719 research outputs found

    Fighting the Diseases of the Future

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    Infectious disease is one of the greatest threats facing the world in the decades to come: unpredictable, fast-moving, difficult to track, and potentially more deadly than anything we’ve ever seen before. Rudi Balling, a German geneticist and director of the Luxembourg Centre for Systems Biomedicine, says the solutions to the epidemics of the future are cooperation be- tween scientists and a holistic approach to biology that accounts for the complexities of today’s world

    EATRIS Infrastructure Accelerates Translation

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    peer reviewedEfficient translation of research discoveries into clinical application is essential to improve human health and maintain Europe’s competitiveness in biomedical research and in health industry. A major bottleneck is the lack and the frag- mented nature of research infrastructure and know-how, leading to unacceptable delays or preventing of the development of new innovative medicines. The aim of EATRIS, European Advanced Translational Research InfraStructure in Medicine, is to fill this gap by developing a pan-European research infrastructure

    Author response

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    Detecting pathogens and mounting immune responses upon infection is crucial for animal health. However, these responses come at a high metabolic price (McKean and Lazzaro, 2011, Kominsky et al., 2010), and avoiding pathogens before infection may be advantageous. The bacterial endotoxins lipopolysaccharides (LPS) are important immune system infection cues (Abbas et al., 2014), but it remains unknown whether animals possess sensory mechanisms to detect them prior to infection. Here we show that Drosophila melanogaster display strong aversive responses to LPS and that gustatory neurons expressing Gr66a bitter receptors mediate avoidance of LPS in feeding and egg laying assays. We found the expression of the chemosensory cation channel dTRPA1 in these cells to be necessary and sufficient for LPS avoidance. Furthermore, LPS stimulates Drosophila neurons in a TRPA1-dependent manner and activates exogenous dTRPA1 channels in human cells. Our findings demonstrate that flies detect bacterial endotoxins via a gustatory pathway through TRPA1 activation as conserved molecular mechanism.sponsorship: Vlaams Instituut voor Biotechnologie Alessia Soldano Luis Franco Guangda Liu Natalia Mora Emre Yaksi Bassem A Hassanr Fonds Wetenschappelijk Onderzoek G.0702.12 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0077.15 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0680.10 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0681.10 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0503.12 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0654.15 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0761.10N Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0596.12 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0565.07 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar KU Leuven GOA/14/011 Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar European Commission IUAP P7/13 Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekensr KU Leuven OT/12/091 Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar KU Leuven PF-TRPLe Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talavera (Vlaams Instituut voor Biotechnologie, Fonds Wetenschappelijk Onderzoek|G.0702.12, Fonds Wetenschappelijk Onderzoek|G.0077.15, Fonds Wetenschappelijk Onderzoek|G.0680.10, Fonds Wetenschappelijk Onderzoek|G.0681.10, Fonds Wetenschappelijk Onderzoek|G.0503.12, Fonds Wetenschappelijk Onderzoek|G.0654.15, Fonds Wetenschappelijk Onderzoek|G.0761.10N, Fonds Wetenschappelijk Onderzoek|G.0596.12, KU Leuven|GOA/14/011, KU Leuven|OT/12/091, European Commission|IUAP P7/13, KU Leuven PF-TRPLe)status: Publishe

    The role of regulatory T cells in neurodegenerative diseases.

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    peer reviewedA sustained neuroinflammatory response is the hallmark of many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, and HIV-associated neurodegeneration. A specific subset of T cells, currently recognized as FOXP3(+) CD25(+) CD4(+) regulatory T cells (Tregs), are pivotal in suppressing autoimmunity and maintaining immune homeostasis by mediating self-tolerance at the periphery as shown in autoimmune diseases and cancers. A growing body of evidence shows that Tregs are not only important for maintaining immune balance at the periphery but also contribute to self-tolerance and immune privilege in the central nervous system. In this article, we first review the current status of knowledge concerning the development and the suppressive function of Tregs. We then discuss the evidence supporting a dysfunction of Tregs in several neurodegenerative diseases. Interestingly, a dysfunction of Tregs is mainly observed in the early stages of several neurodegenerative diseases, but not in their chronic stages, pointing to a causative role of inflammation in the pathogenesis of neurodegenerative diseases. Furthermore, we provide an overview of a number of molecules, such as hormones, neuropeptides, neurotransmitters, or ion channels, that affect the dysfunction of Tregs in neurodegenerative diseases. We also emphasize the effects of the intestinal microbiome on the induction and function of Tregs and the need to study the crosstalk between the enteric nervous system and Tregs in neurodegenerative diseases. Finally, we point out the need for a systems biology approach in the analysis of the enormous complexity regulating the function of Tregs and their potential role in neurodegenerative diseases

    Fundamenta Et Deductiones Eorum, Quae in Discursu succincte prolata, & Eruditis Scrupulum relinquere poterant, inter mille occupationes rudi Minerva congesta

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    FUNDAMENTA ET DEDUCTIONES EORUM, QUAE IN DISCURSU SUCCINCTE PROLATA, & ERUDITIS SCRUPULUM RELINQUERE POTERANT, INTER MILLE OCCUPATIONES RUDI MINERVA CONGESTA Fundamenta Et Deductiones Eorum, Quae in Discursu succincte prolata, & Eruditis Scrupulum relinquere poterant, inter mille occupationes rudi Minerva congesta ([1]) Titelseite ([1]) Text (1) Zugabe (52) Additio ([1]) Verzeichnuß der ienigen Bücher oder Tractätlein die ich bißhero hab in den Truck kommen lassen ([5]) Ad Lectorem. Praeter Errata Typographica ... ([5]) Zur Nachricht ([6]

    Computational systems biology approaches for Parkinson's disease

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    peer reviewedParkinson’s disease (PD) is a prime example of a complex and heterogeneous disorder, characterized by multifaceted and varied motor- and non-motor symptoms and different possible interplays of genetic and environmental risk factors. While investigations of individual PD-causing mutations and risk factors in isolation are providing important insights to improve our understanding of the molecular mechanisms behind PD, there is a growing consensus that a more complete understanding of these mechanisms will require an integrative modeling of multifactorial disease-associated perturbations in molecular networks. Identifying and interpreting the combinatorial effects of multiple PD-associated molecular changes may pave the way towards an earlier and reliable diagnosis and more effective therapeutic interventions. This review provides an overview of computational systems biology approaches developed in recent years to study multifactorial molecular alterations in complex disorders, with a focus on PD research applications. Strengths and weaknesses of different cellular pathway and network analyses, and multivariate machine learning techniques for investigating PD-related omics data are discussed, and strategies proposed to exploit the synergies of multiple biological knowledge and data sources. A final outlook provides an overview of specific challenges and possible next steps for translating systems biology findings in PD to new omics-based diagnostic tools and targeted, drug-based therapeutic approaches.FNR7643563 > Rudi Balling > Mito-PD > Mitochondrial Endophenotypes Of Pd > 01/01/2015 > 31/12/2017 > 201

    Rudi Balling

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    Revolutionizing medicine in the 21(st) century through systems approaches

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    peer reviewedPersonalized medicine is a term for a revolution in medicine that envisions the individual patient as the central focus of healthcare in the future. The term "personalized medicine", however, fails to reflect the enormous dimensionality of this new medicine that will be predictive, preventive, personalized, and participatory-a vision of medicine we have termed P4 medicine. This reflects a paradigm change in how medicine will be practiced that is revolutionary rather than evolutionary. P4 medicine arises from the confluence of a systems approach to medicine and from the digitalization of medicine that creates the large data sets necessary to deal with the complexities of disease. We predict that systems approaches will empower the transition from conventional reactive medical practice to a more proactive P4 medicine focused on wellness, and will reverse the escalating costs of drug development an will have enormous social and economic benefits. Our vision for P4 medicine in 10 years is that each patient will be associated with a virtual data cloud of billions of data points and that we will have the information technology for healthcare to reduce this enormous data dimensionality to simple hypotheses about health and/or disease for each individual. These data will be multi-scale across all levels of biological organization and extremely heterogeneous in type - this enormous amount of data represents a striking signal-to-noise (S/N) challenge. The key to dealing with this S/N challenge is to take a "holistic systems approach" to disease as we will discuss in this article

    Parkinson’s disease mouse models in translational research

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    peer reviewedAnimal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson's disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research
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