Background: In 2017, World Health Organization reinstated snakebite envenoming to its priority list of neglected tropical diseases. In France, concern is related to the fashion of maintaining exotic snakes as pets, whereas Bothrops sp. are responsible for life-threatening envenomations in French guyanan and Martinique. Local signs include pain, edema, and soft tissue necrosis, whereas systemic effects are incoagulable blood, spontaneous bleeding, and major endothelial dysfunction. Bothrops antivenoms are the only specific treatment to counteract envenoming, whereas their clinical efficacy has been rchallenged. Specific rationale of the research program: In most cases, chosen antivenom starts hours after the snake accident; thus, tissue inflammatory process is well advanced at the time of immunotherapy. Despite potent inhibition of circulating toxins by antivenoms, Bothrops snakebite can trigger overwhelming systemic inflammatory host response (SIRS), leading to multiple organ system failure and death. Central to sterile SIRS are recognition of “sensing danger” motifs such tissue damage-associated molecular pattern molecules (DAMPs). DAMPs induce inflammation through recognition by Toll like receptors (TLRs) and NOD-like receptors (NLRs), activating transcription factors and inflammation. Hypothesis of the research program: We state that Bothrops snakebites can induce overwhelming SIRS triggered by venom-associated molecular patterns (VAMPs) and DAMPs signaling. Regarding “danger motifs”, DAMPs release from mitochondria (mtDAMPs) is of critical importance due to their ancestral microbial origin. We state that mtDAMPs may be released from either injured bitten tissues or secondary to increased cell membrane permeability of target organs in response to exposure to Bothrops venom toxins. In addition, mitochondrial dysfunction elicited by severe envenomations will disrupt fine tune regulation of innate immune response through mechanisms involving oxidative stress, cardiolipin externalization, and impaired mitophagy. Preventing mitochondrial dysfunction by mitochondria-targeted antioxidants would thus able to improve severe Bothrops envenomation. Results and discussion: Our results will depict venom components and immunorecognition neutralization by antivenoms of Bothrops sp. endemic in French oversea areas. Second, preclinical studies in Bothrops venom–treated mice will reproduce features of pathophysiological profile observed in human, such as local edema/necrosis and systemic hemorrhage. Our study will also demonstrate for the first time that Bothrops envenoming induce inflammation through signaling pathways including TLRs and NLRP3 inflammasome activation. Third, our results will demonstrate that intravenous Bothrops venom induces mtDAMPs release, thus indicating that VAMPs may directly induce DAMPs release independently of venom-induced local injuries. Translational studies in human will show that Bothrops snake venom mixtures impair mitochondrial function and induce mtDAMPs release in ex vivo human preparations of cardiac cells and artery vessel rings. Our results will show that Bothrops toxins induce mtDNA release, mitochondrial dysfunction, abnormal vasorelaxation and endothelial cell dysfunction, which are all prevented by mitochondria-targeted antioxidants. Importantly, these results will be translated into new medical practice. Pilot clinical trials in Martinique and French Guyana will be promoted to demonstrate that elamipretide, an effective mitochondria-targeted antioxidant previously approved for clinical use, improve mitochondrial dysfunction, blunt inflammation and prevent multiple organ failure in severe Bothrops envenomation. Conclusion: Overall, our efforts will identify new pharmacological mitochondrial targets that control the inflammation process in its early stage and provide new complementary treatments to traditional antivenom immunotherapy for Bothrops envenomation.

Science has undergone, since the end of the XX century, a biotechnological development hardly imagined some years ago. Genetics, medicine and new technologies have transformed human reality as we knew it up to now, raising serious ethical doubts. Is everything technically possible also acceptable in ethical terms? And if so, where are the legal limits? In Biolaw it converge science to reach an advanced knowledge, ethics to question the limits and the complexity of realities and law to offer a fair response. However, the professional world and the academia lack the skills, the training opportunities and the necessary resources to cope with these problems. With this project, we hope to create a mass of well trained lecturers and professionals in the field of Biolaw at each partner institution in Costa Rica and Mexico. On the basis of the existing offer and demand, we will develop 4 capacity and 2 doctoral courses online, focused on research skills and on Bio-law specific topics. We will support the launch of a new joint doctoral programme in Mexico and will support its expansion with 1 more university in Mexico and 2 new in Costa Rica. The courses will be developed and taught online and in 3 different languages (English, French and Spanish). The new academic offer, together with a set of training and dissemination activities –international seminars, conferences and stays abroad- and the help of new elearning and bibliographical equipment, will come to integrate the partner’s doctoral and lifelong learning offer, contributing this way to the emergence of a critical mass of well trained lecturers and professionals and to its further development, also at international level.The project will surely impact not only in partner institutions, improving their accessibility, visibility and their capacity of attraction and influence, but also in the public and private sectors of Health, Environment a Law in the partner regions and countries.

Our proposal to the ANR MRSEI call concerns the improvement of the structuration and coordination of the international network (consortium) to develop a European project called “Social appropriation of knowledge, science and technology in sustainability projects “ (ASEPPS). The ASEPPS project will be presented in the Horizon Europe call, MSCA RISE 2021. According to the rules of the previous calls, the ASEPPS project is structured around international exchanges between partners from both groups of countries: the European Union’s participants (France, Ireland and Romania) and Latin America’s participants (Colombia, Argentina and Costa Rica), with the objectives of training and mutual transfer of knowledge, know-how and good practices in the field of research and innovation. ASEPPS aims to contribute to the sustainable development of climate-neutral local social practices through the implementation of green or low-carbon technologies. This objective will be achieved through joint actions in training-education, research and development of technology and innovation, carried out in the framework of the reciprocal international mobility of the partners. The main topics addressed will be energy, water and housing. The studies will focus on: - Using renewable energies (solar, biomass, waste) - Improving the local environment/neighbourhood: energy supply, quality of water, housing with local materials,... - Scientific education and multidisciplinary life-long learning education Taking into account local traditions, socio-economic characteristics as well as environmental conditions, the EU project will assess the social appropriation of the solutions (equipment, procedures, etc.) proposed through a collaborative study taking into account their participation in the structuring, sustainability and results of implementation on site. The technological solutions, with low carbon emissions, will be applied on several pilot sites where the partners are already developing research activities. The work of building the future EU projects ASEPPS with a consortium of partners started at the beginning of the year 2020. It accelerated with the creation of the logistics group COLIFRI– IMT Mines Albi. However, as it is a new consortium, the ANR funding can help significantly to mature this research and training network as it requests an important coordination task to make sure the European project proposal is made in good conditions to succeed. The initiator of the project, COLIFRI, is a Franco-Colombian association for research since 2018, supported by the French Embassy in Colombia and Colombia’s government (https://www.colifri.com/fr/qui-sommes-nous/). It brings together nearly 400 researchers and about forty-partner universities. IMT Mines Albi, an historic partner of several Colombian universities and the French Embassy in Colombia, was chosen as coordinator of the future project of ASEPPS, in charge of developing and submitting the European ASEPPS project. IMT Mines Albi is part of Institute Mines-Te´le´com (IMT), a French Higher Education and Research institute, comprised of 8 core-engineering schools, plus 5 affiliates. IMT is France’s largest engineering higher education and research institute. With over 13,000 students, including ~1,500 PhDs, over 1,300 professors/researchers and 500 international partnerships, IMT represents excellence in its endeavour to innovate for impact. IMT has been participating in more than 130 Horizon 2020 projects and plays a major role in Horizon 2020 by acting as National Contact Point (NCP) for the ICT programme as well as for a National Contact Point for Horizon 2020 programmes for SMEs.

Cultural heritage, origin products and biodiversity in rural areas are often underutilized or exploited according to short-term logics. SUS-TER addresses the need of developing specific knowledge, skills and abilities for the elaboration and support of inclusive and sustainable territorial valorization of these local resources. SUS-TER will develop a new interdisciplinary profile of “Territorial Enhancer” capable to activate and facilitate these processes of sustainable valorisation. He/she will be able to design and implement: - local forms of interaction between resources, society and local economy, applying a territorial development paradigm - local systems of governance of biocultural rural territories and associated knowledge and know-how- territorial marketing plans, applying methodologies that allow local enterprises to participate in markets competitively, sustainably and inclusively.This general aim will be pursued by means of the design, elaboration and testing delivering of an innovative course, based on the concepts of modularity, integration of theoretical and practical knowledge, blending of different learning methods, recognition within existing HEI curricula. Territorial laboratories will play a key role in the methodology, allowing for the integration of knowledge and practice by means of a learning space linking teachers, producers, entrepreneurs and public authorities. The course will be delivered at international level and within each university. It will be recognized by the Universities according to their institutional rules, as such or as part of existing curricula. The course and teaching materials will be in Spanish. Preliminarily, a specific training for academic staff will be carried out.SUS-TER will impact students and Universities, but also SMEs, NGOs, collective organizations, international, national and local development agencies, allowing for inclusive and sustainable processes of valorization of rural heritage.

Ecosystem degradation and biodiversity loss may facilitate the emergence of zoonotic diseases. The 4-year ZOE project will analyze the links between landcover and land use changes in tropical biodiversity hot-spots facing loss of primary forest and biodiversity and in temperate regions that have undergone ecosystem degradation and deforestation over historical timescales. In areas experiencing different levels of ecosystem degradation, biodiversity assessments will be based on remote sensing-based GIS analysis of landscape structures, geobotanic plant mapping, and targeted trapping of rodents, ticks, and mosquitoes, as prototypic reservoirs and vectors of zoonotic diseases (macro-organism scale). Host- and soil-associated microbiome and virome high-throughput sequencing will be combined with assessment of human exposure to prototypic zoonotic pathogens, using high-throughput serological analyses (microbiological scale). ZOE will link with local communities and stakeholders to address perceived land use and land cover changes, disease occurrence, coping strategies, and risk behaviour. Results will be synthesized in modelling and risk mapping frameworks linking biodiversity loss and zoonotic disease risks and tested in forecasting scenarios to feed into cost-efficient monitoring schemes and early warning systems. An online knowledge platform will be created to link all relevant stakeholders of the biodiversity-health nexus, including other EU-funded consortia, national and supranational organizations stakeholders, local communities, and the public. A joint stakeholder conference will be organized, and community engagement workshops will specifically co-create and advance knowledge in local communities involved in ZOE. The ZOE project is proposed by an interdisciplinary consortium with expertise in geography, geobotanics, ecology, virology, immunology, epidemiology, sociology, psychology, anthropology and science dissemination from 7 EU and 4 American countries.