poor potassium content. One of the most important components of apricot for nutrition and health purposes is dietary fiber. Dietary fiber reduces the risk of diseases such as constipation, appendicitis, hemorrhoids, dental diseases, obesity, diabetes, coronary heart diseases and colon cancer, and ensures the regular intestine functions.

  • Metabolomics of Fhb1-mediated resistance against Fusarium head blight in wheat: An isotope-assisted LC-HRMS approach
    Speaker
    Maria Doppler
    University of Natural Resources and Life Sciences (BOKU)
    Austria
    Biography

    Maria Doppler is a PhD student at University of Natural Resources and Life Sciences, Vienna (BOKU). She is working in a research project which is dealing with metabolomics of Fusarium head blight and the molecular mechanisms underlying plant resistance against this disease. She is focusing on the investigation of secondary plant metabolites by the application of stable isotope labeling and LC-HRMS. She has experience in the field of Metabolomics and received her Master’s degree in Biotechnical Processes at Austrian Biotech University of Applied Sciences after an internship working on the challenging field of identification of plant metabolites with untargeted LC-HRMS.

    Abstract

    Fusarium Head Blight (FHB) is a fungal disease caused by Fusarium graminearum (Fg), producing mycotoxins and negatively affecting yield and quality of small grain cereals such as wheat. Resistance of wheat against FHB is mediated by more than 100 different quantitative trait loci (QTLs), with Fhb1 being located on chromosome 3B and constituting one of the major resistance QTLs. Despite considerable recent research efforts, the molecular mechanism underlying Fhb1 mediated resistance in wheat remains still elusive. According to a recent study, Fhb1 is involved in the regulation of the phenylpropanoid pathway and cell wall reinforcement to prevent fungal spread inside the infected host plant. In the present study, we challenged this hypothesis by the use of 13C labeled phenylalanine (Phe) as metabolic precursor of phenylpropanoids and other phenolic secondary metabolites. To this end, flowering wheat ears of different near isogenic wheat lines, differing in the presence of Fhb1, were treated with Fg, deoxynivalenol or mock (as a control) in a time course experiment. After harvest and sample preparation, LC-HRMS measurement and automated data processing about 1000 plant metabolites including more than 100 Phe-derived metabolites were detected. The presentation will illustrate our isotope-assisted metabolomics approach and will focus on metabolites of the Phe-derived submetabolome and their putative association ; with Fhb1 mediated resistance or susceptibility to FHB in wheat.

    References

    1. Gunnaiah, R., et al., Integrated Metabolo-Proteomic Approach to Decipher the Mechanisms by Which Wheat QTL (Fhb1) Contributes to Resistance against Fusarium graminearum. PLoS ONE, 2012. 7(7): p. e40695.

  • Elucidation of the sequential transcriptional activity in Escherichia coli using time-series RNA-seq data
    Speaker
    Pui Shan Wong
    National Institute of Advanced Industrial Science and Technology
    Japan
    Biography

    Pui Shan Wong completed her Master’s degree in Bioinformatics at University of Auckland, New Zealand. She is now working at National Institute of AIST in Japan under the Biotechnology Research Institute for Drug Discovery and has started her career with six publications.

    Abstract

    Functional genomics and gene regulation inference has readily expanded our knowledge and understanding of gene interactions with regards to expression regulation. With the advancement of transcriptome sequencing in time-series, the ability to study the sequential changes of the transcriptome comes. Here, we present a new method to augment regulation networks accumulated in literature with transcriptome data gathered from time-series experiments to construct a sequential representation of transcription factor activity. We apply our method on a time-series RNA-Seq data set of Escherichia coli as it transitions from growth to stationary phase over five hours and investigate the various activity in gene regulation process by taking advantage of the correlation between regulatory gene pairs to examine their activity on a dynamic network. We analyse the changes in metabolic activity of the pagP gene and associated transcription factors during phase transition, and visualize the sequential transcriptional activity to describe the change in metabolic pathway activity originating from the pagP transcription factor, phoP. We observe a shift from amino acid and nucleic acid metabolism, to energy metabolism during the transition to stationary phase in E. coli.

  • Modeling context-specific metabolic network of mouse pluripotent cell states
    Speaker
    Fatehmeh Khassafi
    Royan Institute for Stem Cell Biology and Technology
    Iran
    Biography

    Fatehmeh Khassafi has received her Bachelor degree in Biology at University of Tehran, which is the most reputable university in Iran. She continued her education in Cell and Developmental Biology at University of Science and Culture in collaboration with Royan Institute – established in 1991 – is one of the pioneers in Stem Cell Research, Cell Therapy and Reproductive Biomedicine in Iran.

    Abstract

    Metabolic network reconstruction which is one of the valuable methods used to predict phenotype and analysis of cell physiology is the mathematical representation that encompasses all metabolic pathways in a cell or an organism. Genome-scale metabolic networks are primarily reconstructed for specific organisms based on their annotated genomes and then, context specific models are needed to facilitate constraint-based analysis in different eukaryotic cell types. Since pluripotent stem cells can be potentially used in regenerative medicine and disease modeling, investigating their functions has recently been at the centre of attention. Pluripotent stem cells are proliferative, so they have different bioenergetics and biosynthetic demands compared to their differentiated counterparts, although the underlying mechanism of this metabolism is still unclear. Furthermore, different pluripotent states display controversies in some metabolic traits also have been shown during induced pluripotent cell generation. Comprehensive assessment of unique metabolism of pluripotent cell is only possible via in-silico modeling of metabolism which also overcomes the limitations of time-consuming and expensive experiments. Here, we reconstructed different types of mouse pluripotent cell specific metabolic models, using transcriptomic data. Further comparison and analysis will be performed on these models leads to description of metabolic features of mouse pluripotent cell states that cast light on underlying mechanisms of cell fate determination. Confirming this, pave the way for functional assays of metabolism of pluripotent cells and elucidate role of metabolism in regulating pluripotent cell conversion and differentiation into various cell types.

  • Saffron as anti-inflammatory agent in human health
    Speaker
    Zeliha Selamoglu
    Omer Halisdemir University
    Turkey
    Biography

    Zeliha Selamoglu is a Professor in Medical Biology department of Ömer Halisdemir University, Turkey. She completed her PhD in Biology from Inonu University. She has published over 70 peer reviewed journal articles with over 500 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine. She has served as an Editorial Board Member for many Journals.

    Abstract

    Saffron (Crocus sativus L.) is an iridaceous plant and grows mainly in Iran, Spain, Kashmir (India and Pakistan), Greece, Azerbaijan, China, Morocco, Mexico, Libya, Turkey and Austria. The main components of saffron are crocin, crocetin, safranal. Crocin is a water-soluble yellow and active component in Crocus sativus L together with safranal. In addition, saffron includes protein, sugar, vitamins, flavonoids, amino acids, vital minerals and other chemical components. Although saffron also includes more than 150 volatile and aromatic compounds such as zeaxanthin, lycopene, ?- and ?-carotene, its golden and orange color is derived from the ?-crocin. Scientific studies on saffron are concentrated in the USA and worldwide. In a new placebo-controlled study conducted in the United States, it was determined that individuals who consumed 176.5 mg of saffron per day, gave up 55% of the unhealthy snacks, lost weight, and this was achieved due to the appetite regulation property of saffron. It was predicted that obesity could be prevented by consumption of saffron. It was also reported to benefit all organs and health problems including bronchitis, asthma, coughing, nervous system, teeth and gums, heart health and eyes. Due to its antioxidant properties as well as hypolipidemic, anti-inflammatory and anti-carcinogenic effects, saffron are also used as a natural agent in traditional medicine for the treatment of diseases.

  • A review on possible acrylamide exposure and its effects during pregnancy
    Speaker
    Zeliha Selamoglu
    Omer Halisdemir University
    Turkey
    Biography

    Zeliha Selamoglu is a Professor in Medical Biology department of Ömer Halisdemir University, Turkey. She completed her PhD in Biology from Inonu University. She has published over 70 peer reviewed journal articles with over 500 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine. She has served as an Editorial Board Member for many Journals.

    Abstract

    The fact that the International Agency for Research on Cancer (IARC, 1994) classified acrylamide as group 2A (a possible carcinogen for humans) has led to an increase in studies on acrylamide worldwide. In a press release issued by the Swedish National Food Administration (SNFA) and the Stockholm University in April 2002, it was reported that acrylamide, which is a chemical substance with a rich carcinogen potential, has formed in high amounts in carbohydrate-rich fried or baked food. Acrylamide, which is widely used in the chemical industry, is known to be neurotoxic, carcinogenic and harmful to the reproductive system in animals. A large amount of acrylamide is formed by frying and baking the food at high temperatures and the individuals consuming this food are exposed to acrylamide in certain amounts every day. Acrylamide may cause damage to rodents during pre- and postnatal development by penetrating the placenta directly. Pregnant women are exposed to food-origin acrylamide during pregnancy and their babies are probably affected as well. Previous studies reported various findings on the mechanism of acrylamide formation, its negative effects on human health, and ways of reducing food-borne acrylamide formation. However, the possible effects of acrylamide on human health are not still fully known. Researchers have recently investigated the damage to the fetus caused by acrylamide biochemical and histologically and in depth, and the results of these research have demonstrated that dose-dependent acrylamide administration leads to severe morphological, biochemical and histological abnormalities in fetal life. To minimize the possible toxic effects of food-borne acrylamide on fetus development due to the fact that it is rather difficult to be protected against food-borne acrylamide toxicity in a world where fast food culture is prevalent, it is recommended that pregnant women should consume plenty of fresh vegetables and fruits daily.

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