Steinau an der Strasse, Germany
Steinau an der Strasse, Germany

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Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.1.3-1 | Award Amount: 15.99M | Year: 2013

HeCaToS aims at developing integrative in silico tools for predicting human liver and heart toxicity. The objective is to develop an integrated modeling framework, by combining advances in computational chemistry and systems toxicology, for modelling toxic perturbations in liver and heart across multiple scales. This framework will include vertical integrations of representations from drug(metabolite)-target interactions, through macromolecules/proteins, to (sub-)cellular functionalities and organ physiologies, and even the human whole-body level. In view of the importance of mitochondrial deregulations and of immunological dysfunctions associated with hepatic and cardiac drug-induced injuries, focus will be on these particular Adverse Outcome Pathways. Models will be populated with data from innovative in vitro 3D liver and heart assays challenged with prototypical hepato- or cardiotoxicants; data will be generated by advanced molecular and functional analytical techniques retrieving information on key (sub-)cellular toxic evens. For validating perturbed AOPs in vitro in appropriate human investigations, case studies on patients with liver injuries or cardiomyopathies due to adverse drug effects, will be developed, and biopsies will be subjected to similar analyses. Existing ChEMBL and diXa data infrastructures will be advanced for data gathering, storing and integrated statistical analysis. Model performance in toxicity prediction will be assessed by comparing in silico predictions with experimental results across a multitude of read-out parameters, which in turn will suggest additional experiments for further validating predictions. HeCaToS, organized as a private-public partnership, will generate major socioeconomic impact because it will develop better chemical safety tests leading to safer drugs, but also industrial chemicals, and cosmetics, thereby improving patient and consumer health, and sustaining EUs industrial competitiveness.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2012.2.1.2-3 | Award Amount: 3.67M | Year: 2012

The aim of CASyM is a combined large scale effort to sustainably implement Systems Medicine across Europe. For that purpose CASyM will function as a managing and coordinating platform in bringing together a critical mass of relevant European stakeholders such as Systems Biology scientists, clinicians, programme managers, industry/SMEs as well as healthcare providers and patient organizations. The goal of that initial nucleus of experts is the development of a strategy to implement the Systems Biology approach into medical practice and research within the 4 years duration of CASyM. For this purpose it is essential that the involved communities build a vision and coordinated strategy. Our joint effort gathers extensive experience in the coordination and realization of such a new, large-scale European effort, thereby providing the basis for an advanced future medicine. The output of CASyM will be a conceptual framework defining the remits, milestones, mechanisms and metrics for the implementation of Systems Medicine. The development of this framework will overcome competitive barriers and proceed to produce a European roadmap for Systems Medicine as concerted project result.


Eickhoff H.,Scienion | Malik A.,Microdiscovery GmbH
Advances in Biochemical Engineering/Biotechnology | Year: 2013

A technology for protein microarrays in 96 well microplates has been developed as a widely adoptable platform for multiplexed protein based diagnostics. Procedures for protein microarray manufacturing, immobilization, assay optimization and optical detection methods were developed. Using a clever combination of state of the art technologies, a versatile platform that works with peptides, proteins and antibodies as capture agents in a scalable format for planar arrays is described. © Springer-Verlag Berlin Heidelberg 2013.


Gurumurthy R.K.,Max Planck Institute for Infection Biology | Maurer A.P.,Max Planck Institute for Infection Biology | Machuy N.,Max Planck Institute for Infection Biology | Hess S.,Max Planck Institute for Infection Biology | And 6 more authors.
Science Signaling | Year: 2010

Chlamydiae are obligate intracellular bacterial pathogens that have a major effect on human health. Because of their intimate association with their host, chlamydiae depend on various host cell functions for their survival. Here, we present an RNA-interference-based screen in human epithelial cells that identified 59 host factors that either positively or negatively influenced the replication of Chlamydia trachomatis (Ctr). Two factors, K-Ras and Raf-1, which are members of the canonical Ras-Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway, were identified as central components of signaling networks associated with hits from the screen. Depletion of Ras or Raf in HeLa cells increased pathogen growth. Mechanistic analyses revealed that ERK was activated independentlyof K-Ras and Raf-1. Infection with Ctr led to the Akt-dependent, increased phosphorylation (and inactivation) of Raf-1 atserine-259. Furthermore, phosphorylated Raf-1 relocalized from the cytoplasm to the intracellular bacterial inclusion in an Akt- and 14-3-3β-dependent manner. Together, these findings not only show that Chlamydia regulates components of an important host cell signaling pathway, but also provide mechanistic insights into how this is achieved. Copyright 2008 by Association for the Advancement of Science, 1200 New York Avenue, NW, Wa the American Association for the Advancement of Science; all rights reserved.


Bartfeld S.,Max Planck Institute for Infection Biology | Hess S.,Max Planck Institute for Infection Biology | Hess S.,Hannover Medical School | Bauer B.,Max Planck Institute for Infection Biology | And 4 more authors.
BMC Cell Biology | Year: 2010

Background: The nuclear factor-κB (NF-κB) family of transcription factors plays a role in a wide range of cellular processes including the immune response and cellular growth. In addition, deregulation of the NF-κB system has been associated with a number of disease states, including cancer. Therefore, insight into the regulation of NF-κB activation has crucial medical relevance, holding promise for novel drug target discovery. Transcription of NF-κB-induced genes is regulated by differential dynamics of single NF-κB subunits, but only a few methods are currently being applied to study dynamics. In particular, while oscillations of NF-κB activation have been observed in response to the cytokine tumor necrosis factor α (TNFα), little is known about the occurrence of oscillations in response to bacterial infections.Results: To quantitatively assess NF-κB dynamics we generated human and murine monoclonal cell lines that stably express the NF-κB subunit p65 fused to GFP. Furthermore, a high-throughput assay based on automated microscopy coupled to image analysis to quantify p65-nuclear translocation was established. Using this assay, we demonstrate a stimulus- and cell line-specific temporal control of p65 translocation, revealing, for the first time, oscillations of p65 translocation in response to bacterial infection. Oscillations were detected at the single-cell level using real-time microscopy as well as at the population level using high-throughput image analysis. In addition, mathematical modeling of NF-κB dynamics during bacterial infections predicted masking of oscillations on the population level in asynchronous activations, which was experimentally confirmed.Conclusions: Taken together, this simple and cost effective assay constitutes an integrated approach to infer the dynamics of NF-κB kinetics in single cells and cell populations. Using a single system, novel factors modulating NF-κB can be identified and analyzed, providing new possibilities for a wide range of applications from therapeutic discovery and understanding of disease to host-pathogen interactions. © 2010 Bartfeld et al; licensee BioMed Central Ltd.


Bauer C.,Microdiscovery GmbH
Methods in molecular biology (Clifton, N.J.) | Year: 2011

Peak picking is an early key step in MS data analysis. We compare three commonly used approaches to peak picking and discuss their merits by means of statistical analysis. Methods investigated encompass signal-to-noise ratio, continuous wavelet transform, and a correlation-based approach using a Gaussian template. Functionality of the three methods is illustrated and discussed in a practical context using a mass spectral data set created with MALDI-TOF technology. Sensitivity and specificity are investigated using a manually defined reference set of peaks. As an additional criterion, the robustness of the three methods is assessed by a perturbation analysis and illustrated using ROC curves.


Bauer C.,Microdiscovery GmbH | Glintschert A.,Microdiscovery GmbH | Schuchhardt J.,Microdiscovery GmbH
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2014

The increasing size and complexity of high-throughput datasets pose a growing challenge for researchers. Often very different (cross-omics) techniques with individual data analysis pipelines are employed making a unified biomarker discovery strategy and a direct comparison of different experiments difficult and time consuming. Here we present the comprehensive web-based application ProfileDB. The application is designed to integrate data from different high-throughput 'omics' data types (Transcriptomics, Proteomics, Metabolomics) with clinical parameters and prior knowledge on pathways and ontologies. Beyond data storage, ProfileDB provides a set of dedicated tools for study inspection and data visualization. The user can gain insights into a complex experiment with just a few mouse clicks. We will demonstrate the application by presenting typical use cases for the identification of proteomics biomarkers. All presented analyses can be reproduced using the public ProfileDB web server. The ProfileDB application is available by standard browser (Firefox 18 +, Internet Explorer Version 9 +) technology via http://profileDB.-microdiscovery.de/ (login and pass - word: profileDB). The installation contains several public datasets including different cross-'omics' experiments. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2014 Elsevier B.V.


A portable reader module includes a housing, a first receptacle configured to removably receive a portable device having an imager, and a second receptacle configured to removably receive a cartridge. The first receptacle includes a first optical entrance for the imager to the internal space of the housing. The second receptacle includes a second optical entrance to the internal space of the housing. A light-deflecting optical element is arranged within the internal space of the housing to define an optical path between the first optical entrance and the second optical entrance. An illuminating path for illuminating the cartridge is defined in the housing. The housing is configured to allow the internal space to be light-shielded.


A portable reader module includes a housing (100, 101) having an internal space (102), and a first receptacle (110) configured to removably receive a portable device (300) having an imager, wherein the first receptacle (110) includes a first optical entrance (420) for the imager to the internal space (102) of the housing (100, 101). The housing (100, 101) further includes a second receptacle (120) configured to removably receive a cartridge (500), wherein the second receptacle (120) includes a second optical entrance (122) to the internal space (102) of the housing (100, 101) so that the cartridge (500) is visible to and from the internal space (102). A light-deflecting optical element (450) is arranged within the internal space (102) of the housing (100, 101) to define an optical path between the first optical entrance (420) and the second optical entrance (122). An illuminating path for illuminating the cartridge (500) is defined in the housing (100, 101). The housing (100, 101)is configured to allow the internal space (102) to be light-shielded.


A portable reader module includes a housing (100, 101) having an internal space (102), and a first receptacle (110) configured to removably receive a portable device (300) having an imager, wherein the first receptacle (110) includes a first optical entrance (420) for the imager to the internal space (102) of the housing (100, 101). The housing (100, 101) further includes a second receptacle (120) configured to removably receive a cartridge (500), wherein the second receptacle (120) includes a second optical entrance (122) to the internal space (102) of the housing (100, 101) so that the cartridge (500) is visible to and from the internal space (102). A light-deflecting optical element (450) is arranged within the internal space (102) of the housing (100, 101) to define an optical path between the first optical entrance (420) and the second optical entrance (122). An illuminating path for illuminating the cartridge (500) is defined in the housing (100, 101). The housing (100, 101)is configured to allow the internal space (102) to be light-shielded.

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