[Extract from the AEF dispatch of January 5, 2022] As part of its drive to promote “science with and for society”, on March 18, 2024 the ANR launched a new call specifically aimed at research projects it had already funded in 2021. The aim is for these winning projects to propose and implement “scientific mediation, communication or promotion actions” on their issues and results, aimed at a non-specialist audience. Submission of proposals to this call, entitled SAPS-CSTI-Générique21, is open until April 25, 2024. This call “aims to implement scientific communication, mediation and promotion actions around the issues, methods and results of research projects supported by the ANR as part of the 2021 generic project calls, under the JCJC (young researchers) and PRC (collaborative research projects) funding schemes”, states the call text. “All forms of scientific mediation, communication and promotion can be envisaged”, emphasizes the ANR. However, “they must be of a structuring nature at local, regional or national level, by jointly mobilizing the project coordinators [...] within the establishments, but also the scientific culture structures [...], and in particular those referenced by the Ocim (Office de coopération et d'information muséales)”. The aim is to create or reinforce a real synergy between scientists and professionals in the fields of scientific communication, mediation and promotion, “backed up by a steering mechanism to ensure the coherence and visibility of the actions carried out”, explains the ANR.

The rapid emergence of numerous SARS-CoV-2 variants poses a global threat to human health and undermines the goal of achieving herd immunity through vaccination. The overarching aim of VERSATILE is to understand the interplay between cell entry routes and host antiviral responses. This will be addressed under the kaleidoscope of the emerging SARS-CoV-2 variants. Our central hypothesis is that SARS-CoV-2 variants can use distinct entry routes to infect cells that differentially impact host antiviral responses. To test our working hypothesis, we will examine infectious entry of SARS-CoV-2 variants by complementary approaches including flow cytometry, qRT-PCR, advanced live imaging, and other high-end fluorescence-based methods. The function of the receptors and entry cofactors of SARS-CoV-2 variants will be analyzed by introducing mutations that impaired their specific functions and cellular location. Additionally, through a mutagenesis strategy in the viral envelope protein spike, VERSATILE will also have a predictive dimension on the pathogenic potential of future variants. In a final approach, our results will be used to guide the identification and characterization of new small molecule inhibitors specifically targeting each entry route used by SARS-CoV-2 variants. To mimic the anatomical site of viral transmission, where innate immune responses are triggered, we will perform our investigation in 3D polarized primary nasal and lung in vitro cell models. The study of the host defense responses will be focused on the plasmacytoid dendritic cells (pDCs) since they were identified as the predominant producers of antiviral cytokines, i.e., type-I and -III interferon, against SARS-CoV-2. VERSATILE will hence pave the way, not only for answering fundamental questions in the virology, cell biology, and immunology of SARS-CoV-2, but also for developing new antiviral strategies against circulating and future coronaviruses.

The aim of the FRiPPon project is to explore an emerging class of fungal peptides, called dikaritins, and to understand their role as chemical effectors in fungi interacting with plants. Fungi produce a wide range of secondary metabolites (SMs) acting as chemical effectors to colonize their ecological niche. In particular, phytopathogenic and endophytic species produce SMs to manipulate the physiology of their host or its microbiote. The recently discovered dikaritins are considered as the main class of ribosomally synthesized and post-translationally modified peptides (RiPPs) in Ascomycetes. The first identified dikaritins attracted attention because they are phytotoxins (Ustiloxins, Phomopsins) or effectors manipulating plant immunity (Victorin). Based on the specific features of the biosynthesis of the five dikaritins identified so far i.e. the need for a precursor protein named KEP (Kexin-Processed Protein) and at least one DUF3328 (Domain of unknown function 3328) enzyme for cyclisation, genome mining studies revealed hundreds of dikaritin biosynthetic gene clusters (BGCs) in fungi, in plant pathogenic species but also in beneficial endophytes. In addition, preliminary transcriptomic analyses indicate that some of the dikaritin BGCs are activated in the presence of the host plants which suggests that they play a specific role in these biotic interactions. The specific objectives of the FRiPPon project are: (i) To discover new bioactive dikaritins from fungi interacting with plants, (ii) to explore their chemical diversity, (iii) to characterize their bioactivities in plants and microorganisms, and (iv) to evaluate their potential in agronomic applications. To reach these objectives, the program will focus on a set of four fungal species with well-characterized interactions with plants and high-quality genomic and transcriptomic data: Botrytis cinerea, a polyphagous necrotrophic plant pathogen, Colletotrichum higginsianum, a plant pathogen with contrasting biotrophic and necrotrophic stages on Arabidopsis thaliana, C. tofieldiae, a beneficial root endophyte of A. thaliana and Leptosphaeria maculans a plant pathogen that shows biotrophic, endophytic and necrotrophic stages of infection on rapeseed. Importantly, the project also includes three Penicillium strains that are beneficial for plant growth and show strong agronomic interest for the industrial partner (CMI Roullier). The main challenge of the project is to isolate dikaritins that are weakly (or not) produced in the absence of the plant. To overcome this technical bottleneck, we will carefully identify the BGCs of interest and express them in a heterologous host i.e. yeast. Then, state-of-the-art techniques will be used to extract and purify the dikaritins and to determine their chemical structures. We anticipate obtaining at least five new bioactive dikaritins that will be further tested on plants and microorganisms. In parallel, fungal genetics studies will be conducted to evaluate the role of these chemical effectors in plant-fungal interactions. FRiPPon is a PRCE that draws together two academic institutes, the BIOGER institute (INRAE) and the MNHN, with expertise in fungal-plant interactions and chemical ecology, respectively, and the CMI – Roullier company that develops natural products for the agronomic industry. On an academic level, this interdisciplinary project is expected to help to decipher how fungi manipulate plant hosts or antagonize competitors in their ecological niche, and to reveal new dikaritin chemical structures. Finally, the exploration of this untapped source of fungal SMs will pave the way for the development of sustainable and natural solutions for use in agronomy.

Structural variation is a major driver of genetic diversity and an important substrate for species adaptation and selection. Understanding the relationships between structural variants and functional innovations thus represents a major issue to be addressed. In allopolyploid species, which are common in angiosperms and particularly widespread in crops, exchanges between homeologous chromosomes (i.e. between constituent subgenomes), called HEs for homoeologous exchanges, represent a major source of structural variants. However, we still know little about the genome-wide distribution and resulting functional diversity generated by these variants even though they may have played a prominant role in the evolutionary success of allopolyploidy in plants. In the EDIn project, we will develop an integrated set of analyses to advance knowledge on the causes and consequences of HEs, from the mechanisms responsible for their formation to their effects on gene and genome expression, on chromatin dynamics and plant phenotypic variation in oilseed rape, Brassica napus. Based on highly original plant material specifically designed to promote HE, combined with state-of-the-art multi-omics approaches, our project will address fundamental questions in the context of the allotetraploidy of the B. napus crop genome. EDIn is composed of three main workpackages. WP1 aims to profile the products of inter-homoeologue recombination at very high resolution and build a predictive model of their occurrence, which would be useful in breeding for managing introgressions in crop x wild relative hybrids. WP2 aims to evaluate the global consequences of HEs on gene expression at genome-scale but also at population level. In particular, it will make it possible to characterise the impact of HE on gene regulation networks, which would represent the first in-depth analysis for an allopolyploid crop. WP3 aims to establish the causality of specific HEs by developing an original genetic association study, and to characterize their impact on the reorganisation of the genomic and epigenomic landscapes. In a highly original manner, WP3 will study the changes in the epigenome and the reorganisation of chromatin that introgression of alien chromatin originating from a HE can cause. Our results should therefore prove fruitful in developing useful knowledge and operational strategies for the improvement and diversification of allopolyploid crops, in particular for the management of their genetic diversity or associated genetic resources. This research will be conducted by a consortium of renowned scientists who bring highly complementary expertise, know-how and/or facilities, allowing a more complete understanding of the impact of HEs on the functioning of the allopolyploid genome. One original aspects of this consortium is its direct link to higher education, which represents an excellent opportunity to teach students about the socio-economic impact of public research and train future researchers in the field of recombination, genomics, epigenetics, chromatin organisation and dynamics, for plant breeding.

The CHLOR2NOU project aims to develop new monitoring tools for CLD and its TPs, to provide new knowledge on the fate and risk of CLD TPs, and to explore realistic alternative approaches for pollution remediation. The postulate of the non-degradability of CLDs commonly admitted for several decades has had a strong negative impact on pollution management by ruling out the possibility of CLD degradation. The representation of CLD in the FWI society and in the scientific community is therefore of paramount importance. The CHLOR2NOU project is divided into 7 Work Packages that bring together scientists from various background: the WP1 with the synthesis of CLD TPs, CLD baits and fluorescent macromolecular cages; the WP2 that deals with innovative analytical methods: (i) routine laboratory method for the detection of CLD TPs in environmental and food matrices, (ii) immunoassay using a CLD-selective antibody, (iii) a semi-high-throughput detection protocol based on the recognition of CLD by a fluorescent macromolecular cage; the WP3 dedicated to toxicological and ecotoxicological studies in order to define the toxicity profile of CLD TPs; the WP4 with several analytical campaigns to obtain a first estimate of the possible exposure to CLD TPs; the WP5 that aims at studying the fate of CLD TPs, in particular in FWI soils, while defining degradation indicators; the WP6 that is focused on the study of realistic agronomic and environmental conditions capable to favor CLD degradation; the last WP centered on the representation of CLD in the FWI society at large. A co-construction method will be used to help the population and stakeholders to better assimilate the scientific results.