Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DENZUAC (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499996.0 €

Biocatalysis is a key component of the transition towards a more sustainable and “greener” chemistry. Surprisingly, natural enzymes use only a relatively small section of “reaction space”, that is, only limited number of reaction classes. This in marked contrast to the vast reaction space available to the synthetic chemist. Therefore, it is highly desirable to have enzymes available for the catalysis of these abiological reactions. With the advent of robust expanded genetic code methodologies, it is now feasible to introduce a wide variety of unnatural amino acids into proteins. We envision that the time has come to use this breakthrough technology to create enzymes that contain abiological reactive groups as catalytic residue, for the catalysis of reactions that are not possible using canonical amino acids only. The global aim of this project is the creation and application of designer enzymes with genetically encoded unnatural amino acids as catalytic residue for novel and new-to-nature catalysis. The following research objectives are key to achieving the overall aim: 1. Achieving incorporation of unnatural amino acids containing organocatalytic side chains in proteins. 2. Creation of a library of novel designer enzymes containing unnatural amino acids as catalytic residue. 3. Application of these designer enzymes in catalysis of important reactions that have no equivalent in nature. 4. Directed evolution of designer enzymes featuring unnatural amino acids as catalytic residue. 5. Application of designer enzymes containing UAAs as catalytic residue in biocatalytic cascades. This highly ambitious project combines frontier chemical and biochemical research and will deliver completely new classes of enzymes that can access new and previously unexplored parts of biocatalytic “reaction space”. In this way, this project will contribute to achieving the important societal goal of achieving greener and more sustainable approaches to chemical synthesis.

Mots-clés : biocatalysis,designer enzyme,unnatural amino acid,expanded genetic code,stop codon suppressionenantioselective catalysis,directed evolution
Projet ERC : LIFEPLAN (Horizon 2020, appel 2019, Synergy grants)
Entité participante : California academy of science — Pays : Madagascar — Rôle : PI
Acronyme de l'entité : Madagascar biodiversity center, cas madagscar
Type d'entité : Recherche
Financement ERC de l'entité : 620685.0 €

Biodiversity underlies ecosystem functioning. To achieve the basis for a sustainable management of natural resources under current environmental change, we thus need a unified theory of the forces structuring vast sets of ecosystems and taxonomical groups on Earth. For the first time, such a synthesis is now within reach, based on a recent revolution in sampling methodology, globally relevant ecological data, and advances in statistical methods for linking immense data to community ecological theory. In LIFEPLAN, we bring together the key expertise needed to generate and interpret Big Ecological Data for a global synthesis of biotic patterning across our planet: world leaders in community ecology, methods for automated species recognition, and Bayesian statistics for immense data. Our objectives are to generate a new understanding of biodiversity patterns and dynamics by developing fundamentally new methods for big data statistics. To this end, we will generate fully standardized, global big data on a range of species groups, thus allowing quantification of variation in ecological communities at spatial scales covering six orders of magnitude (from 0.1 km to 10000 km), across tens of thousands of species. The resulting data motivate the development of transformative big data statistics, in particular highly scalable algorithms for spatio-temporal data, as well as methods for automated species identification from DNA, audio and image samples. As a key deliverable, we will develop global joint species distribution models describing the spatio-temporal structure of life on Earth. Working together will allow each of us to tackle what we regard as the ultimate challenges in our own fields, while simultaneously collaborating around solutions changing the face of modern biodiversity science. Now is the time for this project, as the big data and big methods emerging today coincide with a great need for global understanding of biodiversity structure and dynamics.

Mots-clés : global patterning of life,big data science,automated species recognition,high throughput data generation,community ecology,biodiversity science,bayesian statistics,scalable methods,hierarchical patterns and processes,joint species distribution modelling
Projet ERC : BIOFAGE (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1368838.0 €

Biofilms are antibiotic-resistant, sessile bacterial communities that occupy most moist surfaces on Earth and represent a major mode of bacterial life. Another common feature of bacterial life is exposure to viral parasites (termed phages), which are a dominant force in bacterial population control throughout nature. Surprisingly, almost nothing is known about the interactions between biofilm-dwelling bacteria and phages. This proposal is designed to fill this gap using a combination of novel methodology, experimental systems, and mathematical modeling. We have recently developed a new microscopic imaging technique that allows us to image and track all individual cells and their gene expression inside biofilms. First, we will use this technique for tracking the population dynamics of bacteria and phages within biofilms at single cell resolution. By genetically manipulating bacterial hosts and their phages, and by varying environmental conditions, we will investigate the fundamental biological and physical determinants of phage spread within biofilm communities. Second, we will study how biofilms respond to phage attack on both intra-generational and evolutionary time scales, focusing in particular on proximate response mechanisms and the population dynamics of phage-resistant and phage-susceptible cells as a function of biofilm spatial structure. Lastly, we will combine our novel insights to engineer phages that manipulate the composition of biofilm communities, either by subtraction of particular bacterial species or by addition of novel phenotypes to existing biofilm community members. Altogether, the proposed research promises to uncover the major mechanistic and evolutionary elements of biofilm-phage interactions. This combined work will greatly enrich our knowledge of microbial ecology and motivate novel strategies for bacterial biofilm control, an increasingly urgent priority in light of widespread antibiotic resistance.
Projet ERC : RG.BIO (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : National Research Council — Pays : Italie — Rôle : PI
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 2211250.0 €

Biological systems displaying collective behaviour are characterized by strong spatio-temporal correlations, which partly transcend the multiform diversity of their microscopic details, much as it happens in statistical physics systems close to a critical point. Recent experiments show that collective biological systems conform to another hallmark of statistical physics, namely scaling. Scaling laws have been found to be valid both at the static and at the dynamic level, although with critical exponents unlike any known model. Building on the experimental evidence of strong correlations and scaling laws, I will develop a novel renormalization group (RG) approach to strongly correlated biological systems, with the purpose of classifying into new universality classes the collective phenomena of life. The key theoretical idea of the method is to perform an expansion around an equilibrium field theory in which the interaction network between the individuals in the group is fixed, and to assess the stability of the resulting RG fixed points with respect to weak off-equilibrium effects, complementing the RG flow with the standard loop expansion around the upper critical dimension. The renormalization group will allow us to go beyond the hydrodynamic regime of small fluctuations, thus pushing theoretical prediction into the critical region of the parameters, where the correlation length scales with the system's size, a region experiments show to be inhabited by several biological systems. To define the starting field theory in the most economic way I will study the role of effective symmetries in giving rise to weakly conserved quantities and non-dissipative terms, and assess their stability under the RG flow. Finally, my lab will conduct new experimental campaigns on flocks (starlings, swifts), swarms (midges, mosquitoes) and cell colonies, to explore and test the new universality classes identified by the renormalization group approach.

Mots-clés : renormalization group,field theory,collective behaviour
Projet ERC : PyroTRACH (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 100000.0 €

Biomass burning (BB) is a significant contributor to global atmospheric particulate matter, with strong impacts on climate, ecosystems and public health. Yet these impacts are highly uncertain, largely owing to our inability to track BB particulate matter and the evolution of their properties throughout most of its atmospheric lifetime. PyroTRACH will provide the necessary breakthroughs in our understanding of BB particles and their impacts by: i) deriving new markers of biomass burning with an atmospheric lifetime that exceeds the current limitation of about a day, ii) measuring highly uncertain but critically-important climate- and health- relevant properties of aerosols both from wildfire events that occur during summertime and from BB for heating purposes during wintertime in highly populated urban environments, iii) applying this new knowledge to quantify the contribution of biomass burning to aerosol in the Mediterranean region, and quantify its impacts on climate and public health. Novel state-of-the-art instrumentation, portable environmental chambers and well established measurement techniques will be applied in continuous measurements as well as intensive field campaigns to study the properties and evolution of BB particulates as they age in the atmosphere. Discovering new stable chemical markers that allow detection of BBOA many days after emission, while carefully and accurately following the climate and health-related properties of freshly emitted and aged BBOA, allows for an unprecedented understanding of the evolution and impacts of biomass burning aerosol and its impact on the Earth System and public health. Considering the increasing occurrence of wildfires, along with decreased emissions from fossil fuels means that accurately predicting the health and climate effects from biomass burning aerosol is one of the most important aspects of atmospheric aerosol that needs to be studied.

Mots-clés : biomass burning aerosol,reactive oxygen species,atmospheric measurements,modeling
Projet ERC : HawkEye (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2492266.0 €

Birds have been called “une aile guidée par un oeil”, and whilst they possess many senses besides vision, their wings are indeed guided largely by their eyes. Nevertheless, we know surprisingly little of how birds use vision to guide their flight, and almost nothing of the underlying guidance and control laws. This is an extraordinary omission, and unfortunate given the importance that vision is poised to assume in autonomous unmanned aircraft. With good reason, the law still requires a human eye to remain in the loop, but as with the coming revolution in driverless cars, the future of flight lies in autonomy. I see a once-in-a-career opportunity here: we need only imagine a hawk, shooting over the top of a hedgerow then plunging through the undergrowth onto its fleeting prey, to see what engineering could learn. Building upon the success of my ERC Starting Grant on Bird and Insect Flight Dynamics and Control, my proposed Consolidator Grant has two overarching ambitions: 1) to revolutionize our understanding of vision-based guidance and control in birds; and 2) to carry these insights over to application in unmanned autonomous aircraft. This presents a formidable technical challenge, but by combining a state-of-the-art motion capture suite with targets/obstacles moving under motion control in a custom-built facility, I will use system identification techniques to unambiguously identify the guidance and control laws underpinning perching, pursuit, obstacle avoidance, and gap negotiation in birds. More than this, I will identify the precise motion cues to which they attend, settling longstanding questions on the extent to which guidance emerges from simple algorithmic rules versus state feedback and estimation, with wider implications for our understanding of avian perception. This work will break new ground in all directions, testing applied insights in the same facility, and so leading the world in drawing the study of birds and aircraft together under one roof.

Mots-clés : vision,guidance,control,flight dynamics,bird flight,biomechanics,wing morphing
Projet ERC : bloodANDbone (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Karlsruhe Institute of Technology — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : KIT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 144115.46 €

Blood and bone are closely intertwined. Their intrinsic regenerative capacities are disturbed in many hematological and musculoskeletal diseases. Re-establishing the regenerative potential is the key to cure these diseases by regenerative medicine. Multipotent stem cells of both tissues – hematopoietic stem cells (HSCs) for blood and mesenchymal stem/stromal (MSCs) for bone – are the basis for their regenerative capacity. While it is well established that HSCs are influenced by the bone marrow in their natural environment including MSCs and their progeny, surprisingly little attention has been paid to the reciprocal relationship. The hypothesis of the current proposal is that only when taking both tissues and their mutual crosstalk into account, we will be able to understand how the regenerative potential of blood and bone is impaired in disease and how it can be re-established with novel treatment strategies. For this purpose we need to understand the early events of disease onset and progression. Due to the limitations of such studies in human beings and animals, I propose to develop human in vitro models of healthy bone marrow, which can be induced to develop hematological and musculoskeletal diseases with high incidence, namely leukemia, multiple myeloma and bone metastasis. Previously my team and I developed a simplified bone marrow analog that bases on macroporous, cell-laden biomaterials with tunable physical, biochemical and biological properties. This versatility will enable us to create biomimetic human in vitro models of the human bone marrow in health and disease, which are ground-breaking in their applicability to investigate how the regenerative balance of bone marrow is maintained in health and disturbed in the different kinds of diseases – a prerequisite to develop novel regenerative treatments – as well as their scalability and thus suitability as in vitro test systems for screening of novel drugs or treatments.
Projet ERC : AngioGenesHD (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Ministry of Health — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1481375.0 €

Blood and lymphatic vessels have been the subject of intense investigation due to their important role in cancer development and in cardiovascular diseases. The significant advance in the methods used to modify and analyse gene function have allowed us to obtain a much better understanding of the molecular mechanisms involved in the regulation of the biology of blood vessels. However, there are two key aspects that significantly diminish our capacity to understand the function of gene networks and their intersections in vivo. One is the long time that is usually required to generate a given double mutant vertebrate tissue, and the other is the lack of single-cell genetic and phenotypic resolution. We have recently performed an in vivo comparative transcriptome analysis of highly angiogenic endothelial cells experiencing different VEGF and Notch signalling levels. These are two of the most important molecular mechanisms required for the adequate differentiation, proliferation and sprouting of endothelial cells. Using the information generated from this analysis, the overall aim of the proposed project is to characterize the vascular function of some of the previously identified genes and determine how they functionally interact with these two signalling pathways. We propose to use novel inducible genetic tools that will allow us to generate a spatially and temporally regulated fluorescent cell mosaic matrix for quantitative analysis. This will enable us to analyse with unprecedented speed and resolution the function of several different genes simultaneously, during vascular development, homeostasis or associated diseases. Understanding the genetic epistatic interactions that control the differentiation and behaviour of endothelial cells, in different contexts, and with high cellular definition, has the potential to unveil new mechanisms with high biological and therapeutic relevance.

Mots-clés : angiogenesis,vascular biology,notch,vegf,development
Projet ERC : StemNicheOnWaveCrest (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1594500.0 €

Blood cells are produced in the bone marrow, which contains two distinct adult stem cell types: haematopoietic stem cells (HSCs), that generate all blood and immune cells, and mesenchymal stem cells (MSCs), thought to form the skeleton. HSCs traffic between bone marrow and circulation, what allows for life-saving clinical transplantation. Our previous work has shown that HSC numbers in blood are regulated by the central pacemaker in the brain, which reaches bone marrow nestin+ MSCs through the nerves. Contrarily to what it was believed, our recent data suggest that HSC-niche MSCs are different from those that form the skeleton and share instead a common origin with peripheral nerves and supporting glial cells. Thus, tight regulation of the bone marrow stem-cell niche in vertebrates might build upon developmental relationships of its cellular components. Moreover, we have shown that damage to this regulatory network is essential for the manifestation of myeloproliferative neoplasms, diseases that were previously thought to be driven solely by mutated HSCs. Also, JAK inhibitors (blocking the most frequent HSC mutation found in myeloproliferative neoplasms) cannot eradicate leukaemia stem cells. Our recent data has uncovered a selective regulation of normal and leukaemic haematopoietic progenitor maintenance, survival and division by sex hormones (oestrogens). These results might explain gender differences in blood cancer incidence and they also offer a new way of targeting leukaemia stem cells with clinically approved drugs. Nevertheless, we anticipate that the ideal future treatment of myeloproliferative diseases should target both leukaemia stem cells and their microenvironment. We have shown that protection or rescue of the niche is able to control the expansion of mutated cells. We aim to study this novel neuroendocrine regulation of bone marrow stem cells that will potentially fructify in new therapies for incurable myeloproliferative diseases.

Mots-clés : myeloproliferative diseases,chemotherapy,haematopoietic stem cell niche,mesenchymal stem cells,sympathetic nervous system,oestrogens
Projet ERC : MALART (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Leibniz Association — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LG
Type d'entité : Recherche
Financement ERC de l'entité : 2388242.5 €

Blood stages of the protozoan parasite Plasmodium falciparum are responsible for malaria, a disease that kills more than 400'000 people annually. During its development in red blood cells the parasite internalises a large part of the host cell cytosol (hemoglobin) in an endocytic process and digests it in its food vacuole. We recently identified a critical connection of this hemoglobin endocytosis with resistance of the parasite to the current frontline drug Artemisinin, revealing the mechanism of resistance. Artemisinin is activated by hemoglobin degradation products and we found that Artemisinin resistant parasite endocytose less. Using a toolbox of recently established approaches to carry out functional studies in malaria parasites, we identified an entire series of proteins involved in endocytosis that are involved in resistance to Artemisinin. This included Kelch13, the molecular marker of Artemisinin resistance in field samples. This provides us with a unique opportunity (i) to elucidate how these molecules orchestrate endocytosis, a prominent essential process in these parasites that so far is not understood on a molecular level, (ii) to specifically understand the role of Kelch13 in this process and in resistance, and (iii) to elucidate the reason for the fitness cost that is associated with Artemisinin resistance and the compensatory mechanisms the parasite uses to mitigate them. We expect this research program to not only elucidate so far elusive key aspects of the cell biology of this important parasite, but also to identify critical constraints of Artemisinin resistant parasites and possible ways to circumvent ART resistance.