Plant diseases are among the most important problems in agriculture and the use of disease resistance (R) genes is a key strategy for plant protection. ImmuneReceptor addresses fundamental questions in plant immunity to generate transferable knowledge for sustainable crop protection. It focuses on the most important class of disease resistance proteins, termed NLRs that are characterized by nucleotide-binding and leucine-rich repeat domains. NLR-coding genes are the main class of R genes employed in resistance breeding and their innovative, knowledge-based use (e.g. in pyramiding or variety mixture strategies) is a central element in sustainable crop protection. NLR proteins act as immune receptors and recognize pathogen-secreted virulence factors (effectors) termed avirulence proteins (Avrs). They are further subdivided according to their N-terminal signalling domain: CNLs, the only class of NLRs present in cereals, harbour a coiled-coil (CC) domain and TNLs possess a Toll-Interleukin-1 (TIR) domain. Despite intense research on plant NLRs over the last 20 years, many aspects of their activity are still unknown. In particular, the molecular details of Avr recognition and the link between Avr recognition and resistance activation are poorly defined. In ImmuneReceptor, rice CNLs and their matching Avr proteins from the rice blast fungus Magnaporthe oryzae as well as selected CNLs from other cereals will be investigated by a combination of cutting edge structural biology, protein biochemistry, molecular genetics and phytopathology approaches to get a detailed structural and mechanistic understanding of Avr protein recognition and CNL function. For this, we will rely on our previous work that established the CNL pair RGA4/RGA5 from rice as a model for cereal CNLs. Both RGA4 and RGA5 were shown to be required for the recognition of AVR1-CO39 and AVR-Pia, two sequence-unrelated M. oryzae effectors. RGA5 interacts physically with either effector via a C-terminal non-LRR sensor domain of ~200 amino acids (RGA5C-ter) and this direct binding is required for resistance and confers specificity. RGA4 is a constitutively active cell death inducer that is repressed by RGA5. Upon effector binding, RGA5 loses its repressor activity and RGA4 triggers resistance and cell death. In the ImmuneReceptor project, molecular details of Avr-RGA5 binding will be elucidated by resolving the three-dimensional structure of RGA5C-ter and of complexes between RGA5C-ter and AVR1-CO39 or AVR-Pia. In vitro and in vivo mutant analysis will be performed to validate these structural models of Avr recognition and to investigate structure-function relations. In addition, structure guided design of new recognition specificities will be performed to serve as a first proof of concept for this type of approach on plant NLRs. In addition, the molecular bases of RGA4-RGA5 interaction will be investigated. RGA4 and RGA5 form homo and hetero-complexes and the composition and stoichiometry of these complexes in the resting and the activated state will be determined. The CC domains are the best candidates to mediate RGA4-RGA5 complex formation since they form homo and hetero-interactions. The molecular bases of these interactions will be addressed by determining the three-dimensional structures of RGA4 and RGA5 CC domains and of their hetero complexes. These structural models will be validated by in vitro and in vivo mutant analysis to confirm the amino acids that mediate CC interactions and to determine the role of homo and hetero CC interactions in resistance activation and repression. Detailed knowledge on RGA4/RGA5 will be extended to CNL heteropairs homologous to RGA4/RGA5 in rice and other important cereals. By a combination of structural biology and functional approaches it will be determined to what extend the mechanisms governing RGA4/RGA5 function are generic to this entire group of cereal CNL pairs and how specificity in their interactions is generated.

Non-coding pervasive transcription initiating from cryptic signals or resulting from terminator read-through is widespread in all organisms. Its biological role is well-established in eukaryotes, but poorly understood in bacteria. Two major mechanisms control bacterial pervasive transcription: transcription termination by Rho and RNA degradation by RNases. Our recent data suggest a connection between these two pathways. The multidisciplinary project CoNoCo aims to define the mutual contributions of Rho and RNase III in the control of pervasive transcription in the Gram-positive model bacteria Bacillus subtilis and Staphyloccoccus aureus. It will also establish the roles of the non-coding transcriptome in bacterial cell biology highlighted by recent discoveries of Rho-mediated regulation of B. subtilis cell differentiation and the involvement of the double-strand specific RNase III in gene regulation by small non-coding RNAs.

The project “COmmunication MEdiation TransfEr of Sciences in Champagne Ardenne ” (COMETES-CA) is supported by the University of Reims Champagne-Ardenne (URCA) in close synergy with the Center for Technical and Industrial Scientific Culture “ACCUSTICA”. It is part of an ambitious strategy in terms of science with and for society, promoting exchanges between the world of research and citizens, participating in the progress and strengthening of society. The project aims to cover the entire territory of Champagne in order to develop relations between science and society with a diversified public, as wide as possible. It is consistent with the second wave of “Science With and For Society” labeling for which the University is applying. It therefore integrates three of the four axes of the labeling requested: • Axis 1: promotion of research and its challenges to all audiences and in particular in rural areas and/or priority neighborhoods of the city, • Axis 2: Training in mediation, communication or scientific approach, • Axis 3: Promoting news and scientific expertise in the media. The project brings together six projects eligible by the ANR ( ExoAGEing , HANUMAN, MACRONEU1, MIXSPINDIFF and UrbaTime for URCA and BIOMOD for INRAE) within a common framework of communication, mediation and scientific promotion actions implemented during the 36 months of the project. • The actions proposed within the framework of axis 1 aim to spread science at the heart of society, to exchange and debate with citizens and to create regular meetings between researchers and high school students. We will rely on existing flagship actions such as Classes en Fac, the Cordées de la Réussite or the Fête de la Science. • Training in mediation, communication or scientific approach carried out in axis 2 will be piloted, directed and supervised by ACCUSTICA staff, capitalizing on the experience acquired over 15 years in the field of scientific culture. Active approaches, thus mixing theoretical contributions, role-playing, small group work, games, visits to places of mediation, meetings and exchanges with scientists and the target audience will be favoured. • The writing of popular articles, meetings, exchanges and conferences with the general public will make it possible to promote the results of research from the ExoAGEing , HANUMAN, MACRONEU1, MIXSPINDIFF, UrbaTime and BIOMOD projects .

Pulmonary Arterial Hypertension (PAH) is a rare, incurable and deadly disease of the pulmonary vessel. It is defined by an elevation of pulmonary arterial pressure, due to progressive and obstructive remodeling of small pulmonary arteries, leading to right heart failure. Existing treatments target vasoconstriction, are not curative and it remains an unmet need for anti-remodeling strategy. The only outcome is lung transplantation, with a survival of 50% at 5 years. A new player related to respiratory diseases, the pulmonary microbiota, is not yet taken into account in PAH. Asthma, COPD, idopathic fibrosis, cystic fibrosis are related to a pulmonary pathobiome with a decrease in diversity promoting progression of the disease, acute exacerbations and mortality, thus opening the way to new therapeutic avenues. LUMI aims to explore the pulmonary microbiota as a new actor directly impacting vascular remodeling and the progression of PAH, via its metabolites. The specific objectives are: a/ to determine the physiological impact of the microbiota on the architecture of the developing pulmonary vascular tree, b/ to translationally characterize the pulmonary microbiota in experimental and human PAH and c/ to evaluate the physiopathological and therapeutic consequences of this microbiota and its metabolites on vascular remodeling leading to PAH in a pre-clinical model. One of the challenges will be to demonstrate the link between pulmonary bacterial species, their metabolites and pulmonary vascular remodeling. The other challenge is how to ensure the translation of the initial observations on the pulmonary microbiome composition in PAH patients to pre-clinical models of PAH. Thus LUMI has emerged as a multidisciplinary consortium that brings together 3 complementary expert partners P1 (INSERM UMR_S 999, Paris Sud University/Paris Saclay University), P2 (MICALIS-INRA), and P3 (INSERM UMR_S 1078, UBO), respectively in the fields of Biology/Medicine (Pathophysiology of PAH and Therapeutic Innovation), Functional Metagenomics (METAFUN), and Lung Ecosystem (16S Metagenetics / Metatranscriptomics and MUCOBIOME Bioinformatics pipeline). LUMI has designed a research strategy focused directly on these metabolites, through both a targeted and comprehensive approach, to address these challenges with the unique opportunity of access to explanted lung tissue from PAH patients in relation to the National Reference Center hosted by P1. We believe that whatever the mechanisms leading to altered composition of the pulmonary microbiota – disruption of pulmonary homeostasis, bacterial translocation from intestine along the gut-lung axis, or migration of oropharyngeal bacteria – changes in the structure and diversity of the pulmonary microbiota, its composition and function may have direct effects on pulmonary vascular remodeling leading to PAH, through microbial metabolites produced in the pulmonary microenvironment. Our preliminary results indicate the role of certain targeted metabolites as negative or positive modulators of pulmonary vascular cell proliferation. The expected results of LUMI are: a) to contribute to new knowledge on the role of the microbiota in respiratory diseases, b) to open up and feed a new field of knowledge on pulmonary vascular development, vascular remodeling and pathophysology of PAH c) to lead to a breakthrough in our vision of the pathophysiology and management of PAH patients. LUMI will provide a first knowledge on the pathobiome diversity and the pulmonary microbiota signature of PAH, as a basis for identifying new biotherapeutic approaches, as well as PAH biomarkers based on identified circulating metabolites. The final products that could emerge from LUMI for further development could be based on bacteria or their metabolites. As new therapeutic agents, they could be used in add-on therapy to existing treatments, to restore lung bacterial homeostasis and reverse lung vascular remodeling.