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European Molecular Biology Laboratory and XtalConcepts GmbH | Date: 2017-04-26

The present invention relates to a measurement cell which facilitates a small angle X-ray scattering measurement and facilitates dynamic light scattering measurements within the identical sample compartment of a sample holder. Light transportation means which are arranged and configured for transporting light of the light source towards the sample in the sample compartment and/or for transporting light scattered from the sample towards the detector are comprised. For example, a first and a second window which are optically transparent for the DLS light and the scattered light are presented. The first and second windows are provided at a sample holder which is specifically designed as a SAXS sample holder. Furthermore, a method of solution scattering for quality assessment of a sample is presented.

European Molecular Biology Laboratory | Date: 2017-04-26

The present invention deals with heterotrimeric AMP-activated protein kinase (AMPK) comprising a fluorophore pair wherein the conformational change can be measured by FRET. It represents an advanced tool to screen and identify AMPK interactors in vitro and in cells in vivo. Such invention can also be considered as a reporter of the cellular energy status as it allows the spatiotemporal monitoring, in situ, of fluctuations in the ratio of AMP and ADP versus ATP.

European Molecular Biology Laboratory | Date: 2017-06-07

The present invention relates to a method for producing at least one artificial piRNA, comprising determining an endogenous piRNA population in a cell of an organism of interest; selecting a sub-population of said endogenous piRNA population based on binding of a MILI protein and/or an equivalent PIWI protein to said sub-population; identifying the sequence of at least one piRNA as selected, attaching said at least one piRNA sequence as identified 5 to the sequence of the transcript of a gene of interest, in order to generate at least one piRNA template, and slicing said piRNA template through binding of a MILI protein to said template and subsequent slicing of said bound piRNA template following a binding of MILI protein and/or MIWI2 protein in order to generate at least one artificial piRNA. The method can be used to produce pharmaceutical compositions comprising at least one artificial piRNA as produced according to the invention. Other aspects relates to a method for silencing the expression of a gene of interest in an organism of interest, comprising administering to said organism an effective amount of a pharmaceutical composition according to the invention, and a method for produing a non-genetically modified organism having an artificially silenced expression of at least one gene of interest based on the method of the invention.

Leica and European Molecular Biology Laboratory | Date: 2017-06-07

In a light microscope (1) for cryomicroscopy comprising at least one objective (2) and a sample stage (3) having a cutout (7) for a coolable holder (8) for a sample carrier mount, wherein the cutout (7) is covered by a cover (6), the sample stage (3) is displaceable in two horizontal directions (4). The cover (6) lies on the sample stage (3) in a floating fashion and the objective (2) penetrates through a cutout (12) corresponding to the objective (2) in the cover (6). The method for cooling a holder (8) for a sample carrier mount in a light microscope (1) for cryomicroscopy by causing liquid nitrogen to flow through a cooling line (15) open at at least one end in the holder (8) is distinguished by the fact that the quantity of liquid nitrogen is dimensioned such that the entire nitrogen is present in gaseous form at the at least one open end (16) of the cooling line (15).

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-33-2015 | Award Amount: 30.12M | Year: 2016

The vision of EU-ToxRisk is to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project will focus on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. EU-ToxRisk extensively integrates the adverse outcome pathway (AOP)-based toxicity testing concept. Therefore, advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of AOPs and key events (KE). The project combines in silico tools and in vitro assays by computational modelling approaches to provide quantitative data on the activation of KE of AOP. This information, together with detailed toxicokinetics data, and in vitro-in vivo extrapolation algorithms forms the basis for improved hazard and risk assessment. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fit-for-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The test systems will be combined to a flexible service package for exploitation and continued impact across industry sectors and regulatory application. The proof-of-concept for the new mechanism-based testing strategy will make EU-ToxRisk the flagship in Europe for animal-free chemical safety assessment.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-01-2016 | Award Amount: 15.04M | Year: 2017

The complex interactions between genetic and non-genetic factors produce heterogeneities in patients as reflected in the diversity of pathophysiology, clinical manifestations, response to therapies, disease development and progression. Yet, the full potential of personalized medicine entails biomarker-guided delivery of efficient therapies in stratified patient populations. MultipleMS will therefore develop, validate, and exploit methods for patient stratification in Multiple Sclerosis, a chronic inflammatory disease and a leading causes of non-traumatic disability in young adults, with an estimated cost of 37 000 per patient per year over a duration of 30 years. Here we benefit from several large clinical cohorts with multiple data types, including genetic and lifestyle information. This in combination with publically available multi-omics maps enables us to identify biomarkers of the clinical course and the response to existing therapies in a real-world setting, and to gain in-depth knowledge of distinct pathogenic pathways setting the stage for development of new interventions. To create strategic global synergies, MultipleMS includes 21 partners and covers not only the necessary clinical, biological, and computational expertise, but also includes six industry partners ensuring dissemination and exploitation of the methods and clinical decision support system. Moreover, the pharmaceutical industry partners provide expertise to ensure optimal selection and validation of clinically relevant biomarkers and new targets. Our conceptual personalized approach can readily be adapted to other immune-mediated diseases with a complex gene-lifestyle background and broad clinical spectrum with heterogeneity in treatment response. MultipleMS therefore goes significantly beyond current state-of-the-art thereby broadly affecting European policies, healthcare systems, innovation in translating big data and basic research into evidence-based personalized clinical applications.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRADEV-04-2016 | Award Amount: 9.95M | Year: 2017

The EOSCpilot project will support the first phase in the development of the European Open Science Cloud (EOSC) as described in the EC Communication on European Cloud Initiatives [2016]. It will establish the governance framework for the EOSC and contribute to the development of European open science policy and best practice; It will develop a number of pilots that integrate services and infrastructures to demonstrate interoperability in a number of scientific domains; and It will engage with a broad range of stakeholders, crossing borders and communities, to build the trust and skills required for adoption of an open approach to scientific research . These actions will build on and leverage already available resources and capabilities from research infrastructure and e-infrastructure organisations to maximise their use across the research community. The EOSCpilot project will address some of the key reasons why European research is not yet fully tapping into the potential of data. In particular, it will: reduce fragmentation between data infrastructures by working across scientific and economic domains, countries and governance models, and improve interoperability between data infrastructures by demonstrating how data and resources can be shared even when they are large and complex and in varied formats, In this way, the EOSC pilot project will improve the ability to reuse data resources and provide an important step towards building a dependable open-data research environment where data from publicly funded research is always open and there are clear incentives and rewards for the sharing of data and resources.

Agency: European Commission | Branch: H2020 | Program: CSA | Phase: INFRADEV-03-2016-2017 | Award Amount: 4.97M | Year: 2017

The INFRAFRONTIER RI integrates European Mouse Clinics and the European Mouse Mutant Archive with the common goal to ensure access to mouse models for basic research of human health and disease, and to translate this knowledge into therapeutic approaches for the benefit of the European society. The expanded INFRAFRONTIER2020 network, coordinated by the INFRAFRONTIER GmbH, includes 3 SMEs and is strategically responding to the INFRADEV3 call with aligned objectives to advance the long-term sustainability which are 1) development of business models and a stable legal framework; 2) raise awareness of the INFRAFRONTIER RI; 3) provide bespoke services aligned with user demands; 4) promote best practices in mouse phenogenomics; 5) enhance robustness of the INFRAFRONTIER IT infrastructure and use of the EMMA strain resource; and 6) improve business processes. Towards achieving these objectives key INFRAFRONTIER2020 project deliverables are: INFRAFRONTIER Business Plan2.0, and business models for all services Stable legal framework built on the INFRAFRONTIER legal entity INFRAFRONTIER annual stakeholder conferences Customised mouse model and secondary phenotyping pilot services INFRAFRONTIER advanced training schools in mouse phenogenomics Reengineered EMMA Database2.0 system Annotated mouse models of human diseases Quality management system for the legal entity INFRAFRONTIER2020 will 1) enhance the sustainable operation of the INFRAFRONTIER RI; 2) continue to structure the ERA, 3) foster innovation, and 4) address major societal challenges in human health by customised service pilots supporting research into common and rare diseases. A sustainable INFRAFRONTIER RI will ensure the quality of deposited mice and support the reproducibility of biological results. Outreach efforts will raise awareness of resources and services and facilitate sustainable engagement with industry and global consortia such as the International Mouse Phenotyping Consortium

Spitz F.,European Molecular Biology Laboratory | Furlong E.E.M.,Genome Biology Unit
Nature Reviews Genetics | Year: 2012

Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development. © 2012 Macmillan Publishers Limited. All rights reserved.

Wennekamp S.,European Molecular Biology Laboratory
Nature reviews. Molecular cell biology | Year: 2013

The mechanisms underlying the appearance of asymmetry between cells in the early embryo and consequently the specification of distinct cell lineages during mammalian development remain elusive. Recent experimental advances have revealed unexpected dynamics of and new complexity in this process. These findings can be integrated in a new unified framework that regards the early mammalian embryo as a self-organizing system.

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