Some of the strongest interactions between ecological and climatic processes concern phytoplankton. While the importance of phytoplankton ecology for the global carbon cycle is well established, the role of their evolution is much less so. Adaptation is of particular importance in predicting the system's response to climate change, since it will modulate the ecological response to environmental change. Recent global ocean circulation models account for phytoplankton ecology. Here we propose to refine the definition of ecological processes and to allow for adaptation of phytoplankton cell size and shape in such models, as well as in more strategic models for freshwater systems. Phytoplankton communities are size-structured, and ecological functioning depends strongly on cell size and shape. Furthermore, phytoplankton size will influence the effectiveness of the biological carbon pump, through which carbon is sequestered from the atmosphere into the ocean interior by cell sinking. In addition, phytoplankton dynamics and evolution depend on interactions with higher trophic levels in the pelagic food web and these ecological interactions are generally also size structured. All these properties are shared between marine and freshwater systems. Phytoplankton ecology will be modelled by accounting for physiological structure (cell size, shape, nutrient quota) of phytoplankton communities and the size structure of the entire food web. We will study a range of models covering spatial scales from the global ocean to lakes. Different theoretical issues will be tackled using models at different spatial and temporal scales. The models will be used to formulate quantitative, testable predictions, that will be put to the test in experimental setups (outdoor freshwater mesocosms) and by using ecological and genomic data from the Tara Oceans expedition. The overall theoretical issue to be addressed is: does adaptation accelerate or mitigate the impact of climate change on the global carbon cycle?

Cervical cancer is the third most prevalent gynaecological cancer, after uterine body and ovarian cancers. Occurring in young women, with a peak of incidence around age 40 and death at 55 years, this cancer is one of the most marked by social inequalities. The women of the most disadvantaged social categories are those who combine both the most risk factors and poorer adherence to preventive measures that rely on vaccination against human papilloma viruses (HPV) and screening for early stage cervical lesions, starting at the age of 25 years. As almost every case of cervical cancer could be prevented by cervical screening and HPV vaccination. The different European countries have implemented cervical cancer screening practices, more or less systematic, and more or less effective, with rates of regular screening widely varying. Even in countries where this rate is high, such as Finland or Sweden, some women who are truly refractory to screening. This is a major health issue because these women are often at high-risk with a 5-year survival closely correlated with the stage of disease when discovered. The costs also increase exponentially depending on the cancer stage. Numerous randomized trials conducted around the world have attempted to improve the response rate in underscreened women. But unfortunately the response rate barely reaches 20% of these women. Many factors can explain the difficulties in obtaining a satisfactory screening rate, whether geographic distance, economic constraints, disengagement of general practitioners, education level or socioeconomic status. It is therefore a European public health problem for which we assembled a network of experts from 10 European countries (Belgium, Bulgaria, France, Germany, Ireland, Italy, Portugal, Romania, Spain, and Sweden), three research groups, the International Agency for Research on Cancer (IARC), the European Cervical Cancer Association (ECCA) and the Poverty Action Laboratory (J-PAL), and a representative association of patients, The European Institute of Women's Health (EIWH). These experts, clinicians and researchers, have expertise in screening for cancer, especially cervical cancers, in conducting large randomized clinical trials, in qualitative and quantitative analysis of social and cultural determinants, in analysis of social disparities and discrimination for access to care, or in modelling health policies. If all group members do not all have worked together in the past, numerous collaborations already took place within the group. The goal of our network is to file a research project for the H2020 SC1-PM-10-2017 call for proposal entitled “Comparing the effectiveness of existing healthcare interventions in the adult population.” This project aims to test, in partner countries, interventions to increase adherence to screening in underscreened women, with special attention, but not exclusively, to women of low socio-economic status; to evaluate the quality, and assess its drivers, of downstream management of abnormal screening findings; model interventions in different countries; to analyse the cost-effectiveness of the intervention; and finally to develop an implementation research to define the best strategy through European countries of different socioeconomic structures and disease prevalence levels. The project will be managed by a French coordinator and a steering committee of clinical researchers, and will be promoted and coordinated by the INSERM. The MRSEI funding will be used to strengthen interactions within the group, validate pillars of the program (work packages) and within these pillars refine more specifically questions deserving to be assessed.

The propagation of respiratory diseases involves the expectoration of small droplets, in various manners such as speach, sneeze or cough. A single sneeeze may send droplets up to six meters. Droplets as small as 100nm may contain the SARS Cov 2 virus which has a diameter of approximately 60-140 nm. The natural history and quantitative analysis of these tiny droplets is very poorly known. While droplets of sizes larger than a few microns can in principle be observed experimentally by optical methods, the observation is not easy and the number and physical fate of droplets of small sizes is thus unknown. This motivates the study which is organized on three axes - how many droplets of each size are created in a cough or sneeze in connection with an extensive experience and an intense ongoing effort on the topic of droplet size distribution; - how do small particles diffuse/disperse in the environment (This may seem a well studied topic, but the interaction with turbulence, rheology, multicompositional systems and evaporation dynamics make it much more complex); - how do small particles of mucus liquid dry in the environment both when suspended in air and when deposited on a surface (This topic is related to that of heat and mass transfer from droplets) . The local environment of a micron size droplet in even very moderately turbulent air may be fluctuating so the rate of drying may be a characteristic of air turbulence (just as a hot wire signal) or of local fluctuations in the humidity and temperature. Starting on this basis, the project will be performed in collaboration between the Paris-SU group specialising on theoretical and numerical aspects of atomization and the Cambridge-MIT group. The groups are already involved in collaborative work on the physics of drops, and the MIT group on mathematical-statistical studies of covid transmission. The most typical mechanisms for the production of the droplet size distribution are the hole formation and the ligament breakup mechanism. Both will be reviewed together with an analysis of the ligament size distribution and a re-analysis of the experiments. For a given expectorated mass, the likely ranges of minimum and maximum droplet sizes and the corresponding numbers will be predicted from the literature and previous studies. We stress that the objective of the project is not to perform new experiments or computer simulations of the processes, but organize what is already known in a manner that allows useful quantitative predictions for epidemiologists. In particular, attention will be focused on the aerosol (diameter less than 100 microns) droplet formation mechanisms. These are - the satellite droplet mechanism which leads to the formation of approximately ten times smaller droplets than the main droplets in an atomization process. - the thin sheet/hole perforation mechanism for saliva or mucus, currently unexplored. The diffusion and dispersion of droplets in the environment is a critical process. Micron-size droplets settle to the floor in thirty minutes to eight hours in a perfectly quiet atmosphere, but the situation is much more complex whenever air turbulence, always present to some degree, is taken into account. Turbulent dispersion will considerably increase the range of droplet sizes that remain suspended in air for a long time. The humidity of the air influences the survival of the virus, by affecting its bilipidic layer envelope, thus the dynamics of vapor exchange on small droplets have relevance. As the research will considerably improve our knowledge of the aerosol and large droplet properties, it will have enormous impact on recommendations for transmission reduction. In particular, it is extremely important to exclude or confirm the existence of long distance disease transmission by areosol particles.

Global change linked to temperature increase and ocean acidification but also more direct anthropogenic influences, such as aquaculture, have caused a worldwide increase in the reports of Vibrio-associated illness, affecting humans but also animals such as corals and mollusks. In particular, over the last 4 years, Vibrio splendidus and V. aestuarianus have been associated with recurrent mortality outbreaks of oyster beds (Crassostrea gigas) in France. Investigating the “emergence of Vibrio pathogenesis events” requires the analysis of microbial evolution at the gene, genome and population level, in order to identify genomic modifications linked to increased virulence, resistance and/or prevalence, or to recent host shift. The study of Vibrio distribution on fine phylogenetic and spatial scales has demonstrated that vibrios coexisting in the water column can be divided into closely related populations, which pursue different lifestyles (free living, particle and animal-associated), defined as ecological population. Thus it is possible to analyze animal-associated vibrios in the context of a metapopulation framework, i.e. considering potential overlap or differences of populations collected from spatially and temporally distinct habitats which are connected by dispersal (here oyster and water column). In contrast to species that are pathogenic to humans, little data are available regarding oyster pathogens. Recent advances in genomics along with the availability of specific pathogen free (SPF) oysters will be helpful to resolve our lack of knowledge concerning the emergence of opportunistic oyster pathogens in natural Vibrio populations. The overall aim of this project is to investigate the partitioning of vibrios into ecologically distinct populations at fine environmental and genotypic scales of resolution. This will allow to determine (i) from what types of microhabitats oyster pathogens emerge and, consequently, what types of populations serve as reservoirs of pathogens, (ii) how populations shift during disease events, and (iii) what genomic features correlate to differential microhabitat association (including pathogenesis). To this end, we will use a combination of population modeling, comparative and functional genomic analysis in addition to experimental pathology. In task 1, we will compare the population structure of vibrios in oysters and surrounding water. We will determine to what extent Vibrio populations are assembled neutrally in oysters or whether specific colonization processes occur and result in association with specific populations. Further, we will determine how Vibrio population structure changes during pathogenicity events. Even if population assembly is overall neutral, one can expect that during pathogenicity events specific genotypes or groups of genotypes outgrow others, resulting in a characteristic shift in population structure. In task 2, we will determine the pathogenicity potential among large numbers of Vibrio strains representative of ecological population. Using SPF oysters, we will test how strains and genotypes affect host survival. These data will be correlated with genome analyses of 100s of strains used in these experimental infections to build hypotheses of gene function in the context of oyster pathogenesis. These hypotheses will be tested by molecular genetics approaches. In task 3, we will investigate the function of observed V. splendidus diversity in diseased oysters. Oysters will be challenged by pools of strains, individually assayed for pathogenesis in task 2, and both colonization and virulence will be assessed. These analyses will enable to determine whether or not colonization efficiency is linked to virulence. If we detect pools showing a higher virulence than that of their individual constituents, comparative genomic analyses will be performed to enable prediction of sets of genes that promote virulence in combination but not singly.