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Among the greatest challenges of the 21st century are bacterial diseases that permanently threat plants and animals, including humans to whom they often are lethal. In plant and animal production, bacteria can cause severe yield reductions if not effectively controlled. However, the current control measures include use of environmentally problematic antibiotics, which in addition may lead to appearance of bacterial strains resistant to these antibiotics. Recent progress in the host laboratory using a Genome Wide Association Study (GWAS) of wheat reveals a hitherto unknown recognition mechanism of the effector translocator widely conserved in pathogenic bacteria. The associated receptor complex is predicted to have wide potential for exploitation in bacterial disease control, not only in crop plants but also in livestock production. In the T-REX project, number of parallel efforts will be taken to characterize the recognized T3SS component, the membrane bound receptor complex and the activated immunity. This will be undertaken using an integrated approach, which involves my background knowledge and experiences combined with the ones of the host institution within molecular genetics, biochemistry, molecular biology and bioinformatics. This study will shed light on the role of T3SS as a PAMP, which will help us to elucidate the complex plant-bacterial interactions and can potentially lead to the development of new phyto-pathogen control strategies. T3SS being conserved among plant and animal pathogen, the outcome of the T-REX project has potential for extrapolation into animal pathological systems, including humans, and may contribute to the world of medicine.

Mitochondria participate during the metabolic reprogramming of naive T cells. However, the molecular mechanisms by which mitochondria regulate T cell differentiation remain elusive. The project aims at revealing the mechanisms behind mitochondrial function and lineage specification and maintenance. Combining high-throughput analysis of gene expression and chromatin epigenetic status with biochemical, metabolic, cellular, and in vivo and in vitro approaches, we want to assess how mitochondria coordinate the metabolic status of the cell to transcriptional and epigenetic changes to control T cell differentiation and function in distinct inflammatory environments. For that our challenges are; (Obj.1) To investigate the role of mitochondrial dynamics in the metabolic reprogramming of T cell differentiation, (Obj.2) To study how metabolic pathways shape the transcriptional and epigenetic networks of the T cell lineages, (Obj.3) To identify mitochondria-to-nucleus signaling pathways that regulate T cell differentiation through modification of the transcriptional and epigenetic landscape, and (Obj.4) To investigate the therapeutic potential of reprogramming mitochondrial function in T cell responses against infection and cancer. REPROGRAMMIT will unveil significant breakthrough on (1) how mitochondria regulate the metabolic profiles of the distinct T cell subsets, (2) the identification of molecular candidates that reverse or modify T cell transcriptional programs through regulation of mitochondrial function, (3) the understanding on how nutrient availability and metabolic intermediates shape T cell differentiation and plasticity. In sum, REPROGRAMIT puts forward an ambitious and multidisciplinary but feasible program with the wide purpose of identifying novel checkpoints based on the crosstalk between mitochondria and the epigenome, with the final goal to modulate T cell immune responses against infection and cancer by reprogramming mitochondrial function.

An eco- industrial park is an area where businesses work together to optimize the use of resources. Waste from one company provides the raw material or energy for another. This synergy between industries fosters economic benefits while contributing to sustainable development. The main purpose of the project Recycling Business Models – RBM is indeed to investigate and analyse the possibility to transform traditional science and technology parks in more sustainable areas, to establish the basis of models of Eco science and technology parks. The principal objective of the project is indeed to create a methodology and a specific strategy to impulse especially the creation of new business opportunities for SMEs and the creation of new companies, based on the revalorisation of the wastes, equipment and its reincorporation in the life cycle of the companies located in science and technology parks. More than 80% of the companies located within technology park in Europe are SMEs, which create the majority of new jobs in the economy of these countries. The development and improvement of ecosystem of innovation support to SMEs is indeed crucial for the scale up of the companies and the creation of new jobs, including the recruiting of talent. RBM is based specifically on the opportunities for SMEs and companies the Circular Economy (CE) perspective can bring. New business models within this concept are beginning to deliver success and impact in terms of driving competitive benefits. Creating enterprises around sustainable models can improve both their environmental impact and competitiveness. Great opportunities are arising due to new consumer demands, environmental regulatory pressures and innovation challenges, and early SMEs adopters are likely to enter the market and attract investment so the project will investigate on the establishment of new strategies for the design and delivery of more adequate innovation support programmes for SMEs within the field of CE.

Core body temperature is among the best-guarded constants in homeothermic species. It results from the evolution of physiological mechanisms capable of regulating the production as well as the exchange of heat with the environment. The objective of my proposal is to define a new role for the liver in adaptive thermogenesis whereby the liver will be involved in heat production under the regulation of the hepatic sympathetic nerve. I will first ascertain that the liver can generate extra heat when adaptive thermogenesis is triggered (Aim 1). Hepatic adaptive thermogenesis will be demonstrated using a combination of interdisciplinary, cutting-edge technologies normally applied to the fields of physics and chemistry. I will then determine the molecular foundation of this hepatic heat production (Aim 2). For this purpose, OMICs data (transcriptomic, proteomic and metabolomics) will be generated from cold-exposed liver tissues in order to identify: (1) the hepatic molecular heating mechanism; (2) the expected metabolic rewiring necessary to sustain prolonged heat production from thermogenic hepatocytes. Finally, I will study how hepatic adaptive thermogenesis is regulated by the hepatic sympathetic nerve at the anatomical level and by the adrenergic receptor Adrb3 at the molecular level (Aim 3). For this purpose, I will use a combination of surgical (hepatic sympathectomy) and genetic (generation of liver-specific beta-adrenergic receptor 3 knockout mice) ablation techniques. Longstanding observations, together with my own preliminary results argue for this existence of hepatic adaptive thermogenesis and its molecular characterization would certainly represent a major breakthrough for both our fundamental understanding of homoeothermic physiology as well as for future clinical applications. Demonstrating that the liver is involved in adaptive thermogenesis would certainly open new avenues for the treatment of nonalcoholic fatty liver disease, a major disease in Europe.

Neurodevelopmental disorders affect millions of children in Europe and worldwide. A large body of literature indicates that inhibitory GABAergic transmission thorough Cl-permeable GABAA receptors is defective in many of these disorders. However, effective pharmaceutical treatments are still needed. There is increasing scientific evidence that varying the intracellular Cl concentration is one of the more physiological and effective ways to modulate GABAAergic transmission. This concentration is mainly established by the Cl importer NKCC1 and the Cl exporter KCC2. Importantly, the NKCC1/KCC2 ratio is defective in several brain disorders. Moreover, NKCC1 inhibition by the FDA-approved diuretic bumetanide rescues many symptoms in animal models. These findings have already led to clinical studies of bumetanide to treat a broad range of brain disorders. However, this requires chronic treatment, which poses serious issues for drug compliance, given the diuretic effect of bumetanide caused by the inhibition of the kidney-specific Cl transporter NKCC2. Crucially, these issues could be solved by selective NKCC1 inhibitors, which would have no diuretic effect. Yet there is still very little knowledge of the structure-function relationship of NKCC1 in terms of ion transportation and how bumetanide acts on NKCC1. The main goal of this fellowship is to resolve NKCC1’s structure using X-Ray crystallography and/or cryo-electron microscopy. This effort will be coupled to the functional characterization of NKCC1 using in vitro and in silico approaches. The fellow will thus integrate her research skills with key expertise in the structural and molecular biology of ion transporters, allowing her to grow into an independent group leader. Ultimately, this project will provide unprecedented insights into the structure-function relationships of NKCC1 in terms of ion transportation. This will critically accelerate the discovery of new and urgently needed drugs for brain disorders.

Understanding Earth’s climate system is a major aim of the H2020 work programme. The chemical weathering of silicate and carbonate minerals is a key component of Earth’s climate system by exchanging large volumes of carbon between atmospheric and geologic reservoirs. Commonly, weathering models focus on the steady production, chemical alteration, and erosion of regolith and soil. However, the majority of fresh, weatherable sediment on Earth’s surface is produced in active mountain ranges where unsteady bedrock landsliding is the dominant erosion process. There, existing weathering models do not apply. The lack of data and models for chemical weathering in bedrock landslide deposits presents a major knowledge gap that limits our predictions of weathering dynamics and, ultimately, our understanding of Earth’s climate system. The goal of WetSlide is to quantify the impact of landslide erosion on chemical weathering fluxes from mountain ranges with three research objectives: 1) Assess millennial-scale variations of weathering rates in landslide deposits with a unique dataset of landslide-seepage-water chemistry from New Zealand; 2) Quantify erosion timescales of landslide deposits by measuring and compiling deposit volumes of dated landslides; 3) Develop and calibrate a model for weathering in landslides based on data from 1-2. This model will be combined with a regolith weathering model to estimate landscape-scale weathering fluxes. By providing the first quantitative study of weathering in landslide deposits, WetSlide has the potential to re-define the impact of mountain belt uplift on the inorganic carbon cycle and to drive a step-change in the understanding of global chemical weathering dynamics. Moreover, interdisciplinary training by experts at two world-leading research institutions will shape a competitive young researcher with a rare combination of skills who can effectively contribute to EU research excellence in integrative natural sciences.

Energy is crucial for the developing World and must be provided when needed to avoid serious impact on society. Among all energy forms, electricity has an increasingly central role. Electricity security is the power system's capability to withstand disturbances or contingencies with an acceptable service disruption and represents a crucial concern for policy decision making at all levels. Usually, service disruption is due to cables insulation damage, often caused by or accompanied by partial discharge (PD) event that is a localized electrical discharge that partially bridges the insulation between conductors. Since PD is one of the best early-warning indicators of insulation damage, the on-line PD location is the most suitable method to monitor network integrity and a desirable network protection method to guarantee electricity security. The project’s main objective is to develop a new method for on-line PD location based on the innovative electromagnetic time reversal (EMTR) theory. It focuses on three specific objectives:To develop a numerical test bench to study PD on networks, through a training on computational electromagnetics (CEM).To design the new method, studying EMTR theory through a secondment under the supervision of the theoretician of EMTR theory for electromagnetic compatibility (EMC) field application. To experimentally validate the method, through a secondment at the industrial partner, expert in on-line PD condition monitoring. The project, characterized by strong interdisciplinarity and mobility in a European context, will widen the fellow skills with new experience giving her the possibility to reach an independent position of research leadership. She has significant experience in the EMC field that will be enhanced studying CEM techniques and EMTR theory, both at theoretical level, working with the high-level researchers’ staff of Host Institution and Academic partner, and at experimental level through the secondment at the industrial partner

The aim of the MONET project (Merkel cell polyomavirus Oncogenic Network) is to provide a state-of-the-art understanding of Merkel cell carcinoma (MCC) tumorigenesis. Viral pathogens are estimated to be responsible of ~12% of cancers worldwide and represent useful models for the study of oncogenesis mechanisms. Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer detected in ~2500 patients per year in Europe and has recently been linked with a clonal integration of the Merkel Cell polyomavirus (MCPyV) in more than 80% of cases. MCPyV is a 6-protein encoding system, expressing only two proteins with reported oncogenic functions. This limited proteome size thus allows system-wide study of its associated oncogenic mechanisms. This multi-pronged project consists of: (i) identifying the critical interactions of viral and host proteins in MCC oncogenesis; and (ii), using NOD scid mice cell line derived xenografts (CDXs), validate MCPyV host-proteins drug targeting strategies to combat MCC tumorigenesis. Using cutting-edge mass spectrometry-based techniques combined with CRISPR interference approaches in relevant human cancer cell systems, these studies will uncover new protein-protein interactions essential for tumorigenesis. MCPyV+ MCC CDXs will be used to establish the functional relevance of novel virus-host protein interactions and to assess the therapeutic potential of targeting these host interactors as anti-cancer strategies. The application of these proteomic and functional approaches will allow for a better understanding of MCPyV-associated carcinogenesis. In a broader view, it will define a new framework for identifying druggable targets in pathogen-driven cancers. This project will underpin future translational researches, and hence appears as a fundamental step for therapeutic development.

Lightyear, an international team of 90 engineers including triple winners of the World Solar Challenge, experienced engineers (180+ years) from the aerospace, racing and automotive industry (e.g. ASML, Tesla, Ferrari and Inalfa) and alumni of the Eindhoven University of Technology, develops the first commercially available electric solar car in the world that charges itself: the Lightyear One. The extremely efficient family car will be able to drive for weeks or even months on self-generated solar energy. The engineers started from the rationale that the car should be incredibly efficient, in order to make an independent entity having its own energy source. To achieve this, Lightyear had to minimize the car’s energy consumption and maximize its energy input, by using four inwheel motors instead of one rigid motor, lowering the total mass of the car by using lightweight biobased materials, redesign to improve aerodynamics, developing a new battery pack; integrating their in-house custom developed solar panels on the roof and the bonnet of the car. Result: a car that excellences in driving range, in weight, in energy consumption, sustainability and operation costs compared to market's-state-of-the-art. Range anxiety, dependency on energy (charging) infrastructure and the use of non-renewable/inefficient energy sources to charge your car will belong to the past. In this project, Lightyear aims to develop, validate and demonstrate the first Lightyear One and associated assembly line, bringing their innovation from TRL 5/6 to 8. Lightyear expects to produce the first 10 signature cars in 2020, and start serial production from 2021 onwards. EBITDA is expected to turn positive in 2021 with a fivefold increase of FTEs. This development reinforces competitiveness and performance of European transport manufacturing industries on the global market.