ISNI: 0000000122062382 , 0000000122879528
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According to the World Health Organization (WHO), the priority diagnostic needs for human African trypanosomiasis (HAT) are a test for gambiense HAT (gHAT) to identify individuals to receive widened treatment and a test for rhodesiense HAT (rHAT) usable in peripheral health facilities. The ERASE project will develop rapid diagnostic tests (RDT) compliant with the respective WHO target product profiles. For gHAT, current RDTs have inadequate specificity. ERASE will develop a 2nd generation antibody detection gHAT RDT with improved diagnostic performance, incorporating the best selected recombinant antigens. The gHAT RDT performance will be evaluated in 3 clinical trials in epidemiologically different gHAT foci in West- and Central Africa. Manufacturing of the gHAT RDT will be transferred to an African SME (TRL8/9). Diagnosis of rHAT relies on microscopy, resulting in underdetection. For rHAT, ERASE will identify target antigens and develop an antigen capture RDT using the innovative Affimer technology. After evaluation of its clinical performance on biobanked specimens and in a clinical trial, the rHAT RDT will be ready for industrialisation (TRL6). Mapping of health centres, forecasting of RDT consumption and implementation costs, and social research will pave the way for future rHAT RDT introduction. The consortium consists of commercial, non-for profit, academic and governmental partners, including an SME with experience in HAT RDT commercialisation, and will ensure successful RDT development and sustainable production and implementation. Both RDTs will support HAT elimination as targeted by the WHO neglected tropical diseases roadmap. The gHAT RDT will be applicable in a “test & treat” strategy to rapidly stop gHAT transmission. The rHAT RDT will revolutionize rHAT management, allowing faster diagnosis and safer treatment. It will strengthen rHAT surveillance, lead to faster detection of outbreaks and will facilitate elimination of rHAT as a public health problem.
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Reducing agents with neutral organic structures and exceptionally negative redox potentials have received a renewed interest especially since the astonishing advances of their reactivity in organic chemistry. Strong organic electron donors (OEDs) are capable of spontaneous single- or double-electron transfer to organic substrates under mild and homogeneous conditions. The OEDs represent serious rivals to highly aggressive metal-based reducers and emerge as an attractive novel source of reducing electrons. Thus far, they have been scarcely studied and approaches involving OED-promoted electron transfer steps are not sufficiently exploited despite their synthetic potential and their tunability. Consequently, their application scope remains quite narrow. In this context, it is of utmost importance to fully master the chemistry of organic reducers and to establish their fields of application. To address the important shortcomings of their applications, this research proposal aims first at developing novel libraries of organic electron donors able to overcome current boundaries. More importantly, the preparation of air-stable precursors, easily in-situ activated, will extend their practicality. The development of OED-promoted redox catalytic cycles will further fulfill the need for atom-economy and latent approaches, often necessary in the manufacturing industries.Their structures will be diversified and evaluated in order to better understand the factors governing single- or double-electron transfer as well as their reducing power. The diversity of the synthesized donors will thus provide a privileged database to investigate the relationships between molecular structure and reactivity. The second aspect of the project will be dedicated to the exploitation of the OED-generated active species in the reduction of challenging substrates and to the exploration of unprecedented applications. A comprehensive study of their scope and limitations, as well as of the involved mechanism will supply chemists with an exhaustive guide of their capabilities and spread their application panel in radical chemistry. This also falls into a context of searching new reduction methodologies, combining efficiency, modularity and high selectivity, and following the requirement of the sustainable chemistry. Reduction reactions are much less mastered than the oxidative processes extensively used for the fabrication of many everyday objects. With the decline of fossil sources, it is urgent to develop alternative routes to these fundamental compounds. In addition, a special focus will be given to the domain of material chemistry through the use of organic electron donors as initiators of polymerization. We have demonstrated that OEDs represent an unique tool for efficient, simple and room temperature polymerization process, responding to energy-friendly, cost-efficient and secure technical specifications. Their high group tolerance makes them fully compatible with the synthesis of a large range of polymers of wide industrial importance. The additional reducible functional groups accessible with our novel series of organic electron donors will extend the process to the metal-free polymerization of a whole new range of monomers under mild conditions and without the need for co-initiators. To go further with this highly innovative process, a detailed comprehensive mechanistic study will help to i) understand the initiation and chain propagation pathways and ii) prepare optimized OED structures as polymerization initiators. This will illustrate their undeniable potential as efficient and versatile reagents to the scientific and industrial community. In term of social and economic benefits, the financial support of this project will allow us to collect the decisive results necessary to reach the high technology readiness levels required by the European research program Horizon 2020 and access to the pre-industrialization step of our concept.
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Rhizobia are polyphyletic and taxonomically spread among two subclasses of Proteobacteria, the Alpha and the Beta subclasses, and the terms of alpha- and beta-rhizobia have been proposed to distinguish each other. Research has focused for a long time on the alpha-rhizobia, since the beta-rhizobia were recently discovered by Moulin et al. in 2001. The occurence of the nodulation capacity in the beta subclass of Proteobacteria is still anecdotic. Indeed after 100 years of legume samplings and 20 years of genetic characterization of rhizobial diversity, only very few species of beta-rhizobia were found and mostly restrained to Mimosa spp. host legumes. Limited information is available on the efficiency of nodulation and nitrogen fixation in alpha- and beta-rhizobia associated with Mimosa spp. Comparative genomics of alpha- and beta-rhizobia (Amadou et al., 2008; L. Moulin, unpublished) revealed the presence of a set of common nodulation genes in alpha and beta-rhizobia. However few additional common symbiosis-related genes could be found. These results suggest that a unique shared genetic strategy does not explain the specificity of interaction between beta-rhizobia and Mimosa, and that in-silico analyses were not sufficient to identify all symbiosis-related genes. In this project, we propose to study the origin, evolution and specificity of the symbiosis in beta-rhizobia using a dual approach of ecology, including molecular ecology, and functional genomics, to understand: i) the apparition and evolution of nodulation ability in beta-rhizobial populations associated to Mimosa spp., ii) the differences in symbiotic performance of beta-rhizobia and alpha-rhizobia in interaction with Mimosa spp., iii) the specificity of interaction between beta-rhizobia and Mimosa spp., by uncovering the symbiotic genetic bases used by beta-rhizobia compared to alpha-rhizobia (by transcriptomics on Burkholderia, Cupriavidus, and Rhizobium, the three classes of symbiotic populations associated with Mimosa worldwide). Our model plant will be Mimosa pudica, an unique legume model that is able to establish a symbiosis with rhizobia from both Proteobacteria subclasses and thus allows a comparison of i) the diversity of cohabitating populations of alpha and beta-rhizobial symbionts, ii) their specificity and competitiveness towards symbiosis with Mimosa pudica, and iii) two symbiotic genetic programmes and adaptation strategies of nodulation. The scientific program of this project is divided into two tasks corresponding to the two different approaches that will be i) Task 1, a population approach, to describe the taxonomic and genetic diversity of alpha- and beta-rhizobial symbionts populations of Mimosa pudica, to analyse the evolutionary relationships among of their symbiotic genes and establish their symbiotic efficiency and competitiveness, and ii) Task 2, functional genomics that aims at finding the molecular bases involved in the specificity of beta-rhizobia with Mimosa pudica, with a focus on the comparison of genome global expression during M. pudica symbiosis between alpha- and beta-rhizobia. This project should improve our knowledge on the apparition and evolution of nodulation in the beta-subclass of Proteobacteria. Understanding how legume symbiosis evolves is of prime importance for conservation of genetic resources of rhizobia and their selection for ecological and agronomical purposes. As Burkholderia and Cupriavidus species are also known to host many human and plant pathogens, describing infection processes in these genera should identify if these symbiotic species share features with taxonomically close pathogens (as Burkholderia mallei or cepacia), with high relevance in terms of sanitary questions if they had to be used for inoculums. Symbiosis in beta-rhizobia may also use alternative signal molecules with potential in biotechnology.
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IRD is a French public research Institution operating under the joint authority of the French Ministry for Higher Education, Research and Innovation and the French Ministry for Europe and Foreign Affairs. It takes an original approach to research, expertise, training and knowledge-sharing for the benefit of countries and regions, making science and innovation key drivers in their development. Scientific progress is necessary to further sustainable and human development: IRD carries this conviction with it wherever it is present, and wherever it works with its partners. IRD is a key French player on the international development agenda. Its work is founded on an original model: equitable scientific partnership with developing countries, primarily those in the intertropical regions and the Mediterranean area.IRD sets its priorities in line with the Sustainable Development Goals (SDGs) adopted by the United Nations in September 2015, to steer development policies. Combining critical analysis into the implementation of these goals, IRD seeks to tackle the challenges facing us today: global, environmental, economic, social and cultural changes that affect the whole planet. IRD also fulfills missions of expertise, training and dissemination of scientific and technical information in France and in its partner countries. As part of this last mission, the IRD implements actions to disseminate scientific and technical culture in order to strengthen the dialogue between scientists and civil society, especially towards young people. Each year, nearly 400 public meetings are organized - on an international scale. → This document lists the actions carried out by IRD to build the "scientific communication and culture" component of the PRC and JCJC projects of the 2018 and 2019 generic calls for projects. Three mediation actions will thus be carried out: 1. F[r]iction podcasts « When science meets fiction! » 2. Forum theater "I acclimate therefore I am". 3. Films about malaria
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