In the past decade, nations have reinforced their domestic plans and networks to handle biothreats, as illustrated through the following French and German examples. In recent years, academic labs and the CBRN industry have proposed technological answers for the identification of biological (B) agents in the field or in laboratories. A range of biosensing technologies based on various principles (nucleic acid hybridisation, affinity sensors, enzymatic sensors…) have been developed ranging from proof-of-principle to more or less advanced Technology Readiness Levels. However, in the case of an intentional release of these agents, experts in France and Germany have identified different technical obstacles and major gaps in these detection technologies which prevent a timely and comprehensive analysis and response. Although there are various initiatives at state level there is no European accepted / established commercial technology which aims at reliably detecting a broad range of all different relevant biological agents (bacteria, viruses and toxins). In this context, GEFREASE (GErman FRench Equipment for Analysis and Surveillance of biothreats in the Environment) proposes to answer main issues associated with the detection of potential biological warfare agents. On the basis of previous experience gained by the four project partners, we will develop an integrated diagnostic approach combining on-site detection systems (provisional detection) based on immunoassays and confirmed and precise identification methods based on state-of-the-art mass spectrometry. We will target both toxins (ricin, botulinum toxin serotypes A, B, C, D, E, F, staphylococcal enterotoxin A and B, abrin) and microorganisms (Francisella tularensis, Bacillus anthracis, Yersinia pestis, Vibrio cholerae and pox virus) which all belong to the most powerful agents of biological threats. Our technologies will be able to detect and identify the presence of these potential agents in different environmental media (air, environmental and consumable waters, and drinks such as milk), advancing existing technologies available within the consortium which have been developed for clinical microbiology testing so far. GEFREASE project associates four partners, among them two academic institutions: the CEA (Commissariat à l’Energie Atomique, Atomic Energy Commission, Marcoule), a research body with a technological focus on defence and healthcare technology and the Robert Koch-Institut (RKI, Berlin), the central federal institution responsible for disease control and prevention in Germany which is also as a reference institution for both applied and response-orientated research as well as for the Public Health Sector. Two industrial partners will be associated to the project: Bruker Daltonik (BDAL, Leipzig) which has a long standing experience in development and manufacturing devices and applications for mass spectrometric analysis of biological and chemical substances and Bertin Technologies (Bertin, Montigny-le-Bretonneux) which delivers a complete innovation offer, from technology services to delivery of high-tech-products in life sciences and biotechnology processes. The CEA will be responsible for the project coordination and management. By creating a network of experts from France and Germany working in this field, GEFREASE will help to obtain a sustainability of successful detection technologies, which have been developed so far at national level within both countries and to close gaps in detection technology in order to improve health and security for citizens in both countries. The combination of leading industrial partners and scientific / federal institutions in the area of B-detection will enable marketable solutions for provisional on-site detection and confirmed lab-based identification with the potential to open an European and world-wide market

Biological toxins are a focus of concern by public health and law enforcement on national and international levels due to the increasing threat of their deliberate release in a bioterrorist attack. Among these biological toxins the plant toxins ricin and abrin are of particular interest owing to their worldwide availability, ease of preparation, high morbidity and the lack of medical countermeasures. Over the last decade, they attracted much attention regarding criminal and terrorist misuse, culminating in the last-minute prevention of a bioterrorist attack using ricin in Cologne, DE, in 2018 which was preceded by similar terrorist activities in an earlier stage in France. Those biotoxin incidents challenged both countries: If a bioterrorist attack with ricin had occurred, public health and law enforcement would have been overwhelmed. There are no advanced management plans on how to respond to such a bioterrorist attack with ricin or abrin. On-site detection and laboratory confirmation has to be improved, methods for molecular forensics developed and new therapeutic approaches applied. The present project arises from discussions between first responders, special units and end users from public health and law enforcement in France and Germany (Direction Générale de la Police Nationale/DGPN; Bundeskriminalamt/BKA and Robert Koch-Institut/RKI) with scientific experts (Commissariat à l'énergie atomique et aux énergies alternatives/CEA and RKI) where gaps in preparedness and response to bioterrorism incidents with ricin and abrin were identified. We have built a project which starts from the requirements of first responders from public health and law enforcement being responsible for incident management after a deliberate release of ricin/abrin in a public building. To answer the first responders’ and authorities’ needs, we aim at optimizing our existing detection technologies including enzyme immunoassays, mass spectrometry, molecular biology and -omics technologies with potential for industrial exploitation. The approaches will be designed to be applied in a coherent detection and alert procedure including on-site detection and incident management, comprehensive laboratory confirmation and decontamination. A focus will be laid on molecular forensics which aims at providing yet not available information to identify perpetrators and stop subsequent attacks by precisely linking a biotoxin found at a scene to a source identified at a suspect based on unique, identifiable patterns characteristic for the agent. Targeting the current lack of medical countermeasures, we propose novel pharmacological agents for therapeutic intervention based on combination of antibodies and chemical drugs available and pre-tested in France and Germany. By combining the efforts in FR and DE in a synergistic approach, significant progress towards experimental drugs is expected including a concept for evaluation and provision of countermeasures in a case of a bioterrorist attack with ricin/abrin. A trusted scientific collaboration between the CEA and RKI in the field of CBRN (a former ANR-BMBF program and a current European project) will be the frame of the scientific proposal. By the involvement of first responders and special units from law enforcement and public health DGPN, FR, as well as BKA and RKI, DE, the established technologies and operating procedures will be evaluated in two final exercises highlighting the inter-operability of public health and law enforcement and covering essential steps in responding to a bioterrorism attack using plant toxins: management, detection, forensics and therapeutics.

The advent of high-throughput approaches has revolutionized the way we address biological circuits and their complex interrelation during infectious processes. Deciphering the molecular mechanisms underpinning pathogen-host interaction (PHI) is now dealt with in the context of systems biology, which is critically dependent upon our ability to analyze Omics data (whole genome sequence, whole exome sequencing, RNA-seq, proteomics, etc.) derived from both the pathogen and its host. The Institut Pasteur de Tunis (IPT) has for long been working at the interface of PHI, aimed at better delineating critical aspects governing pathogenicity and disease transmission. Through this twinning project, referred to as PHINDaccess (Pathogen-Host INteraction Data access), IPT intends to empower its capacities to efficiently exploit the extraordinary potential of Omics data generated in the context of PHI studies. PHINDaccess should in fine streamline the discovery of critical regulatory interactions, thus allowing for the rational identification of putative biomarkers, drug targets and/or lead vaccine candidates. PHINDaccess main objectives are threefold: (i) endow IPT researchers with advanced knowledge and skills in Omics science, (ii) provide IPT with an efficient high-performance bioinformatics environment, and (iii) ambition to make IPT a regional flagship for excellence in innovative Omics research with increased networking and openness to the socioeconomic sector. To achieve this goal, IPT will twin with world-renowned European centers, namely the Institut Pasteur, the Max Planck Institute for Molecular Genetics, the Center for Genomic regulation, and the Robert Koch Institute, with whom previously EC-funded collaborations have been successfully achieved.

Biodiversity in Afrotropical forests is declining dramatically due to deforestation and intensified bushmeat trade. At the same time there is an increased frequency of outbreaks of emerging infectious diseases (EID) that have a natural reservoir in wild small mammals. The effect of biodiversity changes on the risk of spillover of these EID to humans is not yet clear. Higher biodiversity may reduce transmission rates in the small mammal community (“dilution effect”) or may facilitate it (“amplification effect”). Biodiversity changes may also be associated with changes in human behaviour that affect contact rates with wildlife. BIODIV-AFREID will explore these relations in different forest sites in DR Congo and Côte d'Ivoire. The consortium consists of European and African partners with strong zoological, ecological, biomedical, virological and anthropological expertise, vast experience in field work in Africa and a history of earlier collaborations. We will investigate a range of viral pathogens but with a focus on two contrasting EID that are of major concern: Monkeypoxvirus (found in a variety of small mammals and with frequent human infections) and Ebola virus (with rare spillover events to humans and the reservoir not yet identified with certainty). In areas where these EID have been reported before, we will select sites with differences in forest degradation and bushmeat hunting and describe the biodiversity of small mammal communities (WP1) and the presence and prevalence of the viruses in these communities (WP2). The work will be based on newly collected material as well as considerable amounts of samples that different partners collected during earlier fieldwork. We will then test hypotheses about dilution and amplification effects (WP3) and about the ecological and anthropological conditions that facilitate spillover to humans (WP4). Two additional WP include activities to ensure stakeholder engagement (WP5) and project coordination (WP6). With BIODIV-AFREID, the relations between biodiversity and emergence of new infectious will be better understood and these insights can form a basis for more targeted conservation and public health strategies.