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Devos D.P.,European Molecular Biology Laboratory | Reynaud E.G.,Science Center
Science | Year: 2010

Bacteria that also have features typical of eukaryotes and archaea may reflect a possible pathway in ancient cellular evolution.

Cunha P.M.,European Molecular Biology Laboratory
PLoS genetics | Year: 2010

Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2) or the zinc-finger transcription factor lame duck (lmd) lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-02-2015 | Award Amount: 6.31M | Year: 2016

Alcohol overuse is an important societal challenge with annual healthcare costs of over 22 billion in Europe. Alcohol is the main cause of liver cirrhosis, which is the 5th and 7th most common cause of life years lost in respectively Eastern and Western Europe. Cirrhosis is considered irreversible but its precursor, liver fibrosis, is reversible when detected before disease progression. GALAXY proposes that crosstalk between the gut microbiome and the liver influences the development and progression of alcoholic liver fibrosis. Here, a dysbiotic microbiome in susceptible individuals leads to progressive liver fibrosis in combination with alcohol overuse. Therefore, interventions aiming to restore a healthy gut microbiome will reduce disease development. We will use state-of-the-art systems medicine tools to improve understanding of the complex interplay present during alcoholic liver fibrosis, to identify at-risk individuals in time and to develop personalised healthcare strategies for alcohol over-users (20% of the EU population >15 years old). GALAXY brings together partners with unique research competences in clinical hepatology, microbiome, multi-omics, biomarkers and bioinformatics. Our aim is to develop novel systems medicine tools which integrate clinical, multi-omics and lifestyle information from alcohol over-users at various stages of the disease and healthy individuals in order to: 1) identify signatures of host-microbial cross-talk during disease development and progression, 2) translate this into biomarkers for diagnosis, stratification and treatment monitoring in alcohol over users, and 3) evaluate new interventions to modulate gut microbiota towards prevention and mitigation of the disease in at-risk individuals. We will also study societal and economic impact of GALAXY biomarkers and treatments to accelerate future development. The GALAXY consortium includes strong SME partners who will enable the results to be exploited commercially.

Agency: Cordis | Branch: H2020 | Program: COFUND-PCP | Phase: ICT-08-2015 | Award Amount: 6.77M | Year: 2016

Over the coming 10-15 years the generation of vast amounts of data created by scientific research domains will create enormous challenges for capturing, managing and processing of this data. Tests have been made but today commercial cloud services do not play a significant role in the production computing environments for the publicly funded research sector in Europe. Stimulated by the Pre-Commercial Procurement (PCP) commitment of leading research organisations from 7 countries, HNSciCloud will pull together commercial cloud service providers, publicly funded e-Infrastructures and the buyers in-house resources to build a hybrid cloud platform on top of which a competitive marketplace of European cloud players can develop their own services for a wider range of users. This project will bring Europes technical development, policy and procurement activities together to remove fragmentation and maximise exploitation. The alignment of commercial and public (regional, national, and European) strategies will increase the rate of innovation. Through a competitive series of design, prototype and pilot steps, HNSciCloud will contract suppliers to deliver a 5% scale deployment of a hybrid cloud platform that can address the extreme needs of world class scientific research, including: Catalog of secure and interoperable services from multiple suppliers that have successfully passed an international recognised certification process Agile procurement process suitable for the dynamic cloud services market and tailored to the needs of the public research sector Development of monitoring frameworks to ensure compliance with international security and interoperability standards, performance criteria and financial benchmarking against global market leaders. The resulting common platform will be evaluated by end-users and exploited as the incubator for new businesses and scientific activities engaging a growing number of buyers, suppliers & users.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SFS-07b-2015 | Award Amount: 9.01M | Year: 2016

This aim of IMAGE is to enhance the use of genetic collections and to upgrade animal gene bank management. IMAGE will better exploit DNA information and develop methodologies, biotechnologies, and bioinformatics for rationalising animal genetic resources. It will demonstrate the benefits brought by gene banks to the development of sustainable livestock systems by: enhancing the usefulness of genetic collections to allow the livestock sector to respond to environment and market changes; using latest DNA technology and reproductive physiology for collecting, storing and distributing biological resources; Minimising genetic accidents such as abnormalities or genetic variability tipping points; Developing synergies between ex-situ and in-situ conservation to maximise resources for the future. To this end, the project will involve stakeholders, SME, and academic partners to achieve the following objectives. At the scientific level, the project will: Assess the diversity available in genetic collections; Search for adaptive traits through landscape genetics in local populations; Contribute to elucidate local populations and major genes history; Identify detrimental variants that can contribute to inbreeding depression; Predict cryobank samples reproductive performance; Facilitate the use of collections for genome-assisted breeding. At the technological level, it will develop: Procedures for harmonising gene bank operations and rationalising collections; Conservation and reproductive biotechnologies; A central information system to connect available data on germplasm and genomic collections. At the applied level, it will develop methods and tools for stakeholders to: Restore genetic diversity in livestock populations; Create or reconstruct breeds fitting new environmental constraints and consumer demands; Facilitate cryobanking for local breeds; Define and track breed-based product brands; Implement access and benefit sharing regulations.

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