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FellowshipsThe Stephan Weiland Fellowships have now been awarded and undertaken. These were completed by Maria Vasilieva, from SSMU, Giovanni Malerba from the University of Verona, Bertrand Sudre from Univeristy of Franche Comte, Besancon and Markus Ege from University of Munich and Paul Cardenas, who was partially funded from Ga2len, in addition to GABRIEL funding, has completed his Fellowship at Imperial in 2008, and has returned this year to embark on an MSc leading to a PhD. Currently Irina Saltykova from the Siberian State Medical University is undertaking her Fellowship at Imperial, due to end in February. Maria Vasilieva Maria Vasilyeva is a medical doctor (2001) with a specialization in Allergy and Immunology (2003) and PhD in Oncology and Immunology (2006). She has a 5 years experience of practical work as an allergist-immunologist and also she has an experience of same laboratory methods (induced sputum assay, ELISA). Maria is a researcher for Central Research Laboratory of Siberian State Medical University (partner 29: SSMU). Her present research is focused on the immune mechanisms of opisthorchis infection and its relation to atopy. Opisthorchis felineus helminth infection is very common in Tomsk region (West Siberia, Russian Federation) and it appears to influence atopic disease prevalence in this region. Infectious background in conjunction with urban European-like and typical rural lifestyle give very good models of natural relationships between infectious and atopic diseases which are one of the major issues in the GABRIEL project. Immune mechanisms of opisthorchis infection and its relation to atopy in urban and rural areas in Tomsk region will be studied in the project of Siberian State Medical University (SSMU, Tomsk, Russia) in junction with the Department of Parasitology of Leiden University Medical Center (LUMC, Leiden, Netherlands). During Maria’s GABRIEL Fellowship in Netherlands she was based at Parasitology Department of Leiden University Medical Center under the supervision of Professor Maria Yazdanbakhsh. She has got 3-mounth training in cellular and molecular immunological techniques appropriate for the analysis of cell proliferation activity and immune system associated genes expression to be able to use these methods for the project realizing at the basis of Central Research Laboratory of Siberian State Medical University. Fellowship activities description A. Theoretical training. B. Laboratory techniques training. C. A specified short project aimed to compare whole blood and PBMC TLR ligands tolerance induction. This part of the training involved totally independent setting up of the project, data generation, data analysis and presentation. Conclusions The immuno-epidemiological project of Siberian State Medical University (SSMU, Tomsk, Russia) in junction with the Department of Parasitology of Leiden University Medical Center (LUMC, Leiden, Netherlands) will be carried out in an area with a special epidemiology of allergic disorders and Opistorchis felineus infection. Maria Vasilyeva had a 3-mounth GABRIEL Fellowship for the training in cellular and molecular immunological techniques appropriate for the analysis of cell proliferation activity and immune system associated genes expression. After training she will use these methods for the project realizing at the Central Research Laboratory of Siberian State Medical University. Giovanni Malerba The Project Bertrand Sudre Bertrand is a Physician (2003) with a specialization in Epidemiology and Environment (2004) and third year of PhD in environmental assessment in the research team Santé, Environnement Rural in Franche Comté (Besançon). He worked as Parasitologist in the Universitary hospital of Besançon and is now located at the UMR 6249 Chrono-environnement in Franche Comté University (http://chrono-environnement.univ-fcomte.fr/ ; Besançon – France ).involved in studying the exposure to biological component in the farm environment and the link with allergy protection. He is involved in the PASTURE study with reference to the composition of farm environment since 2003. His centre of interest is studying environmental exposures, infectious diseases and biostatistics. The project The farm environment can confer protection or imply risks for the development of asthma in several studies. A better understanding of the microbial exposures associated with these effects would therefore be warranted such as the advanced studies in rural environments of the GABRIEL project. A database on microbial compounds and pollens measured in repeated air samples from farms and rural homes in France, Germany and Switzerland (PASTURE Microbio-Study) offer the opportunity to get insight into the composition of microbial species present in the stables and in rural indoor environment and to relate them to characteristics of the respective farms. We will focus the work on analyses of fungal and bacterial species and pollen components associated with farm characteristics that have been found to confer protection or imply risks for asthma in previous studies. These results will be link with validation studies in the Gabriel project for the environmental assessment and could provide of relevant fungal and bacterial species to search in the settled dust from stables and indoor home in the advanced studies in rural environments of the GABRIEL project. Publications from the fellowship: JOURNAL : ALLERGY. Accepted for publication 24 November 2008
Link : http://www3.interscience.wiley.com/journal/122201883/abstract?CRETRY=1&SRETRY=0 Original article High levels of grass pollen inside European dairy farms: a role for the allergy-protective effects of environment?
B. Sudre 1 , M. Vacheyrou 1 , C. Braun-Fahrländer 2 , A.-C. Normand 1 , M. Waser 2 , G. Reboux 1 , P. Ruffaldi 1 , E. von Mutius 3 , R. Piarroux 1,4 and the PASTURE study group* ABSTRACT Background: There is evidence of an allergy protective effect in children raised on farm. It has been assumed that microbial exposure may confer this protection. However in farm, little attention has been given to the pollen level and to concomitant microbiological exposure, and indoor pollen concentrations have never been precisely quantified. Markus Ege The GABRIEL study has been set up to assess the relation between genetic and environmental determinants of asthma. In my previous work I had studied farm related exposures as specific environmental determinants for asthma. In this next step I wondered whether the protective effect of farming on asthma might be interacting with genetic effects. A subsample of the GABRIEL advanced studies had already been genotyped for the GABRIEL meta-analysis for asthma. Since detailed questionnaire information on farming exposures was available in these children, this population was ideal to study gene by farming environment interactions. Interactions are interesting because they may explain why genetic effects can only be observed in populations with or without an environmental exposure or may reveal genetic effects that might be missed when the interacting environmental exposure is unknown . Since genotyping and environmental assessment are cost-intensive the sample size and consequently the power of the interaction analysis was limited. Therefore I performed a power calculation and explored several methods to fully utilize the available power. As a first approach, I assessed genetic (SNPs) and environmental determinants of asthma separately and tested only significant determinants in interaction models. To save power significant SNPs were taken from the GABRIEL meta-analysis for childhood onset asthma provided by GABRIEL partner 32 (Florence Demenais, INSERM, France). Inspired by a paper by Murcray et al. (Am J Epidemiol 2009; 169: 219) I explored an alternative approach: The relevant environmental determinants for asthma were tested for associations with all SNPs of the genome wide association study (GWAS) irrespective of asthma. For the subsequent interaction analysis SNPs were selected for their (statistical) association with the respective environmental exposures. Towards the end of my fellowship I tried to modify this approach and to improve it in order to enhance power additionally. I am currently developing further methods and am confident that these will soon be applicable to the GABRIEL data set. Paul Cardenas I am a medical doctor (2006) with a specialization in Microbiology (2008) during which time I had the opportunity to apply numerous molecular biological techniques in the medical practice, especially I was focused in the analysis of nosocomial and community acquired infectious diseases using bacterial genotyping methods. More recently I have been involved in a Wellcome Trust funded birth cohort study, ECUAVIDA in Ecuador, run by Professor Philip Cooper, and set up with the purpose of investigating early environmental exposures associated with the development of allergic sensitization and atopic disease. Using clinical samples from infants living in tropics, I conducted metagenomic studies as part of a portfolio of work ongoing in one of the world-leading asthma genetics research groups based at Imperial College supported by GABRIEL Visiting Fellowship. My research, in the laboratory of Professors Bill Cookson and Miriam Moffatt at the NHLI at Imperial College involved an investigation of a) differences in pulmonary microbiota between infants, from the ECUAVIDA cohort, with and without early onset asthma using metagenomic techniques; b) differences in gene expression profiles (transcriptomics) in asthmatic cases and non-asthmatic controls from SCAALA Esmeraldas - a large Wellcome Trust-funded cross-sectional study examining the impact of migration on asthma risk. Interaction between mucosal microbiota and immune cells is central in the development of the immune system. Microbiota mediates mechanisms of immunological tolerance and it is essential to regulate mucosal inflammation; these variations could contribute in the development of atopic disease and asthma in children. Strikingly, we found that bacterial microbiota in oropharynx mucosa varied significantly in numbers and types of Phyla and Operational Taxonomic Units (OTUs) between healthy and asthmatic infants. Using cladistic and statistical analysis we found a higher prevalence of potentially pathogenic bacteria as Neisseria sp., Haemophilus sp. and Porphyromonas sp. in asthmatic children; and a higher prevalence of Firmicutes in controls which could be interpreted as a protective factor (healthy bacterial flora) in opposition to asthma development. This study will help to determine the impact of urbanization, vaccination prevalence and parasites early exposures in the prevalence of asthma in children living in tropics. Irina Saltikova I am a PhD-student at the Siberian State Medical University (Tomsk, Russia). I investigate genetic basis of allergic diseases complicated by Opisthorchis felineus live fluke invasion. Tomsk Region is a world centre of this helminth distribution, and it has been shown that its invasion significantly modifies course of allergic disease and influences epidemiological portrait of allergy in Siberia. My project goal is to establish a significance of interaction of genetic polymorphisms and O. felineus invasion in the development and clinical course of bronchial asthma. As a GABRIEL Fellow, I was trained in genome-wide expression profiling with use of Affymetrix Gene ST 1.0 microarray in Prof. W. Cookson and Prof. M.Moffatt lab in Imperial College London (UK). We aimed at identifying gene expression profiles in Siberian patients with mild and severe asthma of rare clinical phenotypes before and during the course of basic therapy. Among the severe asthma, "brittle" type I, therapeutically controlled, and low bronchial obstruction clinical phenotypes were studied. Two time points were investigated as a pilot stage, before therapy and 3 month after beginning the course. Preliminarily, we have found the significant influence of therapy on gene expression in mild patients and, less pronounced, but significant, in severe patients with controlled asthma. However, the effect of treatment on gene expression in patients with "brittle" asthma and asthma with low bronchial obstruction was elusive. This results give some insight into understanding of mechanism of severe asthma development, which is one of the goals of GABRIEL project. EU Cordis University of Munich Imperial College London Asthma UK back to top © GABRIEL 2006. All rights reserved. Website contact: Dana Finch d.finch@imperial.ac.uk Updated January 2010 | |