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Enot D.P.,Biocrates Life Sciences
Methods in molecular biology (Clifton, N.J.) | Year: 2011

The broad view of the state of biological systems cannot be complete without the added value of integrating proteomic and genomic data with metabolite measurement. By definition, metabolomics aims at quantifying not less than the totality of small molecules present in a biofluid, tissue, organism, or any material beyond living systems. To cope with the complexity of the task, mass spectrometry (MS) is the most promising analytical environment to fulfill increasing appetite for more accurate and larger view of the metabolome while providing sufficient data generation throughput. Bioinformatics and associated disciplines naturally play a central role in bridging the gap between fast evolving technology and domain experts. Here, we describe the strategies to translate crude MS information into features characteristics of metabolites, and resources available to guide scientists along the metabolomics pipeline. A particular emphasis is put on pragmatic solutions to interpret the outcome of metabolomics experiments at the level of signal processing, statistical treatment, and biochemical understanding.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.2.2-2 | Award Amount: 3.88M | Year: 2012

Healthy brain ageing is a major determinant of quality life-long health, allowing integration into society at all ages. Human epidemiological and animal studies indicate that in addition to life style and genetic factors, environmental influences in prenatal life have a major impact on brain ageing and age-associated brain disorders. We hypothesize that: (1) prenatal stress programs early brain ageing; (2) this predisposes to age-associated brain diseases including cognitive decline and stroke; (3) epigenetic changes affecting glucocorticoid receptor (GR) sensitivity, altered autonomic nervous system (ANS) reactivity and cerebrovascular tone are important mediators of these processes, (4) these changes represent targets for diagnosis and therapeutic interventions. Our consortium has unique access to well-defined human and non-human primate cohorts (age range 25-115 y equivalents) that have been exposed to different types of prenatal stress. For experimental analysis of mechanisms of prenatal programming, we apply innovative techniques to characterize brain ageing, namely MRI based volumetry, non-linear analysis of EEG and ANS, advanced molecular techniques including epigenetics and metabolomics and neuropsychological and behavioral tests. Human subjects, non-human primates and rodents (including transgenic models) exposed to maternal stress, glucocorticoids or undernutrition are examined in order to: (1) determine structural (MRI based volumetry) and functional (metabolomics, brain function, cerebrovascular tone) indicators of brain age, (2) relate them to susceptibility to stroke and cognitive decline, (3) determine to what extent GR resistance, stress sensitivity, and cerebrovascular contractility mediate premature brain ageing and disease susceptibility; and, (4) dissect mechanisms and pharmacological interventions relevant for aged subjects. Data from the study allow to identify subjects at risk for premature brain ageing and to initiate interventional therapy.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.2-2 | Award Amount: 7.85M | Year: 2011

Biomarkers are considered as tools to enhance cardiovascular risk estimation. However, the value of biomarkers on risk estimation beyond European risk scores, their comparative impact among different European regions and their role in the drive towards personalised medicine remains uncertain. Based on harmonised and standardised European population cohorts we have built significant research collaboration, expertise and infrastructure in the EU. We will apply highly innovative SME-driven technologies and perform large-scale biomarker determination to assess the predictive value of existing and emerging biomarkers. Selection of emerging biomarkers will be based on integrated cutting-edge quantitative proteomic, transcriptomic, metabolomic, and miRNomic datasets established by private and public consortium members that will be disclosed to this consortium. Existing biomarkers will be selected based on non-redundancy and their association with cardiovascular risk and phenotypes. After SME-guided development of innovative assay systems biomarkers will be tested and validated in a stepwise fashion among European populations in primary and secondary prevention. In addition to their impact on risk prediction, their association with lifestyle determinants and cardiovascular phenotypes assessed by ultrasound and MRI technique will be evaluated. We will establish a BiomarCaRE panel which leads to improved disease prediction among different European populations. International collaborations with world-class clinical trial investigators will add data on the interaction of the BiomarCaRE panel with risk-lowering medication and lifestyle changes. The outcome of SME-driven technology development and clinical validation will undergo a medical technology assessment. The determination of cost-effectiveness will guide further clinical evaluation. These studies will reveal new methods of improved cardiovascular risk estimation and will open the path towards personalised medicine.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: KBBE.2011.2.2-02 | Award Amount: 7.84M | Year: 2012

NutriTech will build on the foundations of traditional human nutrition research using cutting-edge analytical technologies and methods to comprehensively evaluate the diet-health relationship and critically assess their usefulness for the future of nutrition research and human well-being. Technologies include genomics, transcriptomics, proteomics, metabolomics, laser scanning cytometry, NMR based lipoprotein profiling and advanced imaging by MRI/MRS. All methods will be applied in an integrated manner to quantify the effect of diet on phenotypic flexibility, based on metabolic flexibility (the capacity for the organism to adapt fuel oxidation to fuel availability). However, NutriTech will move beyond the state-of-the-art by applying these integrated methods to assess the underlying and related cell biological and genetic mechanisms and multiple physiological processes of adaptation when homeostasis is challenged. Methods will in the first instance be evaluated within a human intervention study, and the resulting optimal methods will be validated in a number of existing cohorts against established endpoints. NutriTech will disseminate the harmonised and integrated technologies on a global scale by a large academic network including 6 non-EU partners and by providing an integrated and standardised data storage and evaluation platform. The impact of NutriTech will be multifold and exploitation is crucial as major breakthroughs from our technology and research are expected. This will be achieved by collaboration with a consortium of 8 major food industries and by exploitation of specific technologies by our 6 SME partners. Overall, NutriTech will lay the foundations for successful integration of emerging technologies intro nutrition research.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-1 | Award Amount: 8.33M | Year: 2014

Asymptomatic vascular damage accumulates for years before patients are identified and subjected to therapeutic measures. The limited knowledge on early vascular disease pathophysiology is reflected in the lack of therapeutic options. SysVasc aims to overcome this limitation by mounting a comprehensive systems medicine approach to elucidate pathological mechanisms, which will yield molecular targets for therapeutic intervention. The consortium is based on established multidisciplinary European research networks, including specialists in pre-clinical and clinical research, omics technologies, and systems biology from research intensive SMEs and academia; partners synergistically provide access to an extensive number of selected population-based cohorts and associated datasets, cutting edge modeling and simulation methods, and established cardiovascular disease (CVD) animal models and patient cohorts. The coordinated application of these tools and know-how will identify pathophysiological mechanisms and key molecules responsible for onset and progression of CVD and validate their potential to serve as molecular targets for therapeutic intervention. To this end, the consortium will also use unique resources to evaluate molecular homology between the available model systems and human disease, which will yield reliable essential preclinical research tools to explore proof of concepts for therapeutic intervention studies and ultimately translate relevant results into novel therapeutic approaches. Collectively, SysVasc will identify and validate novel biology-driven key molecular targets for CVD treatment. Major scientific, societal and economic impact is expected including, but not limited to, providing a valuable resource to further CVD research, and enhance competitiveness of participating SMEs and European health industry in general by translating knowledge into innovative services in therapeutic target and drug research.

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