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Berlin, Germany

Herberth G.,Helmholtz Center for Environmental Research | Bauer M.,Helmholtz Center for Environmental Research | Gasch M.,Helmholtz Center for Environmental Research | Hinz D.,Helmholtz Center for Environmental Research | And 9 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014

Background There is evidence that microRNAs (miRNAs) are sensitive to environmental stressors, including tobacco smoke. On the other hand, miRNAs are involved in immune regulation, such as regulatory T (Treg) cell differentiation. The aim of the present study was to investigate the association between prenatal tobacco smoke exposure, miRNAs, and Treg cell numbers. Methods Within a prospective mother-child study (Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk), we analyzed the expression of miR-155 and miR-223 together with Treg cell numbers in maternal blood during pregnancy, as well as in cord blood (n = 441). Tobacco smoke exposure was assessed based on questionnaire answers and maternal urine cotinine levels. Additionally, the concentration of smoking-related volatile organic compounds was measured in dwellings of study participants. Results Both maternal and cord blood miR-223 expressions were positively correlated with maternal urine cotinine levels. An association was also found between maternal miR-223 expression and indoor concentrations of benzene and toluene. High miR-223 expression was associated with lower Treg cell numbers in maternal and cord blood. Furthermore, children with lower Treg cell numbers at birth had a higher risk of atopic dermatitis during the first 3 years of life. The concentration of the toluene metabolite S-benzylmercapturic acid in maternal urine was associated with decreased cord blood, but not maternal blood, miR-155 expression. A relationship between miR-155 expression and Treg cell numbers was not found. Conclusions For the first time, we show that maternal tobacco smoke exposure during pregnancy correlates with the level of miRNA-223 expression in blood, with an effect on children's cord blood Treg cell numbers and subsequent allergy risk. © 2013 American Academy of Allergy, Asthma & Immunology. Source

The present invention relates to a method, in particular an in vitro method for identifying a subgroup of natural killer cells of a mammal, preferably CD3, non T-lymphocyte derived NK cells, which often express the surface proteins CD56 and/or CD16, comprising analyzing the accessibility of the genomic DNA for OSBPL, such as OSBPL5, to bisulfite conversion and/or the methylation status of at least one CpG position in the genes for OSBPL, such as OSBPL5, in particular in their upstream and/or downstream regulatory regions, the promoter, introns, exons and introns exon borders and other conserved regions of said genes, wherein an increase of the accessibility of the genomic DNA and/or a demethylation in the sample as analyzed is indicative for said subgroup of NK cells. The analyses according to the invention can identify CD56+ cells and distinguish them from all other cells such as, for example, either CD56 and/or CD56 bright cells. The methods of the present invention are useful for the identification, the detection, the quantification and quality assurance and control of NK cells. Furthermore, the present invention relates to a kit for performing the above methods as well as respective uses of the inventive methods or kits. The present invention furthermore provides an improved method for analysing the accessibility of the genomic DNA for OSBPL, such as OSBPL5, to bisulfite conversion and/or an analysis of the methylation status of at least one CpG position in the genes for OSBPL, such as OSBPL5, allowing for a precise analysis of both optimally and even from sub-optimal quality samples, such as non-freshly obtained blood, tissue or serum samples.

The present invention relates to a method, in particular an in vitro method, for identifying CD8 positive subpopulations of a mammal, wherein said method comprises analyzing the bisulfite convertibility of at least one CpG position in the CD8 beta and CD8 alpha cell specific bisulfite convertibility gene region according to SEQ ID No. 1 and 2, wherein a bisulfite convertibility of at least one CpG position in said gene regions is indicative for a CD3+CD8+ and/or CD3+/CD8+ cell. The analyses according to the invention can identify CD3+CD8+ and/or CD3+/CD8+ cells on an epigenetic level and distinguish them from all other cells in complex samples, such as, for example, other blood cells.

Agency: Cordis | Branch: FP7 | Program: NoE | Phase: SEC-2011.7.4-1 | Award Amount: 8.18M | Year: 2012

The EUROFORGEN-NoE proposal aims to develop a network of excellence for the creation of a European Virtual Centre of Forensic Genetic Research. Forensic genetics is a highly innovative field of applied science with a strong impact on the security of citizens. However, the genetic methods to identify offenders as well as the creation of national DNA databases have caused concerns to the possible violation of privacy rights. Furthermore, studies to assess the societal dimension of security following the implementation of even more intrusive methods such as the genetic prediction of externally visible characteristics are highly relevant for their public acceptance. The network includes some of the leading groups in European forensic genetic research. It aims to create a closer integration of existing collaborations, as well as establishing new interactions in the field of security, as all key players are addressed: scientists, stakeholders, end-users, educational centres and scientific societies. Only if a long-term collaborative network can be established it will become possible to connect all scientific groups active in the field of forensic genetics, and to initiate a sustained effort covering all aspects of research. These efforts have to be combined with identifying and selecting the most innovative ideas to meet the challenges of analyzing biological crime scene samples compromised by degradation or indentified as mixtures of traces from multiple human sources. The proposal integrates five working packages. WP 1 is devoted to management and coordination. WP 2 will lead the activities aimed at the creation of the virtual centre of research. WP 3 will carry out exemplar projects as models of collaboration and integration of cutting edge research, later complemented by a competitive call for new research projects. The societal dimension of security as well as the ethical and legal aspects wil be addressed in WP 4, whereas WP 5 is devoted to education and training.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 2.80M | Year: 2015

The mission of EpiPredict is to train a multidisciplinary cohort of young researchers in a new approach to fully exploit the epigenetics of complex diseases. The 12 early-stage researchers (ESRs) will focus on a narrowly defined case, Tamoxifen-induced resistance in Estrogen Receptor positive (ER\) breast cancer, considering five resistance interacting pathways. Given the frequent Tamoxifen treatment failure, resistance prevention and reversal is an urgent clinical problem that is central in EpiPredict. The EpiPredict intersectorial training programme employs a timely systems medicine approach combining next-generation systematic epigenetic, gene/protein profiling with innovative gene-specific epigenetic interference technologies for iterative computational modelling. Together the ESRs will identify key epigenetic changes underlying Tamoxifen induced resistance. This will provide an important step towards diagnostic markers/tools to predict treatment outcome and response monitoring setting the scene for breast cancer personalized medicine. The fellows will be trained by experts from 6 academic and 2 non-academic beneficiaries and 7 partner organizations (1 academic, 6 non-academic including industrial/socio-public parties) and 5 visiting scientists, from fields ranging from epigenetics to both computation and medicine. Strong involvement of the private sector ensures exploitation of EpiPredict achievements and exposure of the ESRs to an entrepreneurial mindset. The cohort of supradisciplinary researchers represents a new generation of research leaders equipped to address complex diseases whilst taking personalized patient aspects into consideration. They will be equipped to compete successfully and succeed in their personal careers. EpiPredict will boost academia and pharma/biotech environments, providing extra impulses to drive European translational science, systems medicine, pharmaceutical industry, and Medical ICT offering ample job opportunities.

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