Plasmodium vivax infection, the main cause of malaria in Latin America and Asia, affects 14.3 million people annually, with 3.3 billion people at risk worldwide. Individuals are repeatedly infected due to relapses from dormant liver forms or reinfection, with a major impact on wellbeing and socioeconomic development. No effective vaccine is available. P. vivax entry into red blood cells (RBCs) requires sequential ligand-receptor interactions and parasites can only invade immature RBCs (reticulocytes) expressing high levels of CD71, which account for up to 1.5% of circulating RBCs. CD71 is the receptor for PvRBP2b, a member of the P. vivax reticulocyte-binding protein (PvRBP) family. Another key pathway involves the Duffy-binding protein (PvDBP) and its receptor on RBCs, the Duffy antigen (DARC). RBCs lacking DARC are common among African descents and are refractory to P. vivax infection. The CD98 heavy chain (CD98hc) was recently identified as a reticulocyte-specific receptor for another PvRBP family member, PvRBP2a. Encoded by the SLC3A2 gene, CD98hc is part of a widely expressed multifunctional complex involved in amino acid transport, cell adhesion, immune activation, and murine erythropoiesis. We hypothesize that CD98hc might be a key modulator of human erythropoiesis and vivax malaria risk. Naturally occurring polymorphisms at the SLC3A2 locus that affect CD98hc expression or function might inhibit blood-stage P. vivax infection in two ways: (1) by accelerating human reticulocyte maturation, reducing CD71 expression and therefore inhibiting parasite entry via the CD71-PvRBP2b pathway and (2) by decreasing PvRBP2a binding affinity to its host-cell receptor, therefore partially blocking parasite entry via the alternative CD98hc-PvRBP2a pathway. This project aims at further exploring in vivo the dual role of CD98hc in human erythropoiesis and P. vivax infection. We will exploit unique humanized mice that support both human erythropoiesis and blood-stage P. vivax infection, with a focus on the bone marrow (the primary erythropoietic organ and extravascular reservoir of P. vivax). We will also characterize SLC3A2 polymorphism and anti-PvRBP2a antibody responses in a cohort of Amazonians with varying susceptibility to P. vivax infection. We will examine: (1) the role of CD98 in human erythropoiesis and P. vivax infection, (2) whether genetic diversity at the SLC3A2 locus and levels of anti-PvRBP2a antibodies in Amazonians are associated with their vivax malaria risk, and (3) the effects of CD98hc-targeted interventions in vivo on erythropoiesis and P. vivax infection. Our proposal is an international multidisciplinary effort that deploys several complementary expertise and resources, namely a unique in vivo humanized model of human erythropoiesis and P. vivax infection (French coordinator S. Garcia), field epidemiology and cohorts of P. vivax-exposed individuals in the Amazon (Brazilian coordinator M. U. Ferreira), genetics and invasion biology of malaria parasites (Brazilian Partner D. Y. Bargieri) and molecular immunology, malaria vaccines, and recombinant monoclonal antibody production (Brazilian Partner S. B. Boscardin). This project will generate new insights into P. vivax interactions with a key host-cell receptor, opening new opportunities to devise new therapeutics using anti-CD98hc strategies and anti-PvRBP2a-based vaccines.

Communication networks of interconnected devices lie at the core of many key future technologies such as distributed control systems for autonomous vehicles, sensor networks for structural health monitoring and for smart cities. In addition to reliability, all these applications come with strict requirements in terms of: energy efficiency, security, latency and self-optimization capabilities, and demand for innovative enabling technologies. The emerging Internet of Things (IoT) paradigm, projected to connect billions of wireless "things" (wireless sensors, wearables, biochip transponders, etc.) in a vast network with drastically different characteristics among its components, has moved from being a futuristic vision to an increasing reality over the recent years. The ELIOT project is perfectly timed to address the main challenges above. Specifically, we will focus on the following key objectives to IoT applications: 1) Energy efficient transceiver design and allocation policies: development of advanced low-energy transmit and receive techniques, including channel estimation for transceivers with coarse quantization (1-3 bits), and to exploit energy harvesting capabilities to mitigate interference and increase the device's lifespan; 2) Long-term security solutions: design of novel cross-layer security protocols based on software defined networking and physical layer security, avoiding the incremental application of existing security technologies; 3) Distributed learning, detection and resource allocation/management: development of new distributed and efficient algorithms tailored to the IoT environment and underlying network infrastructure that take into account the device mobility, their limited energy and computational power; 4) Improving the energy efficiency vs. latency tradeoff by channel coding: short-length error-correction coding schemes together with their derivatives and decoding algorithms will be designed for low-energy and low-latency IoT applications. Tackling these objectives will require a wide interdisciplinary palette of expertise ranging from signal processing, wireless communications, information theory and coding, security and cryptography, distributed and online optimization, game theory and learning. The diverse and complementary expertise of the project's team places ELIOT in an ideal position to decisively contribute to the expansion of future generations of IoT ecosystems.

Advances in sequencing techniques and genome assembly pipelines have allowed the development of large-scale projects focused on generating high-quality reference genomes that will contribute to a better understanding of species diversity and evolution. The establishment of reference genomic resources is also key to biodiversity conservation issues. Data from these and other initiatives have allowed pangenome-wide studies, enabling researchers to move from individual-level to species-level analysis of genomic diversity, as well as in identifying key genes implicated in the adaptation to contrasting environments. Results from such research have redefined the importance of wild species in the search for adaptive traits to climate adaptation, since some genes that could be a target for selection are simply not present in cultivated species. In addition, new innovative research is looking at the use of comparative analysis and pangenomes towards understanding species’ evolution and adaptation. Coffee is mainly produced by two species of the genus Coffea: C. arabica and C. canephora. They are sensitive to climatic variations and a loss of 50% of cultivable areas is expected by 2050 with considerable socio-economic impacts for the 100 million people worldwide depending on this production. However, alternatives exist via wild coffee tree species that are better adapted to contrasting climates and could replace cultivated species or be used in breeding programs via interspecific hybridization. Nevertheless, the diversity of wild Coffea species remains poorly known at the genetic and genomic levels and the factors related to their adaptation to contrasting climates are poorly studied. Our current knowledge is insufficient to obtain a complete understanding of the evolution of genome structure, structural variations and genes of interest in coffee trees due to the lack of genomic resources. The goal of our project is to begin tackling this situation by taking advantage of the development of new sequencing technologies, and state-of-the-art bioinformatics tools for genome assembly, comparative genomics, and pangenome integration. The diversity of wild species conserved in ex-situ collections, phenotypic resources and environmental information are available. Our main goals are to obtain via an interdisciplinary approach: (i) highly contiguous, accurate, and annotated reference genome assemblies and transcriptomes of 33 wild Coffea species, representing the diversity of the genus based on the phylogenetic relationships we established; (ii) A complete view of structural genome evolution in the genus Coffea with the integration of genomic elements such as large structural variations and transposable element over an evolutionary time step of 15 My; (iii) A detailed evolutionary history of biosynthetic pathways and clusters, like the caffeine biosynthetic pathway; (iv) An assembly of a genus-level super-pangenome integrating the core and dispensable genomes and the relationships between the dispensable genome and factors involved in environmental adaptation; and finally (v) integrating the research outputs into a visualization system allowing to browse annotations, gene families, orthologous and paralogous relationships, collinearity of loci of interest and display pangenomes. The results of our project will have major implications on the knowledge of the evolution of the structural features of a tropical tree genus, the evolutionary pattern of biosynthesis pathways and on the association between the function of the genes of the “shell” and “cloud” genomes and their implication in the adaptation to environmental constraints. Our long-term ambition is to provide open resources and collaborative platforms to promote the use of wild species in future crop improvement schemes and to promote their protection and conservation species in their natural environment and in ex situ collections.