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Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.1-1 | Award Amount: 7.80M | Year: 2011

Glycosylation is a post-translational modification that enriches protein complexity and function. Dysregulation of glycosylation is associated with a wide range of diseases, including cancer, diabetes, as well as congenital, cardiovascular, immunological and infectious disorders. A number of studies identified potentially important glycan disease biomarkers. With regard to biotechnology, proper glycosylation of biologicals is important, as deviations in glycosylation are known to be associated with adverse drug reactions and reduced therapeutic efficacy. However, glycomics is significantly lagging behind genomics and proteomics, mainly due to the absence of high-throughput analytical methods which can reliably quantify a multitude of glycan structures in complex biological samples. We are confident that by coordinated efforts of leading European scientists in glycan analysis using HPLC, MS and CGE-LIF technologies this project will make a decisive step forward by developing real high-throughput tools for glycosylation analysis. By teaming up with leading European researchers in the field of genome wide association studies this project will perform validation of all methods on extremely well characterized set of samples resulting from the FP6 EuroSpan project. The addition of the newly generated glycome data to the pre-existing information about these individuals will enable development of methods for the systems biology approach analysis of the glycome which will integrate glycomic, genomic and environmental data about thousands of individuals. The same methods will also be adapted for quality control and monitoring in the production of biopharmaceuticals. Strong participation of SMEs in the project and close contacts with large industrial partners will ensure that research accomplishments achieved by collaboration between academic and industrial scientists are swiftly transformed into innovative products and services for the benefit of European industry.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-01-2016 | Award Amount: 16.02M | Year: 2017

The SYSCID consortium aims to develop a systems medicine approach for disease prediction in CID. We will focus on three major CID indications with distinct characteristics, yet a large overlap of their molecular risk map: inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis. We have joined 15 partners from major cohorts and initiatives in Europe (e.g.IHEC, ICGC, TwinsUK and Meta-HIT) to investigate human data sets on three major levels of resolution: whole blood signatures, signatures from purified immune cell types (with a focus on CD14 and CD4/CD8) and selected single cell level analyses. Principle data layers will comprise SNP variome, methylome, transcriptome and gut microbiome. SYSCID employs a dedicated data management infrastructure, strong algorithmic development groups (including an SME for exploitation of innovative software tools for data deconvolution) and will validate results in independent retrospective and prospective clinical cohorts. Using this setup we will focus on three fundamental aims : (i) the identification of shared and unique core disease signatures which are associated with the disease state and independent of temporal variation, (ii) the generation of predictive models of disease outcome- builds on previous work that pathways/biomarkers for disease outcome are distinct from initial disease risk and may be shared across diseases to guide therapy decisions on an individual patient basis, (iii) reprogramming disease - will identify and target temporally stable epigenetic alterations in macrophages and lymphocytes in epigenome editing approaches as biological validation and potential novel therapeutic tool. Thus, SYSCID will foster the development of solid biomarkers and models as stratification in future long-term systems medicine clinical trials but also investigate new causative therapies by editing the epigenome code in specific immune cells, e.g. to alleviate macrophage polarization defects.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-5 | Award Amount: 8.58M | Year: 2013

Pain-OMICS is a multidisciplinary consortium of leading clinical, academic and SME researchers in pain and different omics technologies. Genome-wide association studies identified a number of loci associated with pain, but the level of knowledge about underlying mechanisms of different pain syndromes as well as individual variation in the disease course remains inadequate. Pain-OMICS will capitalise on its existing high quality clinical, genetic, biochemical and pharmacological data and biological samples on over 5000 well characterised patients with low-back pain (LBP) and controls available to our EU and US clinical partners. We will exploit novel technological approaches made available through the expertise and global leading position of our analytical partners. These comprise cutting edge genomic, epigenomic, glycomic, and activomic approaches which reflect signal transduction and membrane dynamics. We believe that the inclusion of these complementary analyses will elucidate pathways through which acute LBP fails to resolve and becomes chronic LBP. In addition, these approaches will reveal pathways and biomarkers of chronic pain through which individual differences affects symptoms and response to therapy. Participation of leading clinics on both sides of the Atlantic will enable replication of all finding in at least three independent large cohorts, as well as in prospective study and a large twin cohort. A complex systems biology approach will be used to integrate, interrogate and understand this multidimensional dataset in order to achieve the aims of identifying novel diagnostic and prognostic biomarkers as well as new targets for therapeutic intervention. The track record of achievement of our partners coupled to participation of research-intensive SMEs is a strong indication that the ambitious work programme will be achieved and provides a framework for rapid translation of research discoveries into solutions for the benefit of large numbers of patients.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.1.2-1 | Award Amount: 6.81M | Year: 2011

Glycosylation patterns on glycoproteins and glycolipids are involved in the regulation of inter- and intracellular recognition events and alteration of such glycosylation has been observed in many diseases, notably in a variety of cancers. We propose that a systematic, large scale investigation in this area will provide a rich spectrum of novel and structurally diverse carbohydrate-based highly specific biomarkers. The aim of this project will be to address current bottlenecks in analytical techniques by developing an integrated multidisciplinary approach to glycobiomarker screening and analysis based on current state-of-the-art. We will bring together a number of complementary screening techniques developed in the individual partner laboratories, notably high-throughput LC-ms analysis of carbohydrates, lectins and carbohydrate arrays, to develop an overall workflow for the multiplex analysis of glycobiomarkers. Such carbohydrate-targeted methods will be combined with RNA/DNA and analysis (combining high throughput glycomics with genomics). It will be important to test the workflow against serum and tissue samples of healthy volunteer/cancer patients. In addition, we envisage that the project will generate new analytical tools that can be used in routine analysis of glycobiomarkers in the clinic, including diagnostic imaging. Some of the tools developed in this programme (lectins conjugated to nonoparticles) should also be useful for new quantitative imaging biomarkers for monitoring therapeutic effects and safety in cancer. The involvement of three SME partners will ensure that the technology is compatible with commercial applications.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.5-2 | Award Amount: 8.55M | Year: 2012

Inflammatory bowel diseases affect 0.8% of the Europeans, and are associated with high morbidity, definite mortality and an increasing economic burden. Current diagnostic tools and therapeutics for IBD are unsatisfactory. Development of biomarkers allowing insights into pathogenesis, prognosis and targeted therapy is a major unmet need. This programme addresses that need. IBD-BIOM is a multidisciplinary consortium of leading academic and industrial SME researchers in inflammatory bowel disease, genomics, glycomics, glycoproteomics and activomics. Recent genome-wide association studies performed by IBD-BIOM partners have identified nearly 100 genes associated with IBD, but clinical application of these is so far limited. IBD-BIOM will capitalise on its existing high quality clinical, genetic, biochemical and immunological data and biological samples on over 6000 very well characterised IBD patients and controls by exploiting novel technological approaches made available through the expertise and global leading position of IBD-BIOM partners. These comprise cutting edge epigenetic, glycomic, glycoproteomic and activomic approaches which were all previously reported to be associated with inflammation and disturbances to the immune system. The inclusion of these complementary analyses in the diagnostics of IBD should also facilitate elucidation of pathways through which environmental exposures influence IBD risk and progression. A complex systems biology approach will be used to integrate, interrogate and understand this multidimensional dataset to identify novel early diagnostic and prognostic biomarkers and new targets for therapeutic intervention. The track record of achievement of IBD-BIOM partners coupled to the central and leading positions of the research-intensive SME partners in IBD-BIOM is a strong indication that the ambitions work programme will be achieved and a framework to facilitate swift conversion of research discoveries into commercial products.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.1.1-3 | Award Amount: 7.88M | Year: 2012

MIMOmics develops statistical methods for the integrated analysis of metabolomics, proteomics, glycomics and genomic datasets in large studies. Our project is based on our involvement in studies participating in EU funded projects, i.e. GEHA, IDEAL, Mark-Age, ENGAGE and EuroSpan. In these consortia the primary goal is to identify molecular profiles that monitor and explain complex traits with novel findings so far. Support for methodological development is missing. The state-of-the-art methodology does not match by far the complexity of the biological problem. Complex data are being analysed in a rather simple way which misses the opportunity to uncover combinations of predictive profiles among the omics data. The objectives of MIMOmics are: to develop a statistical framework of methods for all analysis steps needed for identifying and interpreting omics-based biomarkers; and to integrate data derived from multiple omics platforms across several study designs and populations. Specific steps include: experimental design; pipelines for data gathering; cleaning of noisy spectra; predictive modeling of biomarkers; meta analysis; and causality assessment. To enhance our understanding, systems approaches will be considered for pathways and structural modelling of biological networks. The major challenge in the joint analysis of omics datasets will be to develop methods that deal with the high dimensionality, noisy spectral data, heterogeneity, and structure of these datasets. To perform these tasks successfully we bring together established EU academic and industrial researchers in metabolomics, glycomics, biostatistics, bioinformatics, scientific computing and epidemiology, with complementary expertise. A key feature of our project is the validation of novel methodology by performing a proof of principle (Metabolic Health) . Special effort will be made for rapid uptake of methods by communication with associated consortia and development of user-friendly software


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.29M | Year: 2015

Colorectal cancer (CRC) is a major worldwide cancer burden with about 1.4 million cases in 2012 and an annual mortality of approximately 700,000. Early detection is crucial as treatment is most efficient in early stages where population based screenings could substantially reduce incidence and mortality. Current screening techniques are invasive or lack sensitivity and specificity. Moreover, the molecular mechanisms leading to the formation of different antigens suggested as CRC biomarkers and potential therapeutic targets are poorly understood, especially with regard to carbohydrate-based molecules, such as glycans. Enhancing our understanding of the structure-function relationship of glycosylation in CRC could lead to the discovery of improved diagnostic and prognostic biomarkers and pave the way for nov-el therapeutic targets. Building on an established network of analysts with many years of experience in (glyco)proteomics and biomarker research, in collaboration with colleagues in the field of glycobiology and glyco-immunology, GlyCoCan will develop new methods, and use current state of the art methods, to investigate the role of glycosylation in many different aspects of CRC. The GlyCoCan multi-disciplinary network will principally be a training programme with a substantial industrial focus on technology transfer and teaching of internationally adopted biopharma regulations (GMP, ISO9001, ICH guidelines). The underlying specific research objectives will be addressed within individual ESR projects, giving rise to a generation of ESRs whose main focus is investigating and tackling the challenges of the role of glycosylation within CRC and other diseases. The network will address the currently unmet need for glycosylation researchers with an inter-disciplinary perspective to fully exploit the immense potential of the young scientific field of glyco-oncology and to set them on a path to successful and productive careers in academic and industrial collaborations.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2012-IAPP | Award Amount: 1.82M | Year: 2013

The main aim of the HTP-GlycoMet proposal is to develop technologies, which will enable high-throughput analysis of glycosylation of individual proteins from body fluids and cell membranes and apply them to understand some key processes in immunity and infections. Glycan analysis is extremely demanding from both technological and conceptual aspect and (beside one study performed by partners in this proposal) large-scale studies of glycosylation of individual proteins were not attempted previously. However, we are confident that by successfully combining complementary expertise in the (i) production of specialised monolithic chromatographic tools for high-throughput fractionation of complex biological fluids (BIA-SEP), (ii) purification of proteins from body fluids and membrane proteins (UNI-RI), (iii) high-throughput glycomic analysis by use of chromatography (Genos) and multiplexed capillary gel electrophoresis (MPI) and (iv) expertise in the field of viral immunology (MEDRI) we can achieve significant progress in this direction. All our partners are recognized leaders who already made significant progress beyond the state of the art in their respective fields. Through HTP-GlycoMet project we will organise secondments on all levels (MER, ER, ESR) to capitalize on synergistic effects of this interdisciplinary and transnational collaboration. In addition to the generation of new knowledge and the development of new innovative technologies, we will also achieve significant transfer of knowhow between academic and industrial partners. Our SME partners also expect to develop new lines of products and services through the HTP-GlycoMet programme, but also through future collaboration with HTP-GlycoMet partners beyond the lifetime of this project.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-EID | Phase: MSCA-ITN-2016 | Award Amount: 1.55M | Year: 2016

GlySign is a research training network for the translation of glycomic clinical biomarkers for Precision Medicine (PM). Complex, distinctive changes occur in the glycomics profiles or - Glycan Signatures - of human glycoproteins during progression of many chronic diseases including cancer and inflammatory conditions. The three beneficiaries of the GlySign Consortium have been instrumental in contributing to knowledge in this field through development of glycomics technology and discovery of clinically important novel glycan biomarkers in a variety of diseases. Glycan signatures have great potential for adding useful diagnostic and prognostic information in PM. However, advancement of this field is slow because (a) glycans have immense structural complexity resulting in major technical challenges for their analysis and (b) there is a lack of experts with required glycoanalytical skills. GlySign will address this gap by training six young scientists within an innovative training-by-research programme with high industrial-academic mobility to eventually push forward the translation of novel glycomics-based diagnostic tools into clinical practice. This will be achieved by further developing a range of selective and sensitive glycomics technologies for the analysis of samples from patients and healthy controls in close collaboration between industry/academia as well as clinical chemists and clinicians who will be the end users of GlySigns final products. To this end, we will focus the training on clinical glycomics applied to four model diseases implicating changes in the glycosylation of circulating proteins specific to disease progression or subtype, i.e. diabetes, prostate cancer, fetal and neonatal alloimmune thrombocytopenia and rheumatoid arthritis. Due to its strong industrial and translational focus, GlySign will, moreover, fill a current gap in the market by establishing new in vitro diagnostic platforms for clinical exploitation of glycomic biomarkers for PM.

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