ERC FUNDED PROJECTS

The enormous versatility of bacteria enables the formation of multi-species communities that colonize nearly every niche on earth, making them the dominant life form and a major component of the biomass. Exchange of molecular information among neighboring bacteria in such communities, as well as between bacteria and proximal eukaryotic cells, is key for bacterial success. Yet, the principles controlling these multicellular interactions are poorly defined. Here we describe the identification of a bacterial protein complex, herein termed CORE, whose function is to traffic cytoplasmic molecules among different bacterial species, and between pathogenic bacteria and their human host cells. The CORE is composed of five membrane proteins, highly conserved across the entire bacterial kingdom, providing a ubiquitous platform that facilitates both intra- and inter-kingdom crosstalk. Our preliminary data support the idea that the CORE acts as a shared module for the assembly of larger apparatuses, executing this universal molecular flow among organisms. We propose to elucidate components, structure and biogenesis of the CORE machinery, operating during bacteria-bacteria and pathogen-host interactions. We further aim to provide an unbiased-global view of the extent and identity of cytoplasmic molecules traded via CORE including metabolites, proteins and RNA, and to reveal the criteria determining the specificity of the transported cargo. Furthermore, we intend to decipher the impact of CORE-mediated molecular exchange on bacterial physiology and virulence, and devise anti-CORE compounds to combat pathogenic bacteria. This study is expected to transform the way we currently view bacterial communities and host-pathogen interactions. We anticipate these findings to lead to the development of creative strategies to modulate, predict and even design bacterial communities, and lay the foundation for new and innovative approaches to fight bacterial diseases.

6 930 796 €

Start date: 2019-04-01, End date: 2025-03-31

Clouds play a lead climatic role, controlling energy fluxes and regulating fresh water distribution. There is an acute need for cloud-resolving and global-climate models that accurately describe and parametrize the physics of warm convective and stratiform clouds, and the clouds’ sensitivity to environmental changes. Currently this requirement is not being met due to a gap in observational capabilities. Namely, there is a lack of sufficient sensing tailored to capture the 3D macro and microphysical properties of warm clouds, which are often spatially unresolved. Moreover, current retrievals use a plane-parallel radiative model, which is incompatible with the 3D heterogeneous nature of clouds. These gaps lead to uncertainties in climate models and prediction. We propose an innovative sensing approach: cloud scattering-tomography, relying on an unprecedented large formation of ten cooperating, high performance pico-satellites. They will simultaneously image cloud fields from multiple directions, at 50m resolution. Based on this data, the novel tomography approach will seek the 3D volumetric structure of cloud fields, base-to-top profiles of droplets' size and their variance, volumetric distribution of optical extinction and rain indicators. The required pointing accuracy, data size and coordinated control of a complex 10 pico-satellite formation demands advanced space engineering, beyond existing technologies of traditional single satellites and constellations of satellites. Realizing a large formation requires innovative, distributed, networked, cooperative control, including advanced sensors and actuators for pico-satellites, as well as in-orbit autonomy. On-board hardware and flexible software will be adapted to meet computational needs within the physical limitations of pico-satellites (energy, mass, volume). Using the acquired spaceborne images for tomography-based 3D atmospheric retrievals requires advancements in computer vision and efficient analysis based on three-dimensional radiative transfer. New information gained will improve and validate our cloud resolving models, leading to more realistic simulations of cloud fields. This will enable better understanding of how environmental changes affect warm clouds and help improve their representation in climate models. This multidisciplinary, synergic approach will establish and test critical and currently unconventional aspects of remote sensing and mathematical retrieval based on a pico-satellite formation. It will yield a database of 3D macro and micro structure of warm cloud fields, while setting the stage for next-generation distributed spaceborne global observations.

13 878 593 €

Start date: 2019-08-01, End date: 2025-07-31

During craniofacial development, Cranial Neural Crest Cells (CNCCs) maintain broad plasticity and patterning competence until they make appropriate cartilage and bone structures in response to local cues. We found that CNCC embryonic plasticity involves a specific epigenetic chromatin signature that maintains genes, including Hox genes, in a transcriptionally silent but poised state, so that they can be readily switched to an active state in response to position-specific environmental signals. Are there CNCC-derived subpopulations in the adult face cartilage with similar broad plasticity properties that could be used as progenitor source in regenerative medicine? We have shown that Hox-negative adult human CNCC-derived Nasal Chondrocytes (NCs) have cartilage regenerative capacity and plasticity to adapt to heterotopic sites larger than other cell sources, and demonstrated their potential clinical use for articular cartilage repair. However, lack of understanding of the involved molecular mechanisms limits the broader utilization of adult NCs for the regeneration of other cartilage types, e.g. the intervertebral disc (IVD). This proposal will establish fundamental understanding of the biological processes responsible for the plasticity of adult human NCs and offer a paradigm example of scientific and clinical synergies bridging developmental (epi)genetics and regenerative medicine. We will: • Establish whether Hox-negative adult NCs and embryonic CNCCs share similar transcriptomes, epigenomes and 3D chromatin architectures using single cell RNA-seq, ChIP-seq and capture HiC-seq assays. • Assess whether NCs can epigenetically and transcriptionally adapt to the Hox-positive IVD environment, using co-culture and bioreactor-based organ culture models, and investigate the underlying molecular mechanisms. • Verify the capacity of adult NCs to repair degenerated IVD cartilage. • Use human autologous NCs for repair of IVD degeneration in a phase I clinical trial.

5 330 000 €

Start date: 2019-03-01, End date: 2025-02-28

European societies today face unprecedented environmental change. Understanding how human societies responded to past challenges of environmental change relates to the interface between culture and environment. The EXPLO project proposes a novel interdisciplinary approach to investigate key questions regarding the interaction between past human ways of life, land use and the wider environment through a unique combination of archaeological, biological and dynamic mathematical modelling approaches. Archaeological prehistoric sites in lakes of northern Greece and the southern Balkans provide an excellent opportunity to investigate rich archives of societal and environmental change in the cradle of European farming. Natural lake sediments and submerged prehistoric settlements offer exceptional preservation conditions and uniquely holistic insights into past anthroposphere, biosphere and geosphere dynamics. More than 8,000 years ago, technological and social breakthroughs allowed the introduction of farming from western Asia to Greece and thus for the first time to Europe; however, so far there is no high-resolution picture of how this revolutionary innovation interacted with the environment, including its long-term consequences. New underwater archaeological research will allow the construction of highly precise settlement chronologies on the basis of dendrochronology, radiocarbon dating and Bayesian modelling. On-site information from excavations will be combined with off-site palaeoenvironmental data from the same lakes to investigate past adaptation strategies to the environment as well as the effects of past societies on their environments. Dynamic models integrating archaeological contexts and palaeoenvironmental data will open up the opportunity to investigate vulnerability, resilience, tipping points and thresholds of ancient agrarian economies, with implications for future food systems under a rapidly changing climate.

6 403 199 €

Start date: 2019-03-01, End date: 2024-02-29