Dr Ruan Elliott

Senior Lecturer in Nutrition

Qualifications: BA (Hons) PhD

Email:
Phone: Work: 01483 68 3843
Room no: 21 AY 03

Further information

Biography

Current position: Senior lecturer, Nutritional Sciences Division, Faculty of Health and Medical Sciences, University of Surrey

1994-2009            Senior Scientist, Institute of Food Research Norwich
1992-1994            Post-doctoral Research Fellow, University of British Columbia, Canada
1992                      PhD in Nutritional Metabolism (University of Surrey)
1988                      BA (Hons) Natural Sciences (University of Cambridge)

Research Interests

  • Nutritional modulation of DNA damage:repair
  • Application of functional genomic techniques in nutrition: optimising nutrigenomic study designs, developing concepts for risk-benefit analysis and defining optimal nutrition
  • Defining optimal micronutrient intakes and modelling homeostatic mechanisms (with in particular interest in iron, copper, selenium and zinc)

Research Collaborations

Inter-faculty collaborations:
“Proof of Principle for Resolving Controversies in Mineral Transport” project funded under the Systems and Life Ideas Exchange of the Models programme of the Mathematics in Life and Social Sciences (MILES) project with Drs Matthew Turner and Gianne Derks (Mathematics), Dr Bernadette Moore (Nutritional Sciences) and Dr Theresa Hague (Post Graduate Medical School)

"Mathematical modelling of the repair dynamics of alkylatation damage to DNA in mammalian cells" project funded under the Discipline Hops programme of the Models and Mathematics in Life and Social Sciences (MILES) programme with Dr Philip Aston (Mathematics) and Dr Lisiane Meira (Biochemical Sciences)

National collaborations:
“Impact of non-digestible carbohydrates on biomarkers of GI health: a human intervention study” BBSRC Diet and Health Research Industry Club (DRINC) project (BB/H005021/1) with Professor John Mathers (University of Newcastle) and Professor Ian Johnson (Institute of Food Research, Norwich)

International collaborations:
Network board member and Work Package Leader for the European Nutrigenomics Organisation (NuGO, www.nugo.org), a Network of Excellence funded under the European Commission’s Framework Programme 6.

Publications

Highlights

  • Rubio-Aliaga I, de Roos B, Duthie SJ, Crosley LK, Mayer C, Horgan G, Colquhoun IJ, Le Gall G, Huber F, Kremer W, Rychlik M, Wopereis S, van Ommen B, Schmidt G, Heim C, Bouwman FG, Mariman EC, Mulholland F, Johnson IT, Polley AC, Elliott RM, Daniel H. (2011) 'Metabolomics of prolonged fasting in humans reveals new catabolic markers'. METABOLOMICS, 7 (3), pp. 375-387.
  • Bouwman FG, de Roos B, Rubio-Aliaga I, Crosley LK, Duthie SJ, Mayer C, Horgan G, Polley AC, Heim C, Coort SL. (2011) '2D-electrophoresis and multiplex immunoassay proteomic analysis of different body fluids and cellular components reveal known and novel markers for extended fasting.'. BMC Med Genomics, England: 4

    Abstract

    Proteomic technologies applied for profiling human biofluids and blood cells are considered to reveal new biomarkers of exposure or provide insights into novel mechanisms of adaptation.

  • Heaton SJ, Eady JJ, Parker ML, Gotts KL, Dainty JR, Fairweather-Tait SJ, McArdle HJ, Srai KS, Elliott RM. (2008) 'The use of BeWo cells as an in vitro model for placental iron transport.'. Am J Physiol Cell Physiol, United States: 295 (5), pp. C1445-C1453.

    Abstract

    BeWo cells are a placental cell line that has been widely used as an in vitro model for the placenta. The b30 subclone of these cells can be grown on permeable membranes in bicameral chambers to form confluent cell layers, enabling rates of both nutrient uptake into the cells from the apical surface and efflux from the basolateral membrane to be determined. The aim of this study was to evaluate structural and functional properties of confluent b30 BeWo cell layers grown in bicameral chambers, focusing on the potential application for studying receptor-mediated uptake and transport of transferrin (Tf)-bound iron (Fe-Tf). While it proved extremely difficult to establish and maintain an intact BeWo cell monolayer, it was possible to grow the cells to a confluent multilayer. Iron, applied as Fe-Tf, was rapidly transported across this cell layer; 9.3 +/- 0.5% of the total dose was transported after 8 h, equivalent to 38.8 +/- 2.1 pmol.cm(-2).h(-1). Transfer of Tf across the cell layer was much more limited; 2.4 +/- 0.2% of the total dose was transported after 8 h, equivalent to 5.0 +/- 0.4 pmol.cm(-2).h(-1). Compartmental modeling of these data suggested that iron was transported across the cell layer predominantly, if not exclusively, via a transcellular route, whereas Tf taken up into the cells was predominantly recycled back to the apical compartment. The results suggest that these cells are very efficient at transporting iron and, under carefully controlled conditions, can be a valuable tool for the study of iron transport in the placenta.

  • de Roos B, Duthie SJ, Polley AC, Mulholland F, Bouwman FG, Heim C, Rucklidge GJ, Johnson IT, Mariman EC, Daniel H, Elliott RM. (2008) 'Proteomic methodological recommendations for studies involving human plasma, platelets, and peripheral blood mononuclear cells.'. J Proteome Res, United States: 7 (6), pp. 2280-2290.

    Abstract

    This study was designed to develop, optimize and validate protocols for blood processing prior to proteomic analysis of plasma, platelets and peripheral blood mononuclear cells (PBMC) and to determine analytical variation of a single sample of depleted plasma, platelet and PBMC proteins within and between four laboratories each using their own standard operating protocols for 2D gel electrophoresis. Plasma depleted either using the Beckman Coulter IgY-12 proteome partitioning kit or the Amersham albumin and IgG depletion columns gave good quality gels, but reproducibility appeared better with the single-use immuno-affinity column. The use of the Millipore Filter Device for protein concentration gave a 16% ( p < 0.005) higher recovery of protein in flow-through sample compared with acetone precipitation. The use of OptiPrep gave the lowest level of platelet contamination (1:0.8) during the isolation of PBMC from blood. Several proteins (among which are alpha-tropomyosin, fibrinogen and coagulation factor XIII A) were identified that may be used as biomarkers of platelet contamination in future studies. When identifying preselected spots, at least three out of the four centers found similar identities for 10 out of the 10 plasma proteins, 8 out of the 10 platelet proteins and 8 out of the 10 PBMC proteins. The discrepancy in spot identifications has been described before and may be explained by the mis-selection of spots due to laboratory-to-laboratory variation in gel formats, low scores on the peptide analysis leading to no or only tentative identifications, or incomplete resolution of different proteins in what appears as a single abundant spot. The average within-laboratory coefficient of variation (CV) for each of the matched spots after automatic matching using either PDQuest or ProteomWeaver software ranged between 18 and 69% for depleted plasma proteins, between 21 and 55% for platelet proteins, and between 22 and 38% for PBMC proteins. Subsequent manual matching improved the CV with on average between 1 and 16%. The average between laboratory CV for each of the matched spots after automatic matching ranged between 4 and 54% for depleted plasma proteins, between 5 and 60% for platelet proteins, and between 18 and 70% for PBMC proteins. This variation must be considered when designing sufficiently powered studies that use proteomics tools for biomarker discovery. The use of tricine in the running buffer for the second dimension appears to enhance the

  • Eady JJ, Wortley GM, Wormstone YM, Hughes JC, Astley SB, Foxall RJ, Doleman JF, Elliott RM. (2005) 'Variation in gene expression profiles of peripheral blood mononuclear cells from healthy volunteers'. Physiological Genomics, 22 (3), pp. 402-411.

Journal articles

  • Rubio-Aliaga I, de Roos B, Duthie SJ, Crosley LK, Mayer C, Horgan G, Colquhoun IJ, Le Gall G, Huber F, Kremer W, Rychlik M, Wopereis S, van Ommen B, Schmidt G, Heim C, Bouwman FG, Mariman EC, Mulholland F, Johnson IT, Polley AC, Elliott RM, Daniel H. (2011) 'Metabolomics of prolonged fasting in humans reveals new catabolic markers'. METABOLOMICS, 7 (3), pp. 375-387.
  • Bouwman FG, de Roos B, Rubio-Aliaga I, Crosley LK, Duthie SJ, Mayer C, Horgan G, Polley AC, Heim C, Coort SL. (2011) '2D-electrophoresis and multiplex immunoassay proteomic analysis of different body fluids and cellular components reveal known and novel markers for extended fasting.'. BMC Med Genomics, England: 4

    Abstract

    Proteomic technologies applied for profiling human biofluids and blood cells are considered to reveal new biomarkers of exposure or provide insights into novel mechanisms of adaptation.

  • van Ommen B, El-Sohemy A, Hesketh J, Kaput J, Fenech M, Evelo C, McArdle H, Bouwman J, Lietz G, Mathers J, Fairweather-Tait S, van Kranen H, Elliott R, Wopereis S, Ferguson LR, Meplan C, Perozzi G, Allen L, Revero D, The Micronutrient Genomics Project Working Group . (2010) 'The micronutrient genomics project: creating a community driven knowledge base for micronutrient research'. Genes Nutr, 5 (4), pp. 285-296.
  • van Ommen B, Bouwman J, Dragsted LO, Drevon CA, Elliott R, de Groot P, Kaput J, Mathers JC, Müller M, Pepping F, Saito J, Scalbert A, Radonjic M, Rocca-Serra P, Travis A, Wopereis S, Evelo CT. (2010) 'Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies.'. Genes Nutr, Germany: 5 (3), pp. 189-203.

    Abstract

    The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in 'omics' technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the "Nutritional Phenotype database" (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different-omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed-omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and-omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance)

  • Thompson BAV, Sharp PA, Elliott RM, Fairweather-Tait SJ. (2010) 'The inhibitory effect of calcium on iron absorption may be related to translocation of DMT-1 at the apical membrane of enterocytes'. J Agric Food Chem, 58 (14), pp. 8414-8417.
  • Thompson B, Sharp P, Elliott RM, Al-Mutairi S, Fairweather-Tait SJ. (2010) 'Development of a modified Caco-2 cell model system for studying iron availability in eggs'. J Agric Food Chem, 58 (6), pp. 3833-3839.
  • Doleman JF, Eady JJ, Elliott RM, Foxall RJ, Seers J, Johnson IT, Lund EK. (2010) 'Identification of the Eph receptor pathway as a novel target for eicosapentaenoic acid (EPA) modification of gene expression in human colon adenocarcinoma cells (HT-29).'. Nutr Metab (Lond), England: 7
  • Crosley LK, Duthie SJ, Polley AC, Bouwman FG, Heim C, Mulholland F, Horgan G, Johnson IT, Mariman EC, Elliott RM, Daniel H, de Roos B. (2009) 'Variation in protein levels obtained from human blood cells and biofluids for platelet, peripheral blood mononuclear cell, plasma, urine and saliva proteomics.'. Genes Nutr, Germany: 4 (2), pp. 95-102.

    Abstract

    Blood cells and biofluid proteomics are emerging as a valuable tool to assess effects of interventions on health and disease. This study is aimed to assess the amount and variability of proteins from platelets, peripheral blood mononuclear cells (PBMC), plasma, urine and saliva from ten healthy volunteers for proteomics analysis, and whether protein yield is affected by prolonged fasting. Volunteers provided blood, saliva and morning urine samples once a week for 4 weeks after an overnight fast. Volunteers were fasted for a further 24 h after the fourth sampling before providing their final samples. Each 10 mL whole blood provided 400-1,500 mug protein from platelets, and 100-600 mug from PBMC. 30 muL plasma depleted of albumin and IgG provided 350-650 mug protein. A sample of morning urine provided 0.9-8.6 mg protein/dL, and a sample of saliva provided 70-950 mug protein/mL. None of these yields were influenced by the degree of fasting (overnight or 36 h). In conclusion, in contrast to the yields from plasma, platelets and PBMC, the protein yields of urine and saliva samples were highly variable within and between subjects. Certain disease conditions may cause higher or lower PBMC counts and thus protein yields, or increased urinary protein levels.

  • Baccini M, Bachmaier EM, Biggeri A, Boekschoten MV, Bouwman FG, Brennan L, Caesar R, Cinti S, Coort SL, Crosley K, Daniel H, Drevon CA, Duthie S, Eijssen L, Elliott RM, van Erk M, Evelo C, Gibney M, Heim C, Horgan GW, Johnson IT, Kelder T, Kleemann R, Kooistra T, van Iersel MP, Mariman EC, Mayer C, McLoughlin G, Müller M, Mulholland F, van Ommen B, Polley AC, Pujos-Guillot E, Rubio-Aliaga I, Roche HM, de Roos B, Sailer M, Tonini G, Williams LM, de Wit N, For the NuGO PPS Team . (2008) 'The NuGO proof of principle study package: a collaborative research effort of the European Nutrigenomics Organisation.'. Genes Nutr, 3 (3-4), pp. 147-151.
  • Heaton SJ, Eady JJ, Parker ML, Gotts KL, Dainty JR, Fairweather-Tait SJ, McArdle HJ, Srai KS, Elliott RM. (2008) 'The use of BeWo cells as an in vitro model for placental iron transport.'. Am J Physiol Cell Physiol, United States: 295 (5), pp. C1445-C1453.

    Abstract

    BeWo cells are a placental cell line that has been widely used as an in vitro model for the placenta. The b30 subclone of these cells can be grown on permeable membranes in bicameral chambers to form confluent cell layers, enabling rates of both nutrient uptake into the cells from the apical surface and efflux from the basolateral membrane to be determined. The aim of this study was to evaluate structural and functional properties of confluent b30 BeWo cell layers grown in bicameral chambers, focusing on the potential application for studying receptor-mediated uptake and transport of transferrin (Tf)-bound iron (Fe-Tf). While it proved extremely difficult to establish and maintain an intact BeWo cell monolayer, it was possible to grow the cells to a confluent multilayer. Iron, applied as Fe-Tf, was rapidly transported across this cell layer; 9.3 +/- 0.5% of the total dose was transported after 8 h, equivalent to 38.8 +/- 2.1 pmol.cm(-2).h(-1). Transfer of Tf across the cell layer was much more limited; 2.4 +/- 0.2% of the total dose was transported after 8 h, equivalent to 5.0 +/- 0.4 pmol.cm(-2).h(-1). Compartmental modeling of these data suggested that iron was transported across the cell layer predominantly, if not exclusively, via a transcellular route, whereas Tf taken up into the cells was predominantly recycled back to the apical compartment. The results suggest that these cells are very efficient at transporting iron and, under carefully controlled conditions, can be a valuable tool for the study of iron transport in the placenta.

  • Hurst R, Elliott RM, Goldson AJ, Fairweather-Tait SJ. (2008) 'Se-methylselenocysteine alters collagen gene and protein expression in human prostate cells.'. Cancer Lett, Ireland: 269 (1), pp. 117-126.

    Abstract

    The anti-cancer activity of selenium is dose-dependent and species-specific but the mechanism is unclear. Se-methylselenocysteine (MSC), found in selenium-enriched alliums, is one of the most potent forms. We exposed two human prostate cell lines (LNCaP clone FGC and PNT1A) to nutritionally relevant doses of MSC and selenite, ranging from deficient to the equivalent of selenium supplementation in humans. The cells were adapted for one month to attain steady-state selenium status. Two microarray platforms, an in-house printed microarray (14,000 genes) and the Affymetrix U133A array (22,000 genes) were used to probe the molecular effects of selenium dose and form and several selenium-responsive genes were identified, many of which have been ascribed to cancer cell growth and progression. In response to MSC supplementation, the expression of 23 genes changed significantly, including several collagen genes. Quantitative RT-PCR assays were designed and optimized for four of the collagen genes to validate array data. Significant decreases in expression of collagen type I alpha 1 (COL1A1), COL1A2 and COL7A1 genes were observed in cells adapted to MSC supplementation compared to the control and selenite exposed cells. There were significant increases in genes encoding other types of collagen, including significant increases in COL6A1 and COL4A5 in response to MSC dose. Functional changes in collagen type I protein expression in response to MSC were confirmed by ELISA. This study reveals for the first time that MSC can alter the expression of several types of collagen and thus potentially modulate the extracellular matrix and stroma, which may at least partially explain the anti-cancer activity of MSC.

  • van Ommen B, Keijer J, Kleemann R, Elliott R, Drevon CA, McArdle H, Gibney M, Müller M. (2008) 'The challenges for molecular nutrition research 2: quantification of the nutritional phenotype.'. Genes Nutr, Germany: 3 (2), pp. 51-59.

    Abstract

    In quantifying the beneficial effect of dietary interventions in healthy subjects, nutrition research meets a number of new challenges. Inter individual variation in biomarker values often is larger than the effect related to the intervention. Healthy subjects have a remarkable capacity to maintain homeostasis, both through direct metabolic regulation, metabolic compensation of altered diets, and effective defence and repair mechanisms in oxidative and inflammatory stress. Processes involved in these regulatory activities essentially different from processes involved in early onset of diet related diseases. So, new concepts and approaches are needed to better quantify the subtle effects possibly achieved by dietary interventions in healthy subjects. Apart from quantification of the genotype and food intake (these are discussed in separate reviews in this series), four major areas of innovation are discussed: the biomarker profile concept, perturbation of homeostasis combined with omics analysis, imaging, modelling and fluxes. All of these areas contribute to a better understanding and quantification of the nutritional phenotype.

  • Elliott RM. (2008) 'Transcriptomics and micronutrient research.'. Br J Nutr, England: 99 Suppl 3, pp. S59-S65.

    Abstract

    This review examines the extent to which transcriptomic methods have lived up to their promise in the context of nutrition research, placing particular emphasis on examples from micronutrient research. A case is made that the high quality platform technologies now available, together with established standards and systems for data storage and exchange and powerful new methods of data analysis, mean that microarrays have reached a level of technical maturity at which they can be exploited to their full potential. In the context of nutrition and micronutrient research, transcriptomic methods have already been widely applied, albeit primarily in studies using cell lines and animal models. Using this type of approach, a multitude of genes regulated at the mRNA level by dietary components has been identified and this, in turn, has provided new insights into the biological processes affected by nutritional parameters. Evidence from the very limited number of published transcriptomics-based nutritional studies performed in human volunteers suggests that, with appropriate study design, it is feasible to apply transcriptomic methods successfully in dietary intervention trials. On the other hand, gene expression-based biomarker development still poses a major challenge. Here the use of expression profile 'signatures', rather than single genes, may provide a solution. Approaches designed to identify such 'signatures' are being developed and tested widely, primarily in the context of medical research. The applicability and power of such approaches should also be evaluated in the context of nutrition.

  • de Roos B, Duthie SJ, Polley AC, Mulholland F, Bouwman FG, Heim C, Rucklidge GJ, Johnson IT, Mariman EC, Daniel H, Elliott RM. (2008) 'Proteomic methodological recommendations for studies involving human plasma, platelets, and peripheral blood mononuclear cells.'. J Proteome Res, United States: 7 (6), pp. 2280-2290.

    Abstract

    This study was designed to develop, optimize and validate protocols for blood processing prior to proteomic analysis of plasma, platelets and peripheral blood mononuclear cells (PBMC) and to determine analytical variation of a single sample of depleted plasma, platelet and PBMC proteins within and between four laboratories each using their own standard operating protocols for 2D gel electrophoresis. Plasma depleted either using the Beckman Coulter IgY-12 proteome partitioning kit or the Amersham albumin and IgG depletion columns gave good quality gels, but reproducibility appeared better with the single-use immuno-affinity column. The use of the Millipore Filter Device for protein concentration gave a 16% ( p < 0.005) higher recovery of protein in flow-through sample compared with acetone precipitation. The use of OptiPrep gave the lowest level of platelet contamination (1:0.8) during the isolation of PBMC from blood. Several proteins (among which are alpha-tropomyosin, fibrinogen and coagulation factor XIII A) were identified that may be used as biomarkers of platelet contamination in future studies. When identifying preselected spots, at least three out of the four centers found similar identities for 10 out of the 10 plasma proteins, 8 out of the 10 platelet proteins and 8 out of the 10 PBMC proteins. The discrepancy in spot identifications has been described before and may be explained by the mis-selection of spots due to laboratory-to-laboratory variation in gel formats, low scores on the peptide analysis leading to no or only tentative identifications, or incomplete resolution of different proteins in what appears as a single abundant spot. The average within-laboratory coefficient of variation (CV) for each of the matched spots after automatic matching using either PDQuest or ProteomWeaver software ranged between 18 and 69% for depleted plasma proteins, between 21 and 55% for platelet proteins, and between 22 and 38% for PBMC proteins. Subsequent manual matching improved the CV with on average between 1 and 16%. The average between laboratory CV for each of the matched spots after automatic matching ranged between 4 and 54% for depleted plasma proteins, between 5 and 60% for platelet proteins, and between 18 and 70% for PBMC proteins. This variation must be considered when designing sufficiently powered studies that use proteomics tools for biomarker discovery. The use of tricine in the running buffer for the second dimension appears to enhance the

  • Elliott R, Pico C, Dommels Y, Wybranska I, Hesketh J, Keijer J. (2007) 'Nutrigenomic approaches for benefit-risk analysis of foods and food components: defining markers of health.'. Br J Nutr, England: 98 (6), pp. 1095-1100.

    Abstract

    To be able to perform a comprehensive and rigorous benefit-risk analysis of individual food components, and of foods, a number of fundamental questions need to be addressed first. These include whether it is feasible to detect all relevant biological effects of foods and individual food components, how such effects can confidently be categorised into benefits and risks in relation to health and, for that matter, how health can be quantified. This article examines the last of these issues, focusing upon concepts for the development of new biomarkers of health. Clearly, there is scope for refinement of classical biomarkers so that they may be used to detect even earlier signs of disease, but this approach defines health solely as the absence of detectable disease or disease risk. We suggest that the health of a biological system may better be reflected by its ability to withstand and manage relevant physiological challenges so that homeostasis is maintained. We discuss the potential for expanding the range of current challenge tests for use in conjunction with functional genomic technologies to develop new types of biomarkers of health.

  • Astley SB, Elliott RM. (2007) 'The European Nutrigenomics Organisation: linking genomics, nutrition and health research'. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, 87 (7), pp. 1180-1184.
  • Elliott RM, Johnson IT. (2007) 'Nutrigenomic approaches for obesity research.'. Obes Rev, England: 8 Suppl 1, pp. 77-81.
  • Heaton SJ, Eady JJ, Fairweather-Tait SJ, MCardle HJ, Srai KS, Elliott RM. (2007) 'BeWo cells as an in vitro model for iron transport across the placenta'. PROCEEDINGS OF THE NUTRITION SOCIETY, 66, pp. 17A-17A.
  • Dawes LJ, Elliott RM, Reddan JR, Wormstone YM, Wormstone IM. (2007) 'Oligonucleotide microarray analysis of human lens epithelial cells: TGFbeta regulated gene expression.'. Mol Vis, United States: 13, pp. 1181-1197.

    Abstract

    Transforming growth factor beta (TGFbeta), a pro-fibrotic cytokine has been proposed a causative factor in the progression of lens pathologies including posterior capsule opacification (PCO), a condition that occurs after cataract surgery. This study employs oligonucleotide microarrays to provide a global profile of gene expression in FHL 124 cells, to identify changes in gene expression following treatment with TGFbeta1 and TGFbeta2, and to enable putative genes relating to TGFbeta regulation and PCO to be identified.

  • Rocca-Serra P, Elliott RM. (2006) 'Data storage: bringing us a step closer to data sharing?'. Br J Nutr, England: 95 (6), pp. 1237-1239.
  • Hesketh J, Wybranska I, Dommels Y, King M, Elliott R, Pico C, Keijer J. (2006) 'Nutrient-gene interactions in benefit-risk analysis.'. Br J Nutr, England: 95 (6), pp. 1232-1236.

    Abstract

    Individuals respond differently to nutrients and foods. This is reflected in different levels of benefits and risks at the same intake of a nutrient and, consequently, different 'windows of benefit' in terms of nutrient intake. This has led recently to the concept of 'personalised nutrition'. Genetic factors such as single nucleotide polymorphisms may be one source of this inter-individual variation in benefit-risk response to nutrients. In 2004 a European Union-funded network of excellence in the area of nutrigenomics (European Nutrigenomics Organisation; NuGO) organised a workshop on the role of nutrient-gene interactions in determining benefit-risk of nutrients and diet. The major issues discussed at the workshop are presented in the present paper and highlighted with examples from the presentations. The overall consensus was that although genetics provides a new vision where genetic information could in the future be used to provide knowledge on disease predisposition and nutritional requirements, such a goal is still far off and much more research is required before we can reliably include genetic factors in the risk-benefit assessment of nutrients and diets.

  • Wortley GM, Elliott RM, Harvey LJ, Fairweath-Tait SJ. (2006) 'Copper homeostasis: use of in vitro cell systems and transcriptional analysis to detect markers of copper regulation in human subjects.'. PROCEEDINGS OF THE NUTRITION SOCIETY, 65, pp. 103A-103A.
  • Kaput J, Ordovas JM, Ferguson L, van Ommen B, Rodriguez RL, Allen L, Ames BN, Dawson K, German B, Krauss R, Malyj W, Archer MC, Barnes S, Bartholomew A, Birk R, van Bladeren P, Bradford KJ, Brown KH, Caetano R, Castle D, Chadwick R, Clarke S, Clément K, Cooney CA, Corella D, Manica da Cruz IB, Daniel H, Duster T, Ebbesson SO, Elliott R, Fairweather-Tait S, Felton J, Fenech M, Finley JW, Fogg-Johnson N, Gill-Garrison R, Gibney MJ, Gillies PJ, Gustafsson JA, Hartman JL, He L, Hwang JK, Jais JP, Jang Y, Joost H, Junien C, Kanter M, Kibbe WA, Koletzko B, Korf BR, Kornman K, Krempin DW, Langin D, Lauren DR, Ho Lee J, Leveille GA, Lin SJ, Mathers J, Mayne M, McNabb W, Milner JA, Morgan P, Muller M, Nikolsky Y, van der Ouderaa F, Park T, Pensel N, Perez-Jimenez F, Poutanen K, Roberts M, Saris WH, Schuster G, Shelling AN, Simopoulos AP, Southon S, Tai ES, Towne B, Trayhurn P, Uauy R, Visek WJ, Warden C, Weiss R, Wiencke J, Winkler J, Wolff GL, Zhao-Wilson X, Zucker JD. (2005) 'The case for strategic international alliances to harness nutritional genomics for public and personal health.'. Br J Nutr, England: 94 (5), pp. 623-632.

    Abstract

    Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

  • Eady JJ, Wortley GM, Wormstone YM, Hughes JC, Astley SB, Foxall RJ, Doleman JF, Elliott RM. (2005) 'Variation in gene expression profiles of peripheral blood mononuclear cells from healthy volunteers'. Physiological Genomics, 22 (3), pp. 402-411.
  • Astley SB, Elliott RM. (2005) 'How strong is the evidence that lycopene supplementation can modify biomarkers of oxidative damage and DNA repair in human lymphocytes?'. J Nutr, United States: 135 (8), pp. 2071S-2073S.
  • Elliott R. (2005) 'Mechanisms of genomic and non-genomic actions of carotenoids.'. Biochim Biophys Acta, Netherlands: 1740 (2), pp. 147-154.

    Abstract

    Carotenoids are highly bioactive dietary compounds that have the potential to have significant effects on human health. It is becoming increasingly clear that the various biological effects that carotenoids exert could be driven via a number of different mechanisms. These include direct pro- and antioxidant effects, redox sensitive cell signalling, vitamin A signalling pathways and other as yet unidentified mechanisms. This article provides an overview of the known effects of carotenoids and discusses the use of model systems and functional genomic approaches further to elucidate their modes of action.

  • Garosi P, De Filippo C, van Erk M, Rocca-Serra P, Sansone SA, Elliott R. (2005) 'Defining best practice for microarray analyses in nutrigenomic studies.'. Br J Nutr, England: 93 (4), pp. 425-432.

    Abstract

    Microarrays represent a powerful tool for studies of diet-gene interactions. Their use is, however, associated with a number of technical challenges and potential pitfalls. The cost of microarrays continues to drop but is still comparatively high. This, coupled with the complex logistical issues associated with performing nutritional microarray studies, often means that compromises have to be made in the number and type of samples analysed. Additionally, technical variations between array platforms and analytical procedures will almost inevitably lead to differences in the transcriptional responses observed. Consequently, conflicting data may be produced, important effects may be missed and/or false leads generated (e.g. apparent patterns of differential gene regulation that ultimately prove to be incorrect or not significant). This is likely to be particularly true in the field of nutrition, in which we expect that many dietary bioactive agents at nutritionally relevant concentrations will elicit subtle changes in gene transcription that may be critically important in biological terms but will be difficult to detect reliably. Thus, great care should always be taken in designing and executing microarray studies. This article seeks to provide an overview of both the main practical and theoretical considerations in microarray use that represent potential sources of technical variation and error. Wherever possible, recommendations are made on what we propose to be the best approach. The overall aims are to provide a basic framework of advice for researchers who are new to the use of microarrays and to promote a discussion of standardisation and best practice in the field.

  • Elliott RM. (2005) 'Genes, genomes and molecular biology in nutrition research: A story of opportunities and challenges'. Current Topics in Nutraceutical Research, 3 (3), pp. 189-192.

    Abstract

    The wealth of freely available genetic information derived from genome mapping projects and the development of functional genomic and other powerful molecular biological tools have lead to profound changes in the scope of life science research and the way it is performed. As in many other disciplines, scientists in the fields of food science and nutrition are now beginning to fully realise the enormous potential these new resources and are seeking to integrate them into their research. However, there are still a number of issues specific to nutrition research that need to be addressed to ensure that this opportunity is exploited to the full. Copyright © 2005 by New Century Health Publishers, LLC.

  • Astley SB, Elliott RM. (2005) 'The European Nutrigenomics Organisation: linking genomics, nutrition and health research (NuGO)'. TRENDS IN FOOD SCIENCE & TECHNOLOGY, 16 (4), pp. 155-161.
  • Astley SB, Hughes DA, Wright AJ, Elliott RM, Southon S. (2004) 'DNA damage and susceptibility to oxidative damage in lymphocytes: effects of carotenoids in vitro and in vivo.'. Br J Nutr, England: 91 (1), pp. 53-61.

    Abstract

    Reports on the effects of carotenoids are conflicting. The present paper examines similarities and differences from contiguous studies in vitro and in vivo. Single-cell gel electrophoresis was used to measure the frequency of single-strand breaks (SSB) in the cell line MOLT-17 (as a model system) and human peripheral blood lymphocytes (PBL). MOLT-17 cells were supplemented with beta-carotene, lutein or lycopene at a range of concentrations (0.00-8.00 micromol/l) using a liposome delivery method. Uptake was dose-dependent. beta-Carotene concentration in the media had no effect on SSB in control cells, but incubation with lycopene or lutein (>2.00 micromol/l) increased the numbers of SSB in control cells. MOLT-17 DNA was less susceptible to oxidative damage (100 micromol H2O2/l, 5 min, 4 degrees C) following incubation with carotenoids between 0.50 and 1.00 micromol/l; at >1.00 micromol/l the effects were ambiguous. Apparently healthy male volunteers supplemented their habitual diets with lutein, beta-carotene or lycopene (natural isolate capsules, 15 mg/d, 4 weeks) in three independent studies, raising plasma concentrations to different extents. Lycopene and lutein had no effect on SSB in control PBL or following oxidative challenge. However, increased plasma beta-carotene was associated with more SSB in control cells whilst PBL DNA resistance to oxidative damage ex vivo was unaffected. These results suggest that the carotenoids are capable of exerting two overlapping but distinct effects: antioxidant protection by scavenging DNA-damaging free radicals and modulation of DNA repair mechanisms.

  • Astley SB, Elliott RM. (2004) 'The European Nutrigenomics Organisation - Linking genomics, nutrition and health research'. Nutrition Bulletin, 29 (3), pp. 254-261.

    Abstract

    We are exposed to a complex mixture of food compounds in the womb and eat a composite mixture of foods throughout life. Our taste changes as we grow and mature, and we become influenced by external factors such as holidays and advertising by the food industry. Intricate biochemical processes extract energy and other useful components, enabling us to grow and live and keep our bodies and minds functioning effectively. There are, however, many food compounds that have biological effects within our bodies, and diet and disease are intimately associated. To address the fractured nature of nutrigenomic research, leading centres in nutritional research from across Europe have put together a Network of Excellence, the European Nutrigenomics Organisation (NuGO): linking genomics, nutrition and health research. Led by Dr Ben van Ommen of the Dutch Centre for Human Nutrigenomics, NuGO has been awarded €17.3 million over a period of 6 years. The project has been over a year, in preparation and currently has 22 partners from 10 EU member states. © 2004 British Nutrition Foundation.

  • Astley SB, Elliott RM, Archer DB, Southon S. (2004) 'Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage: repair balance in human lymphocytes.'. Br J Nutr, England: 91 (1), pp. 63-72.

    Abstract

    Epidemiological evidence has shown that the habitual consumption of diets high in fruits and vegetables is associated with reduced risk of cancers. The challenge is to identify causal mechanisms of effect. The aim of the current study was to determine whether an increase in rate of removal of DNA single-strand breaks (SSB) following oxidative challenge could be provoked ex vivo in peripheral blood lymphocytes (PBL). The PBL were isolated from apparently healthy volunteers following dietary intervention with: (1) a mixed carotene capsule; (2) a daily portion of cooked minced carrots; (3) a matched placebo; (4) a portion of mandarin oranges; (5) vitamin C tablets. Single-cell gel electrophoresis was employed to measure baseline levels of SSB and DNA susceptibility to oxidative damage, and to monitor the number of SSB over 4 h, in both unchallenged and H2O2-treated PBL. The enzymatic capacity for repair of different types of DNA oxidative lesions was also measured using two related cell-free assays. There was no evidence that any of the dietary supplementation regimens altered baseline levels of SSB, provided any direct antioxidant protection or altered DNA repair capacity, with two exceptions: the number of SSB following exposure to H2O2 decreased more rapidly in PBL from volunteers given the mixed carotene capsules and repair patch synthesis activity in PBL increased from volunteers given the cooked carrots. These results suggest that carotenoids and carotenoid-rich foods can influence DNA damage:repair by modulation of discrete stages in the DNA repair mechanisms.

  • Elliott R, Ong TJ. (2002) 'Science, medicine, and the future - Nutritional genomics'. BRITISH MEDICAL JOURNAL, 324 (7351), pp. 1438-1442.
  • Jackson MJ, Papa S, Bolaños J, Bruckdorfer R, Carlsen H, Elliott RM, Flier J, Griffiths HR, Heales S, Holst B, Lorusso M, Lund E, Øivind Moskaug J, Moser U, Di Paola M, Polidori MC, Signorile A, Stahl W, Viña-Ribes J, Astley SB. (2002) 'Antioxidants, reactive oxygen and nitrogen species, gene induction and mitochondrial function.'. Mol Aspects Med, England: 23 (1-3), pp. 209-285.
  • Astley SB, Elliott RM, Archer DB, Southon S. (2002) 'Increased cellular carotenoid levels reduce the persistence of DNA single-strand breaks after oxidative challenge.'. Nutr Cancer, United States: 43 (2), pp. 202-213.

    Abstract

    Dietary antioxidants, such as the carotenoids, may protect DNA from oxidative damage. This has been proposed to explain the epidemiological association between higher consumption of fruits and vegetables, which are rich in antioxidants, and lower incidence of cancer. However, this remains to be demonstrated conclusively. The effects of carotenoid supplementation on 1) baseline DNA damage, 2) susceptibility of cellular DNA to oxidative attack, and 3) DNA repair were measured in the human lymphocyte cell line Molt-17. Baseline DNA damage, susceptibility to oxidant attack (100 mumol/l H2O2 for 5 min at 4 degrees C), and disappearance of DNA single-strand breaks (SSB) after oxidative challenge were monitored by single-cell gel electrophoresis. DNA repair patch synthesis activity in cell extracts was determined using assays that measure nucleotide incorporation during repair of oxidative lesions in template DNA. Unlike single-cell gel electrophoresis, the parameters measured with these assays are not dependent on strand break religation. There was no evidence that beta-carotene, lutein, or beta-cryptoxanthin supplementation protected cellular DNA from oxidation under basal conditions or after oxidative challenge. However, only carotenoid-supplemented cells exhibited a significant decrease in numbers of SSB over a 2-h period after treatment with H2O2. Carotenoid supplementation did not provoke any detectable change in repair patch synthesis activity. We conclude that supplementation with carotenoids at 8 mumol/l does not provide significant antioxidant protection for DNA in Molt-17 lymphocytes but may enhance recovery of cells from oxidative challenge, as measured by loss of SSB. We argue that these data are most consistent with carotenoids acting to enhance DNA strand break repair.

  • Elliott RM, Astley SB, Southon S, Archer DB. (2000) 'Measurement of cellular repair activities for oxidative DNA damage.'. Free Radic Biol Med, UNITED STATES: 28 (9), pp. 1438-1446.

    Abstract

    Two related assays capable of determining cell extract repair activities for different oxidative lesions in DNA are described. Both assays measure the incorporation of radiolabeled nucleotides during repair of an oxidatively damaged template in a cell-free system. The assays differ in the type of oxidative damage present in the DNA. In one, singlet oxygen is used to generate predominantly 8-oxo-2'-deoxyguanosine lesions. In the other, hydroxyl radicals are used to generate a broad spectrum of damage including oxidized bases and strand breaks. Assay conditions were adjusted to ensure that radiolabel incorporation was directly proportional to cell extract repair activity. These assays represent sensitive tools for investigating the regulation of repair systems for oxidative DNA damage.

  • Watson AJ, Worley J, Elliott RM, Jeenes DJ, Archer DB. (2000) 'Cloning stress-induced genes from Aspergillus niger using polymerase chain reaction-augmented subtractive hybridization'. Analytical Biochemistry, 277 (1), pp. 162-165.
  • Elliott RM, Southon S, Archer DB. (1999) 'Oxidative insult specifically decreases levels of a mitochondrial transcript'. Free Radical Biology and Medicine, 26 (5-6), pp. 646-655.
  • Schieldrop PJ, Gelling RW, Elliott RM, Hewitt J, Kieffer TJ, McIntosh CH, Pederson RA. (1996) 'Isolation of a murine glucose-dependent insulinotropic polypeptide (GIP) cDNA from a tumor cell line (STC6-14) and quantification of glucose-induced increases in GIP mRNA'. Biochimica et Biophysica Acta -Gene Structure and Expression, 1308 (2), pp. 111-113.
  • Jia X, Elliott R, Kwok YN, Pederson RA, McIntosh CH. (1995) 'Altered glucose dependence of glucagon-like peptide I(7-36)-induced insulin secretion from the Zucker (fa/fa) rat pancreas.'. Diabetes, UNITED STATES: 44 (5), pp. 495-500.

    Abstract

    In previous studies on the enteroinsular axis in Zucker rats, it was found that glucose-dependent insulinotropic polypeptide (GIP) levels were normal in obese animals, but the glucose threshold for the insulinotropic action of GIP in the perfused rat pancreas was reduced. Glucagon-like peptide I (GLP-I)(7-36) is also an important incretin, and in the current study, glucose, insulin, and immunoreactive (IR)-COOH-terminal GLP-I responses to oral glucose were compared in lean (Fa/?) and obese (fa/fa) rats. In addition, the concentration thresholds for stimulation and glucose dependence of perfused pancreases to GLP-I(7-36) were examined. Glucose responses to oral glucose were similar in fa/fa and Fa/? rats. Obese animals were hyperinsulinemic when fasting and after oral glucose. Significant increases in IR-GLP-I levels in response to glucose were only observed in fa/fa rats. Perfused pancreases from fa/fa rats hypersecreted insulin at all glucose concentrations. In the presence of 4.4 mmol/l glucose, GLP-I(7-36) increased insulin secretion in fa/fa pancreases approximately 25-fold, whereas there was only a 5-fold increase in Fa/? pancreases. Pancreases from fa/fa rats, perfused with a glucose gradient (2.8-11 mmol/l) in the presence of GLP-I(7-36), responded with an immediate increase in insulin secretion, i.e., at a glucose concentration of 2.8 mmol/l, whereas Fa/? pancreases required a minimum of 4.22 mmol/l glucose for stimulation. With high glucose (16.7 mmol/l), both fa/fa and Fa/? rat pancreases exhibited similar responsiveness to GLP-I(7-36), having thresholds of < 50 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Elliott RM, Morgan LM, Tredger J, Wright J. (1994) 'The effects of cereal source and processing on the metabolic responses to commercially available breakfast cereals and breads'. International Journal of Food Sciences and Nutrition, 45 (3), pp. 217-222.
  • Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V. (1993) 'Glucagon-like peptide-1 (7-36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns.'. J Endocrinol, ENGLAND: 138 (1), pp. 159-166.

    Abstract

    The acute effects of different macronutrients on the secretion of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) and glucose-dependent insulinotropic polypeptide (GIP) were compared in healthy human subjects. Circulating levels of the two hormones were measured over a 24-h period during which subjects consumed a mixed diet. In the first study, eight subjects consumed three equicaloric (375 kcal) test meals of carbohydrate, fat and protein. Small increases in plasma GLP-1(7-36) amide were found after all meals. Levels reached a maximum 30 min after the carbohydrate and 150 min after the fat load. Ingestion of both carbohydrate and fat induced substantial rises in GIP secretion, but the protein meal had no effect. In a second study, eight subjects consumed 75 g glucose or the equivalent portion of complex carbohydrate as boiled brown rice or barley. Plasma GIP, insulin and glucose levels increased after all three meals, the largest increase being observed following glucose and the smallest following the barley meal. Plasma GLP-1(7-36)amide levels rose only following the glucose meal. In the 24-h study, plasma GLP-1(7-36)amide and GIP concentrations were increased following every meal and remained elevated throughout the day, only falling to fasting levels at night. The increases in circulating GLP-1(7-36)amide and GIP levels following carbohydrate or a mixed meal are consistent with their role as incretins. The more sustained rises observed in the daytime during the 24-h study are consistent with an anabolic role in lipid metabolism.

  • MORGAN L, TREDGER J, WILKINSON J, ELLIOTT R, HOWLAND R, MARKS V. (1992) 'POSTPRANDIAL GIP RESPONSES TO A MIXED MEAL IN LEAN AND OBESE SUBJECTS'. REGULATORY PEPTIDES, 40 (2), pp. 213-213.
  • ELLIOTT R, MORGAN L, TREDGER J, CHARLES S, WRIGHT J, MARKS V. (1992) 'ACUTE AND 24-HOUR GLP-1 AND GIP RESPONSES TO INDIVIDUAL MACRONUTRIENTS AND WHOLE FOOD IN MAN'. REGULATORY PEPTIDES, 40 (2), pp. 141-141.

Conference papers

  • Jackson MJ, Elliott RM, Lund E, Papa S, Astley SB. (2002) 'Antioxidants, reactive oxygen and nitrogen species, gene induction and mitochondrial function.'. TAYLOR & FRANCIS LTD FREE RADICAL RESEARCH, CHURCHILL COLL, CAMBRIDGE, ENGLAND: Conference on European Research on Functional Effects of Dietary Antioxidants - Benefits and Risks 36, pp. 14-14.
  • Astley S, Elliott R, Archer D, Southon S, Johnson IT, Fenwick GR. (2000) 'DNA damage and repair: Relative responses to antioxidant nutrients in the diet'. ROYAL SOC CHEMISTRY DIETARY ANTICARCINOGENS AND ANTIMUTAGENS, UNIV E ANGLIA, NORWICH, ENGLAND: 3rd Conference on Food and Cancer Prevention (255), pp. 138-142.
  • Elliott R, Astley S, Southon S, Archer D, Johnson IT, Fenwick GR. (2000) 'The development of DNA repair assays which show that dietary carrots stimulate DNA repair activity'. ROYAL SOC CHEMISTRY DIETARY ANTICARCINOGENS AND ANTIMUTAGENS, UNIV E ANGLIA, NORWICH, ENGLAND: 3rd Conference on Food and Cancer Prevention (255), pp. 125-128.
  • MORGAN L, ELLIOTT R, TREDGER J, NIGHTINGALE J, MARKS V. (1993) 'GLP-1 SECRETION IN RESPONSE TO NUTRIENTS IN MAN'. KARGER DIGESTION, COPENHAGEN, DENMARK: International Symposium on Glucagon-Like Peptide-1 54 (6), pp. 374-376.
  • OBEN J, ELLIOTT R, MORGAN L, FLETCHER J, MARKS V, AILHAUD G, GUYGRAND B, LAFONTAN M, RICQUIER D. (1992) 'THE ROLE OF GUT HORMONES IN THE ADIPOSE-TISSUE METABOLISM OF LEAN AND GENETICALLY-OBESE (OB OB) MICE'. JOHN LIBBEY & CO OBESITY IN EUROPE 91, NICE, FRANCE: 3RD EUROPEAN CONGRESS ON OBESITY, pp. 269-272.
  • MARKS V, MORGAN L, OBEN J, ELLIOTT R. (1991) 'GUT HORMONES IN GLUCOSE-HOMEOSTASIS'. C A B INTERNATIONAL PROCEEDINGS OF THE NUTRITION SOCIETY, ROYAL SOC MED, LONDON, ENGLAND: SYMP AT THE SCIENTIFIC MEETING OF THE NUTRITION SOC : MEDITERRANEAN FOOD AND HEALTH 50 (3), pp. 545-552.

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