Instituto Superiore Of Sanita
Instituto Superiore Of Sanita
Instituto Superiore Of Sanita | Date: 2016-12-21
Activation of HIV-1 replication causes oxidative stress, which in turn potentiates HIV-1 replication. The common basis for the compounds of the present invention is: A) the capacity of reactivating HIV-1 from latency, and B) the ability to counteract the cellular machinery which activates in order to limit the effects of oxidative stress. In this way, oxidative stress can be potentiated and a chain reaction is sparked. This chain reaction induces a more efficient reactivation of HIV-1 from latency and, in some cases, induces selective killing of the infected cells. Actions A) and B) can either be carried out by one drug exerting both effects, or obtained by the combined use of distinct drugs. There are two main cellular machineries counteracting oxidative stress, i.e. the thioredoxin (Trx) thioredoxin reductase (TrxR) system and glutathione. Herein, we present drug strategies capable of exerting action B) by blocking either of the two machineries.
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: IA | Phase: WATER-1b-2015 | Award Amount: 8.77M | Year: 2016
INTCATCH will instigate a paradigm shift in the monitoring and management of surface water quality that is fit for global waters in the period 2020-2050. INTCATCH will do this by developing efficient, user-friendly water monitoring strategies and systems based on innovative technologies that will provide real time data for important parameters, moving towards SMART Rivers. The business model will transform water governance by facilitating sustainable water quality management by community groups and NGOs using a clouds data linked to a decision support system and eco-innovative technologies. The INTCATCH project will use demonstration activities to showcase eco-innovative autonomous and radio controlled boats, sensors, DNA test kits and run-off treatment technologies. Actions which develop and evaluate these in a range of catchments will address the important innovation barriers to uptake, notably, a lack of knowledge of new technologies and their capabilities, identified by the European Innovation Plan (EIP) on water. By conceptually moving the laboratory to the field, the monitoring techniques that will be developed aim to supersede the inefficient, time dependent, costly and labour-intensive routine sampling and analysis procedures currently deployed to understand the quality of receiving waters. It will compliment routine monitoring that is required for baseline datasets, but also enable cost-effective impact and management investigations. INTCATCH will incentivise stakeholder innovation in monitoring and will facilitate new financing for innovation through its innovative franchise business model and empowerment of community groups and NGOs. The market ambition is that the INTCATCH business will facilitate an eco-innovative approach to deliver good quality water bodies across Europe and beyond. This will support green growth, increase resilience to climate change and capture greater market-share for Europes innovative industries.
Agency: European Commission | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016
Understanding the human brain is one of the greatest scientific challenges of our time. Such an understanding can provide profound insights into our humanity, leading to fundamentally new computing technologies, and transforming the diagnosis and treatment of brain disorders. Modern ICT brings this prospect within reach. The HBP Flagship Initiative (HBP) thus proposes a unique strategy that uses ICT to integrate neuroscience data from around the world, to develop a unified multi-level understanding of the brain and diseases, and ultimately to emulate its computational capabilities. The goal is to catalyze a global collaborative effort. During the HBPs first Specific Grant Agreement (SGA1), the HBP Core Project will outline the basis for building and operating a tightly integrated Research Infrastructure, providing HBP researchers and the scientific Community with unique resources and capabilities. Partnering Projects will enable independent research groups to expand the capabilities of the HBP Platforms, in order to use them to address otherwise intractable problems in neuroscience, computing and medicine in the future. In addition, collaborations with other national, European and international initiatives will create synergies, maximizing returns on research investment. SGA1 covers the detailed steps that will be taken to move the HBP closer to achieving its ambitious Flagship Objectives.
Agency: European Commission | Branch: H2020 | Program: COFUND-EJP | Phase: SC1-PM-05-2016 | Award Amount: 74.06M | Year: 2017
The overarching goal of the European Human Biomonitoring Initiative (HBM4EU) is to generate knowledge to inform the safe management of chemicals and so protect human health. We will use human biomonitoring to understand human exposure to chemicals and resulting health impacts and will communicate with policy makers to ensure that our results are exploited in the design of new chemicals policies and the evaluation of existing measures. Key objectives include: Harmonizing procedures for human biomonitoring across 26 countries, to provide policy makers with comparable data on human internal exposure to chemicals and mixtures of chemicals at EU level; Linking data on internal exposure to chemicals to aggregate external exposure and identifying exposure pathways and upstream sources. Information on exposure pathways is critical to the design of targeted policy measures to reduce exposure; Generating scientific evidence on the causal links between human exposure to chemicals and negative health outcomes; and Adapting chemical risk assessment methodologies to use human biomonitoring data and account for the contribution of multiple external exposure pathways to the total chemical body burden. We will achieve these objectives by harmonizing human biomonitoring initiatives in 26 countries, drawing on existing expertise and building new capacities. By establishing National Hubs in each country to coordinate activities, we will create a robust Human Biomonitoring Platform at European level. This initiative contributes directly to the improvement of health and well-being for all age groups, by investigating how exposure to chemicals affects the health of different groups, such as children, pregnant women, foetuses and workers. We will also investigate how factor such as behavior, lifestyle and socio-economic status influence internal exposure to chemicals across the EU population. This knowledge will support policy action to reduce chemical exposure and protect health.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-04-2015 | Award Amount: 6.00M | Year: 2016
The BlueHealth Consortium brings together a multi-disciplinary team of experts reaching across all 28 European Union countries. The proposed 4.5 year BlueHealth Project takes an international, interdisciplinary and multi-sector approach to health promotion and disease prevention by investigating the relationship between the EUs blue infrastructure and the health and well-being of its citizens. Blue infrastructure refers to the network of natural and man-made aquatic environments providing a range of multi-sectorial services (e.g. transportation, fresh water provision). There has been no systematic attempt to detail the potential impacts of our blue infrastructure on health promotion and disease prevention, nor to develop guidelines on how health should be considered when developing blue infrastructure interventions, particularly across sectors. BlueHealth will address this gap. The majority of Europeans live in cities built on inland waterways, lakes, or the coasts. BlueHealth will focus on urban blue infrastructures. The EUs blue infrastructure offers significant health and well-being related opportunities and benefits (eg urban cooling, recreation), but also challenges and stressors (eg flooding, microbial/chemical pollution). BlueHealth will investigate these trade-offs, with the aims of quantifying the impacts on population health and well-being of interventions and policy initiatives connected to blue infrastructure, and identifying success factors and obstacles of inter-sectorial collaborations. Assessments of health and environment benefits, risks and costs will improve our understanding of the role of urban blue infrastructures on across-sector health promotion and disease prevention. The Partners have collaborations across the Environment, Health, and Climate sectors, and extensive experience with inter-institutional, multi-sectorial, interdisciplinary research programmes employing innovation, stakeholder engagement, dissemination, and policy impact.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-09-2015 | Award Amount: 28.14M | Year: 2016
Many HIV vaccine concepts and several efficacy trials have been conducted in the prophylactic and therapeutic fields with limited success. There is an urgent need to develop better vaccines and tools predictive of immunogenicity and of correlates of protection at early stage of vaccine development to mitigate the risks of failure. To address these complex and challenging scientific issues, the European HIV Vaccine Alliance (EHVA) program will develop a Multidisciplinary Vaccine Platform (MVP) in the fields of prophylactic and therapeutic HIV vaccines. The Specific Objectives of the MVP are to build up: 1.Discovery Platform with the goal of generating novel vaccine candidates inducing potent neutralizing and non-neutralizing antibody responses and T-cell responses, 2. Immune Profiling Platform with the goal of ranking novel and existing (benchmark) vaccine candidates on the basis of the immune profile, 3. Data Management/Integration/Down-Selection Platform, with the goal of providing statistical tools for the analysis and interpretation of complex data and algorithms for the efficient selection of vaccines, and 4. Clinical Trials Platform with the goal of accelerating the clinical development of novel vaccines and the early prediction of vaccine failure. EHVA project has developed a global and innovative strategy which includes: a) the multidisciplinary expertise involving immunologists, virologists, structural biology experts, statisticians and computational scientists and clinicians; b) the most innovative technologies to profile immune response and virus reservoir; c) the access to large cohort studies bringing together top European clinical scientists/centres in the fields of prophylactic and therapeutic vaccines, d) the access to a panel of experimental HIV vaccines under clinical development that will be used as benchmark, and e) the liaison to a number of African leading scientists/programs which will foster the testing of future EHVA vaccines through EDCTP
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-02-2015 | Award Amount: 5.99M | Year: 2016
The goal of this multidisciplinary project is to comprehensively characterise high-grade serous ovarian cancer (HGS-OvCa) at single-cell level, identify the best combination of drug combination to kill HGS-OvCa populations and commercialise a predictive biomarker kit for finding the right therapeutic regimen to the right patient. This project takes an advantage on prospectively and longitudinally collected fresh sample specimens from multiple anatomic sites of HGS-OvCa patients with metastatic disease. Fluorescence activated cell sorting and recently developed mass cytometry are used to identify subpopulations in HGS-OvCa tumors. This is followed by single-cell analysis at genetic and transcriptomics levels, and ex vivo drug screening experiments. These data will be used to establish network models to predict the most effective combinatorial treatments. The key results will be validated with existing HGS-OvCa data together with prospective and retrospective cohorts and in vivo models. The clinically most actionable treatment suggestions from our modelling efforts will be translated to HGS-OvCa patient care. Ovarian cancer kills more than 40,000 women in Europe every year due to lack of effective and long-lasting therapeutic regimens. HERCULES presents an innovative strategy to suggest effective treatments that lead to a marked decrease in ovarian cancer deaths and reduce the number of expensive but inefficient treatments. Our approach paves the way to move beyond the current trial-and-error clinical assessment of drug combinations toward more systematic prediction of the most effective drug combinations for each patient. The proposed approach will be a major breakthrough in systems medicine and will benefit individual ovarian cancer patients and the health-care system through more effective treatments, and the diagnostic and pharmaceutical industry through tools for better stratified clinical trials, and novel treatment and diagnostic modalities.