Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
CRISPR Gene Correction for Severe Combined Immunodeficiency Caused by Mutations in Recombination-activating gene 1 and 2 (RAG1 and RAG2) (CRISS)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Prevention, Diagnosis and Treatment of Human Diseases
Panel description: Medical technologies and tools for prevention, diagnosis and treatment of human diseases, therapeutic approaches and interventions, pharmacology, preventative medicine, epidemiology and public health, digital medicine
Countries involved: Israel
Call: ERC Starting Grant (ERC-2017-STG, 2017)
Start date: 2017-10-01
End date: 2023-09-30
Duration (months): 72.0
Total project cost (EUR): 1372839.0
EU funding (EUR): 1372839.0
Participants: 1
Project status: SIGNED

The severe combined immunodeficiencies (SCIDs) are a set of life threatening genetic diseases in which patients are born with mutations in single genes and are unable to develop functional immune systems. While allogeneic bone marrow transplantation can be curative for these diseases, there remain significant limitations to this approach. Gene therapy using viral vectors containing a corrective transgene is being developed for some of these disorders, most successfully for ADA-SCID. However, for other SCID disorders, such as those caused by genetic mutations in RAG1 and RAG2, the transgene needs to be expressed in a precise, developmental and lineage specific manner to achieve functional gene correction and to avoid the risks of cellular transformation. In contrast to using viral vectors to deliver transgenes in an uncontrolled fashion, we are working towards using genome editing by homologous recombination (HR) to correct the disease causing mutation by precisely modifying the genome. We have shown that by using clustered, regularly interspaced, short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9) system we can stimulate genome editing by HR at frequencies that should be therapeutically beneficial (>10%) in hematopoietic stem and progenitor cells (HSPCs). The overall focus of the proposal is to translate our basic science studies to use in RAG-SCID patient-derived HSPCs in methodical, careful and pre-clinically relevant fashion. The fundamental approach is to develop a highly active functional genome editing system using CRISPR-Cas9 for RAG-SCIDs and complete pre-clinical efficacy and safety studies to show the approach has a clear path towards future clinical trials. Our goal with this proposal is to develop the next wave of curative therapies for SCIDs and other hematopoietic disorders using genome editing.

Keywords: genome editing,crispr,precision medicine,homologous recombination,dna repair,severe combined immunodeficiency
Eight millennia of changes in domestic plants and animals: understanding local adaptation under socio-economic and climatic fluctuations (DEMETER)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: The study of the human past
Panel description: Archaeology, history and memory
Countries involved: France
Call: ERC Starting Grant (ERC-2019-STG, 2019)
Start date: 2020-03-01
End date: 2025-02-28
Duration (months): 60.0
Total project cost (EUR): 1447800.0
EU funding (EUR): 1447800.0
Participants: 1
Project status: SIGNED

The domestication of plants and animals marks a major transition in human history and is a key element in the development of modern societies. Local and traditional domestic breeds and varieties are the result of millennia of selection of landraces by farmers. However, we are now experiencing a major crisis with a drastic loss in the diversity of food production systems and the progressive disappearance of traditional practices. The local knowledge and culture of farmers are under threat, as well as the diversity of harvested species, varieties and breeds. In this context, DEMETER’s objective is to trace how societies influenced crop and breed evolution under different farming and environmental regimes, and socio-economic contexts since the onset of agriculture. More specifically, DEMETER aims at identifying: 1) how and why the diversity of domestic forms evolved and led to the large number of breeds and varieties that exist today, and 2) how this diversity allowed societies to adapt to the environmental and socio-economic changes that occurred repeatedly since the onset of agriculture. DEMETER aims at studying the evolution, from the Neolithic until the present of a selection animal and plant models: pigs, sheep, goats and barley, in a given region, the Northwestern Occidental Mediterranean basin, i.e. outside their primary ‘domestication centre’. DEMETER will be based on an unprecedented and unconventional combination of approaches, including phenomics (through geometric morphometrics), databasing, zooarchaeology, archaeobotany, climate modelling, palaeoproteins (ZooMs) and statistical analyses, implemented to analyse 10,000 domestic specimens (i.e. mammal teeth and barley grains). DEMETER will produce an unprecedented regional synthesis of the relationships between humans and domesticates over the last 8 millennia in a new way and at a fine-scale resolution never envisioned before.

Keywords: domestication,husbandry practices,farming,bioarchaelogy
Regional disparities in cause-specific mortality in Europe: the role of local context and national health policies (REDIM)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: The Social World and Its Diversity
Panel description: Sociology, social psychology, social anthropology, education sciences, communication studies
Countries involved: Germany
Call: ERC Starting Grant (ERC-2019-STG, 2019)
Start date: 2020-08-01
End date: 2025-07-31
Duration (months): 60.0
Total project cost (EUR): 1423858.0
EU funding (EUR): 1423858.0
Participants: 1
Project status: SIGNED

Current socio-epidemiologic theories often perceive mortality (health) inequalities as a given and largely ignore the fundamental questions concerning their origin. Furthermore, the majority of prior studies on international differences in mortality have focused on cross-country differences without taking into account substantial regional variation within national populations. REDIM goes beyond the state of the art through performing a large-scale systematic investigation of the reasons for persisting and emerging spatial disparities in mortality across European countries. The scientific output of the project is crucial for developing and coordinating health policies aimed at reducing geographical inequalities in mortality across and within European countries. The project intends to quantify the degree of convergence/divergence in cause-specific mortality that occurs between subnational entities in Europe, and to identify determinants of these changes. REDIM focuses on two specific research questions: 1) How does the process of the general mortality decline diffuse across space, and what causes of death contribute most to this diffusion? 2) To what extent do national borders determine health borders? REDIM will tackle these research questions through analysing cause-specific mortality patterns and trends at NUTS-3 and NUTS-2 levels across 19 European countries. Mortality indicators will be interpreted in conjunction with contextual variables capturing the effects of local context and national health policies. The proposed research agenda is highly relevant to the context of the integration process within the European Union which strives to enhance coordination of policies to promote more equal access to all benefits and assets in society including health. Apart from expected ground-breaking scientific output, REDIM will provide advanced tools for evaluating the effectiveness of policies within the framework of the European Spatial Development Perspective.
DEVELOPING NATIONAL SCHEMES FOR ENERGY EFFICIENCY IN SMES (DEESME)

Framework: Horizon 2020 — Societal Challenges
Programme: Secure, clean and efficient energy
Theme: Reducing energy consumption and carbon foorpint by smart and sustainable use
Action type: Coordination and support actions
Countries involved: Italy,Germany,Germany,Italy,Bulgaria,Poland,Belgium,Netherlands
Call: Capacity building programmes to support implementation of energy audits (H2020-LC-SC3-EE-2019, 2019)
Start date: 2020-09-01
End date: 2023-12-31
Duration (months): 40.0
Total project cost (EUR): 1998686.25
EU funding (EUR): 1998686.25
Participants: 9
Project status: SIGNED

Unlike the EU Emissions Trading Scheme and large companies, SMEs have less technical human and financial resources to improve their energy efficiency. Barriers have been deeply investigated including lack of awareness, low capital and difficulty to access financing, doubts around actual saving potential and the lack of technical human resources. So, national schemes are finalized to provide them with technical resources such as methodologies, best practices, technologies inventories and subsidies. Some of the schemes introduce mandatory actions (energy analysis) to obtain such subsidies. Nevertheless, national policy schemes have failed to some extent to convince SMEs that the energy audit is something more than a “bureaucratic fulfilment” to obtain a contribution and to push also large companies to take the step from the analysis to the investment. To overcome that, DEESME aims at a) Enabling companies to manage the energy transition by taking profit of multiple benefits and energy management approaches, b) Supporting the development and the implementation of EU policies on energy efficiency in the framework of art. 8 of EED beyond the project by providing national authorities with guidelines proposals and recommendations on how to strengthen the national schemes and c) Enhancing the adoption of the DEESME approach by National Authorities beyond the project timeline through the implementation of institutionalization activities. DEESME will target primarily National Authorities to address their needs from the incumbent policies and to make them aware of the resources available to empower their schemes under art. 8 using the multiple benefits approach. Moreover, it will also target SMEs to assist them to develop and test the technical DEESME solutions by organising information and training initiatives, realising energy audit and implementing energy management systems starting from international standard and adding the multiple benefits energy efficiency approach.

Keywords: energy audits,policies
Engineering antibodies in B cells using endogenous AID activity (AutoEngineering)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Immunity, Infection and Immunotherapy
Panel description: The immune system, related disorders and their mechanisms, biology of infectious agents and infection, biological basis of prevention and treatment of infectious diseases, innovative immunological tools and approaches, including therapies
Countries involved: Germany
Call: ERC STARTING GRANTS (ERC-2020-STG, 2020)
Start date: 2021-07-01
End date: 2026-06-30
Duration (months): 60.0
Total project cost (EUR): 1489500.0
EU funding (EUR): 1489500.0
Participants: 1
Project status: SIGNED

The AutoEngineering project aims to develop an innovative strategy for B cell engineering by exploiting natural DNA breaks to generate antibodies that surpass common reactivity profiles. The project is based on our surprising finding that in B cells endogenous AID (activation-induced cytidine deaminase) activity can lead to the insertion of a pathogen receptor resulting in broadly reactive antibodies. To unravel this new mechanism of diversification, my laboratory established and developed new methodologies to identify insert-containing antibodies in genomic DNA, mRNA, proteins and cells. We found that insertions in antibody transcripts derive from distant genes, occur across individuals and are inducible in vitro, and we have preliminary evidence that in vitro activation of AID enables integration of a nucleofected DNA substrate. Avoiding exogenous nucleases, this project aims at developing efficient and safe engineering of B cells to produce antibodies by design. Aim 1. By screening for genomic insertions in antibody genes of healthy donors, DNA-repair deficient patients, and manipulated in vitro B cell cultures, we will gain insights into the mechanism of insertion and define biomarkers of DNA repair. Aim 2. The knowledge gained will be used to optimize substrate design and insert integration, while minimizing the potential for off-target integration. We will also explore the possibility to guide AID to target sites using RNAs, and design substrates that allow efficient splicing of an inserted exon. Aim 3. To gain breadth on pathogen recognition and to circumvent the limitation of the heterodimeric antibody binding site, we will use the above approach to engineer B cells to produce antibodies containing receptors for HIV (CD4) and HCV (CD81). Insertion of slim receptor-domains with precise targeting of crucial sites may generate B cells with exceptional potency to reduce the risk for escape mutants, thereby paving a way for artificial immunity.

Keywords: b cell,human antibodies,cell engineering,antibody diversity,broadly reactive antibodies,infectious diseases,dna repair
PROjecTing sEa-level rise : from iCe sheets to local implicaTions (PROTECT)

Framework: Horizon 2020 — Societal Challenges
Programme: Climate action, environment,  resource efficiency and raw materials
Theme: Fighting and adapting to climate change
Action type: Research and Innovation actions
Countries involved: Germany,Germany,Germany,Germany,Switzerland,Belgium,Belgium,Norway,France,France,France,Netherlands,Netherlands,Maldives,Denmark,United Kingdom,United Kingdom,United Kingdom,United Kingdom,United Kingdom,United Kingdom,Greenland,Denmark,United Kingdom
Call: The changing cryosphere: uncertainties, risks and opportunities (H2020-LC-CLA-2019-2, 2019)
Start date: 2020-09-01
End date: 2024-08-31
Duration (months): 48.0
Total project cost (EUR): 9996661.45
EU funding (EUR): 9996661.45
Participants: 28
Project status: SIGNED

Sea-level rise (SLR) is one of the most damaging impacts of climate change, threatening the economy, ecology, and entire existence of coastal regions worldwide. Global-mean sea level has risen by ~8 cm since 1992, with land ice loss and ocean thermal expansion contributing equally. However, the land ice contribution is accelerating, and future SLR is set to become dominated by the highly uncertain behaviour of the Antarctic and Greenland ice sheets. The potential for rapid collapse of these ice sheets, which may already be underway, has made policymakers painfully aware of humanity’s vulnerability to ice-sheet change. PROTECT will push SLR projections beyond the state-of-the-art and have a long-standing scientific and societal impact by (i) significantly improving our understanding and model representation of ice-sheet processes, (ii) providing a step change in modelling the interactions and feedbacks between atmosphere, ocean, and ice sheets, (iii) improving the robustness of the resulting SLR projections, with a clear propagation of uncertainties from global to regional scales, (iv) assessing the societal implications of high-end ice-sheet SLR over decades to centuries, (v) developing and mentoring the next generation of sea-level scientists. Recognizing that developing climate services for coastal adaptation is an iterative process, PROTECT will engage stakeholder knowledge from key EU states vulnerable to SLR, as well as communities from low-lying islands and the Arctic. PROTECT unifies world-leading European experts in cryospheric and climate science, sea-level change, and coastal and societal impacts. This highly interdisciplinary consortium will cover, for the first time, all relevant spatial and temporal scales governing SLR from land ice. PROTECT will provide a solid evidence base needed to implement measures addressing the Sustainable Development Goals (SDGs) of the United Nations, the European Union Adaptation Strategy, and the UNFCCC Paris Agreement.

Keywords: cryosphere antarctica,greenland,ice caps and glaciers,global,regional slr projections and implications mitigation,adaptation,ice sheet,ocean,atmosphere and climate modeling,earth observation
Plasma epigenomics: A new liquid biopsy paradigm (cfChIP)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: Prevention, Diagnosis and Treatment of Human Diseases
Panel description: Medical technologies and tools for prevention, diagnosis and treatment of human diseases, therapeutic approaches and interventions, pharmacology, preventative medicine, epidemiology and public health, digital medicine
Countries involved: Israel
Call: ERC ADVANCED GRANT (ERC-2020-ADG, 2020)
Start date: 2021-08-01
End date: 2026-07-31
Duration (months): 60.0
Total project cost (EUR): 2962500.0
EU funding (EUR): 2962500.0
Participants: 1
Project status: SIGNED

Genomic DNA is packaged by histone proteins that carry a multitude of post-translational modifications, which reflect cellular transcriptional states. When cells die, fragmented chromatin retaining histone modifications is released to the circulation. Recently, we pioneered chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin marks followed by sequencing (cfChIP-seq). Our results show that cfChIP-seq provides multidimensional epigenetic information and that the plasma epigenome contains rich information about the identity and the transcriptional state of the originating cells. Liquid biopsies already entered the clinical practice, yet current methodologies use them to assess genetic information. Our breakthrough methodology opens an unprecedented opportunity to delineate the transcriptional state of specific cell types and different pathologic states. Here we aim to translate plasma epigenomic information into medically relevant findings. The challenge is recovering the states of the cells represented in the circulation and relate these to pathological processes. Our working hypothesis is that this task is attainable by probabilistic modeling exploiting knowledge about epigenomics and transcription programs in health and disease. In this project we will assay plasma samples from multiple patient and donor cohorts to characterize the relation between tissue gene expression and circulating chromatin profiles, to recover the immune system status and chart how it changes with disease progression and response to treatment, and to monitor transplant patients for early detection of rejection. Our extensive preliminary data, our expertise in probabilistic modeling and genomics and our collaborators’ access to relevant patient cohorts support the projects’ feasibility. Plasma epigenomics will open a new non-invasive window into tissue dynamics in living humans, beyond current liquid biopsy technologies, with far-reaching medical implications.

Keywords: liquid biopsy,cell free nucleosomes,cell free chromatin,diagnosis of disease,monitoring treatment efficacy,transplant rejection
Statistical multi-Omics UNDerstanding of Patient Samples (SOUND)

Framework: Horizon 2020 — Societal Challenges
Programme: Health, demographic change and wellbeing
Theme: Health care provision and integrated care
Action type: Research and Innovation actions
Countries involved: Germany,Germany,Switzerland,United States,Netherlands,United Kingdom,Portugal
Call: Advancing bioinformatics to meet biomedical and clinical needs (H2020-PHC-2014-two-stage, 2014)
Start date: 2015-09-01
End date: 2018-08-31
Duration (months): 36.0
Total project cost (EUR): 3656977.5
EU funding (EUR): 2953062.5
Participants: 13
Project status: CLOSED

Bioinformatic analysis is the biggest bottleneck in many genomic medicine projects. Our objective is to enable researchers to dramatically increase statistically informed use of personal multi-omic data in medicine. Soon, multiple types of omic technologies will be applied to 100,000s of patient-derived samples, with the three-stage goal of better understanding disease biology, discovery of new interventions, and personalizing the choice of treatment options. Our interdisciplinary team of biostatisticians, bioinformaticians, software developers and physician-scientists will address the analysis bottleneck with statistically and computationally sound methods. The SOUND consortium will (i) develop widely used and excellent bioinformatic and statistical methods and open source software for common but challenging tasks, including data pre-processing, data integration, statistical inference, visual presentation, and publication-quality reporting; (ii) introduce novel approaches to ground breaking multi-omics applications in oncology and medical genetics; (iii) develop interoperable data structures and software interfaces that enable seamless combination of tools; (iv) support a collaborative international academic and industry developer community; (v) enable rapid development and execution of high-quality software; (vi) lower the barrier to entry into this transdisciplinary field by providing simple, robust, easy-to-use solutions; and (vii) develop a training programme with regular courses and comprehensive online tutorials. Our aim is to create the de facto standard toolkit used in every clinical research lab for statistically informed analysis of personal multi-omic data. SOUND will increase research and innovation opportunities by reducing barriers of entry to genomic medicine across academic, healthcare and commercial sectors by translating in a rapid and efficient manner complex and innovative analytical approaches into modular, interoperable, reusable applications.

Keywords: statistics,personalised medicine,multi omics,cell based screening,drug screening,cancer,drug sensitivity,prediction,collaborative software development,software interoperability,bioconductor