Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : AcetyLys (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Ben-Gurion University of the Negev — Pays : Israël — Rôle : PI
Acronyme de l'entité : BGU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499375.0 €

Synthetic biology is an emerging discipline that offers powerful tools to control and manipulate fundamental processes in living matter. We propose to develop and apply such tools to modify the genetic code of cultured mammalian cells and bacteria with the aim to study the role of lysine acetylation in the regulation of metabolism and in cancer development. Thousands of lysine acetylation sites were recently discovered on non-histone proteins, suggesting that acetylation is a widespread and evolutionarily conserved post translational modification, similar in scope to phosphorylation and ubiquitination. Specifically, it has been found that most of the enzymes of metabolic processes—including glycolysis—are acetylated, implying that acetylation is key regulator of cellular metabolism in general and in glycolysis in particular. The regulation of metabolic pathways is of particular importance to cancer research, as misregulation of metabolic pathways, especially upregulation of glycolysis, is common to most transformed cells and is now considered a new hallmark of cancer. These data raise an immediate question: what is the role of acetylation in the regulation of glycolysis and in the metabolic reprogramming of cancer cells? While current methods rely on mutational analyses, we will genetically encode the incorporation of acetylated lysine and directly measure the functional role of each acetylation site in cancerous and non-cancerous cell lines. Using this methodology, we will study the structural and functional implications of all the acetylation sites in glycolytic enzymes. We will also decipher the mechanism by which acetylation is regulated by deacetylases and answer a long standing question – how 18 deacetylases recognise their substrates among thousands of acetylated proteins? The developed methodologies can be applied to a wide range of protein families known to be acetylated, thereby making this study relevant to diverse research fields.

Mots-clés : acetylation,genetic code expansion,glycolysis,metabolism,photo labile protecting groups,organic synthesis,directed evolution,enzyme substrate recognition
Projet ERC : VDJtargeting (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496875.0 €

T cell engineering has shown clinical success mainly in haematological cancers, but scaling up is challenging due to reliance on ex vivo manipulations. In addition, B cell engineering has not shown therapeutic efficacy to date. Here, we propose a novel immunotherapy approach, allowing safe and efficient engineering of B cells and T cells, both ex vivo and in vivo. We will use adeno associated vectors (AAV) to integrate chimeric antigen receptor (CAR) or T cell receptor (TCR) genes into loci coding TCR chains and to integrate antibody (Ab) genes into loci coding Ab chains. Previously, we used AAV facilitated gene targeting in vivo to ameliorate genetic diseases in mice. For lymphocytes we develop “VDJ targeting”: A promoterless receptor/Ab gene flanked by recognition signal sequences (RSS) will be inserted into the endogenous locus by the recombination activating gene (RAG) complex during V(D)J recombination. Only developing lymphocytes, expressing RAG, will incorporate the receptor/Ab gene, which will thus be expressed in potent naïve cells from the strong endogenous promoter. Targeted developing cells are subjected to negative selection, thus reducing risk of adverse autoimmunity. Lack of promoter reduces spurious expression and oncogenic risk upon rare off-target integration. Targeting endogenous loci may allow allelic exclusion. In B cells it may allow utilizing the endogenous constant region to express a B cell receptor and, upon activation, a secreted Ab. Activation may be accompanied by proliferation and affinity maturation, including somatic hypermutation and class switching, to allow a potent immune response, memory retention and diminished antigenic escape. Where controlled autoimmunity is desired, we will engineer B cells to inducibly secret an auto-Ab. We will demonstrate efficacy in cancer and autoimmune disease models implanted with lymphocytes that we engineered while ex vivo differentiated and in mice injected with vectors for in vivo VDJ targeting.

Mots-clés : gene therapy,immunotherapy,gene editing,cancer,autoimmune
Projet ERC : FunDiT (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Czech Academy of Sciences — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : AVČR;CAS
Type d'entité : Recherche
Financement ERC de l'entité : 1725000.0 €

T cells have a central role in most adaptive immune responses, including immunity to infection, cancer, and autoimmunity. Increasing evidence shows that even resting steady-state T cells form many different subsets with unique functions. Variable level of self-reactivity and previous antigenic exposure are most likely two major determinants of the T-cell diversity. However, the number, identity, and biological function of steady-state T-cell subsets are still very incompletely understood. Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of T-cell fate decisions. We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The FunDiT project uses a set of novel tools to systematically identify steady-state CD8+ T cell subsets and characterize their biological roles. The project has three complementary objectives. (1) Identification of CD8+ T cell subsets. We will identify subsets based on single cell gene expression profiling. We will determine the role of self and foreign antigens in the formation of these subsets and match corresponding subsets between mice and humans. (2) Role of particular subsets in the immune response. We will compare antigenic responses of particular subsets using our novel model allowing inducible expression of a defined TCR. The activity of T-cell subsets in three disease models (infection, cancer, autoimmunity) will be characterized. (3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to identify receptors and signaling molecules involved in the signaling by ligands from TNF and B7 families in T cells. The results will provide understanding of the adaptive immunity in particular disease context and resolve long-standing questions concerning the roles of T-cell diversity in protective immunity and tolerance to healthy tissues and tumors.

Mots-clés : t cell heterogeneity
Projet ERC : TB-EPF (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Instituut voor Tropische Geneeskunde — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ITM;ITG;IMT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 69521.75 €

TB is transmitted via person-to-person aerosols. Recent studies suggests that in TB endemic areas up to 70% of transmission events take place outside the household in public places. Moreover, TB transmission is unequally spatially distributed and occurs in transmission hotspot areas. Mathematical models consequently demonstrated that identifying hotspots and blocking within-hotspot-transmission through targeted public health interventions will be the most efficient way of lowering the TB burden. In the present PoC proposal we aim to complement the population-based Enhanced-Case-Finding intervention tested in the INTERRUPTB study, with a spatially more targeted “Enhanced-Place-Finding” (EPF) approach to identify transmission hotspots in an unbiased fashion. Using traditional methods to find transmission hotspots can only be done retrospectively after years of data collection. Therefore we propose a novel EPF strategy to detect transmission hotspots in real-time using phone-tracking technology to establish a spatial map of aggregated TB patients movements. Within the ERC-funded INTERRUPTB study in The Gambia, we sequenced 2000 mycobacterial isolates, which allows us to establish a bacterial genetic transmission network. Within the PoC proposal, we seek to reconsent these patients to analyze their everyday movements using classical contact investigation complemented by phone tracking, to determine which public places have an increased risk of TB transmission. We aim to demonstrate that phone tracking of TB patients can be a cheap, easy, and, most importantly, prospective TB transmission hotspots identification tool, no longer requiring molecular epidemiological investigations. Such a finding can ultimately be developed into an app that warns national TB programs of early TB outbreaks, so that early public health measures like increased ventilation and active case finding can be initiated. This approach can furthermore be applied to other infectious diseases.

Mots-clés : tuberculosis transmission hotspots case finding phone tracking
Projet ERC : TB-EPF (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of London — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 31661.25 €

TB is transmitted via person-to-person aerosols. Recent studies suggests that in TB endemic areas up to 70% of transmission events take place outside the household in public places. Moreover, TB transmission is unequally spatially distributed and occurs in transmission hotspot areas. Mathematical models consequently demonstrated that identifying hotspots and blocking within-hotspot-transmission through targeted public health interventions will be the most efficient way of lowering the TB burden. In the present PoC proposal we aim to complement the population-based Enhanced-Case-Finding intervention tested in the INTERRUPTB study, with a spatially more targeted “Enhanced-Place-Finding” (EPF) approach to identify transmission hotspots in an unbiased fashion. Using traditional methods to find transmission hotspots can only be done retrospectively after years of data collection. Therefore we propose a novel EPF strategy to detect transmission hotspots in real-time using phone-tracking technology to establish a spatial map of aggregated TB patients movements. Within the ERC-funded INTERRUPTB study in The Gambia, we sequenced 2000 mycobacterial isolates, which allows us to establish a bacterial genetic transmission network. Within the PoC proposal, we seek to reconsent these patients to analyze their everyday movements using classical contact investigation complemented by phone tracking, to determine which public places have an increased risk of TB transmission. We aim to demonstrate that phone tracking of TB patients can be a cheap, easy, and, most importantly, prospective TB transmission hotspots identification tool, no longer requiring molecular epidemiological investigations. Such a finding can ultimately be developed into an app that warns national TB programs of early TB outbreaks, so that early public health measures like increased ventilation and active case finding can be initiated. This approach can furthermore be applied to other infectious diseases.

Mots-clés : tuberculosis transmission hotspots case finding phone tracking
Projet ERC : TEXTEVOLVE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 234933.75 €

TEXTEVOLVE will study the Targums. Targums are Jewish Aramaic paraphrases of the Hebrew Bible. They are important because they provide a unique insight into what Jews believed God was saying to them through their sacred texts at transformative moments in Jewish history, particularly the aftermath of the First Jewish-Roman War (66–74 CE). The state of the art in the study of the Targums is defined by 1) methodology, and 2) the primary sources that are available. TEXTEVOLVE will go beyond the state of the art in both areas. Methodology — We do not possess the author’s original copy of any Targum. Rather, in most cases we have multiple copies preserved in much later manuscripts, all of which differ one from another. Existing methodology aims to reconstruct the earliest possible form of the text. But changes made by later copyists also yield important insights into evolving Jewish culture, theology, and praxis. Therefore TEXTEVOLVE reframes the dominant research question in the field so that neither the importance of the original wording nor the significance of subsequent changes is neglected. It asks: How did the text of the Targums evolve over time and why? TEXTEVOLVE will develop a new methodology, called Evolutionary Philology, that is capable of addressing this core question. It will use techniques from evolutionary biology that have not previously been applied to texts to achieve this. This will have implications across disciplines that work with historical texts. Primary Sources — To ensure the most robust possible dataset, TEXTEVOLVE will expand the pool of primary sources available for analysis. TEXTEVOLVE will find Targum manuscripts that have been ‘lost’ in un-catalogued or poorly catalogued collections, and will analyse for the first time recently discovered manuscripts from the ‘European Genizah’. Since the available primary sources define the boundaries of any discipline, this is the second major way in which TEXTEVOLVE goes beyond the state of the art.

Mots-clés : jewish studies,manuscript studies,targum,aramaic
Projet ERC : SEEWHI (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Technical University of Denmark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

THE GOAL We will derive new and fundamental insight in the relation between nano-scale structure and the performance of 3rd generation solar cells, and determine how to apply this in large-scale processing. THE CHALLENGES We currently have a superficial understanding of the correlations between structure and performance of photovoltaic heterojunctions, based on studies of small-scale devices and model systems with characterization techniques that indirectly probe their internal structure. The real structures of optimized devices have never been “seen”, and in devices manufactured by large-scale processing, almost nothing is known about the formation of structures and interfaces. THE SCIENCE We will take a ground-breaking new approach by combining imaging techniques where state of the art is moving in time spans on the order of months, with ultrafast scattering experiments and modelling. The techniques include high resolution X-ray phase contrast and X-ray dark-field tomography, in situ small and wide angle X-ray scattering, resonant scattering and imaging and time resolved studies of charge transport and transfer. To relate our findings to device performance, we will establish full 3D models of charge generation and transport in nano-structured solar cells. THE FOCUS Solution cast solar cells is the only technology that promises fast and cheap industrial scaling, and it is consequently the focus of our efforts. They require a tight control of processing conditions to ensure that the proper nano-structure is formed in the photoactive layers, with optimal contacts to charge transport layers and interfaces. The prime contenders are non-toxic polymer and kesterite solar cells. THE IMPACT Our results may advance 3rd generation, solution-cast solar cells to meet the “unification challenge” where high efficiency, stability and cheap processing combines in a single technology, scalable to the level of gigawatts per day, thus becoming a centrepiece in global energy supply.

Mots-clés : solution cast solar cells,ultrahigh resolution imaging,ultrafast imaging of charge currents,modelling of charge generation and transport
Projet ERC : gRESONANT (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Oslo — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1443472.0 €

THE GRAND CHALLENGE: The “Holy Grail” of nuclear astrophysics is to understand the astrophysical processes responsible for the formation of the elements. A particularly challenging part is the description of the heavy-element nucleosynthesis. The only way to build the majority of these heavy nuclides is via neutron-capture processes. Unaccounted-for nuclear structure effects may drastically change these rates. MAIN HYPOTHESIS: Nuclear low-energy gamma-decay resonances at high excitation energies will enhance the astrophysical neutron-capture reaction rates. NOVEL APPROACH: This proposal is, for the first time, addressing the M1 scissors resonance in deformed, neutron-rich nuclei and superheavy elements. A new experimental technique will be developed to determine the electromagnetic nature of the unexpected upbend enhancement. Further, s-process branch points for the Re-Os cosmochronology will be studied for the first time with the Oslo method. OBJECTIVES: 1) Measure s-process branch point nuclei with the Oslo method 2) Radioactive-beam experiments for neutron-rich nuclei searching for the low-energy upbend and the M1 scissors resonance 3) Develop new experimental technique to identify the upbend’s electromagnetic nature 4) Superheavy-element experiments looking for the M1 scissors resonance POTENTIAL IMPACT IN THE RESEARCH FIELD: This proposal will trigger a new direction of research, as there are no data on the low-energy gamma resonances neither on neutron-rich nor superheavy nuclei. Their presence may have profound implications for the astrophysical neutron-capture rates. Developing a new experimental technique to determine the electromagnetic character of the upbend is crucial to distinguish between two competing explanations of this phenomenon. Unknown neutron-capture cross sections will be estimated with a much better precision than prior to this project, and lead to a major leap forward in the field of nuclear astrophysics.

Mots-clés : nuclear gamma decay resonances,gamma ray strength function,nuclear experiments,stable beam,radioactive beam experiments,neutron capture reactions,astrophysical reaction rates
Projet ERC : TILC (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Hôpital de la Timone Adulte — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 242500.0 €

TILC focuses on Innate Lymphoid Cells (ILCs). ILCs are a newly discovered type of lymphocyte, and their study opens up new perspectives for understanding and manipulating of immunity. ILCs include cytotoxic ILCs (NK cells) and helper-like ILCs (ILC1, ILC2 & ILC3). Studies of ILC2 cells have advanced considerably, but much remains unknown about the respective roles of NK, ILC1 and ILC3 cells. TILC aims to explore new frontiers in ILC biology, by focusing on these subsets of ILCs in mice and humans, through five specific aims. 1. NK cells, ILC1 & NCR+ILC3 are known to express NKp46 in humans and mice, but the nature of the NKp46 ligands remains unclear, limiting our understanding of the biology of these three major ILC subsets. We thus aim to identify the NKp46 ligands, building on our preliminary data showing that Complement Factor P (CFP, Properdin) is involved in NKp46 recognition, hence revealing an unprecedented mode of immune recognition. 2. We also aim to create new mouse models selectively targeting these ILC subsets in vivo. We will then use these models for dissecting out the selective roles of ILC subsets in two major immune functions: cancer surveillance and gut homeostasis. 3. In cancer, we will investigate the contribution of these cells to tumor editing. 4. In the intestine, we will focus on the homeostasis of the cecum and appendix. These organs were long considered to be vestiges of evolution, but our own recent findings and those of phylogenetic studies have challenged this notion. We thus aim to address the role of ILC subsets in the cecum/appendix, and determine whether these organs serve as a refuge for repopulation with commensals after dysbiosis. 5. Finally, we aim to identify patients with deficiencies in ILCs, to dissect the function of these cells in natura. From the molecular scale to that of patients, we believe that TILC will provide answers to some of the most pressing questions concerning the role and clinical potential of NKp46+ ILCs

Mots-clés : innate immunity,innate lymphoid cells,natural killer cells
Projet ERC : TRENSCRYBE (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Sorbonne Université — Pays : France — Rôle : Partner
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 50638.75 €

TRENSCRYBE proposes a groundbreaking concept for a quantum simulator (QS) of spin systems. QSs aim at an in-depth understanding of many-body physics, important for fundamental issues (quantum transport, phase transitions), but also for the development of engineered materials. A QS transcribes the system of interest into another with the same dynamics but with a fully controlled Hamitlonian parameter set. It provides a complete access to all the systems observables and allows the exploration of regimes, in which numerical simulations are difficult or impossible due to the huge size of the Hilbert space. QSs of spin systems are the focus of an intense activity, e.g. with trapped ions, superconducting devices, atoms in optical lattices or low-angular-momentum Rydberg atoms. I propose with TRENSCRYBE a disruptive QS using trapped circular Rydberg atoms. Their microwave spontaneous emission can be inhibited, extending their lifetime in the minute range. In contrast with ordinary Rydberg states, they can be trapped in optical lattices, allowing one to take full benefit from such exceptional lifetimes. I propose an innovative preparation method of ultra-cold defect-free chains with a few tens of atoms. The QS realizes a Nearest-Neighbor XXZ spin-1/2 Hamiltonian in a transverse field, the spin states being coded on circular levels. Its parameters are fully tunable by adjusting a static electric field and a microwave dressing applied on the atoms. I will first benchmark this QS by adiabatic evolutions through the phase diagram of a 1-D chain in a regime where numerical results are available. I will explore quenches through quantum phase transitions and the generation of defects in a regime where numerical or theoretical predictions are difficult. I will realize a first step towards 2-D arrays with spin ladders and explore their topological phases. The realization of TRENSCRYBE will open a whole realm of new possibilities for quantum simulation of spin systems.

Mots-clés : quantum simulator,ultracold rydberg atoms,spin chain