Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Rheuma Tolerance for Cure (RTCure)

Framework: Horizon 2020 — Societal Challenges
Programme: Health, demographic change and wellbeing
Theme: Public-private partnerships
Destination: Innovative Medicines Initiative 2
Action type: Research and Innovation actions
Partnership: IMI2 (Art-187)
Countries involved: Austria,Germany,Australia,Germany,Germany,Hungary,Belgium,Belgium,Switzerland,Belgium,Sweden,Netherlands,United States,United Kingdom,United Kingdom,United Kingdom,United Kingdom,United Kingdom,United Kingdom
Call: DEVELOPMENT OF IMMUNE TOLERANCE THERAPIES FOR THE TREATMENT OF RHEUMATIC DISEASES (H2020-JTI-IMI2-2016-09-two-stage, 2016)
Start date: 2017-09-01
End date: 2023-08-31
Duration (months): 72.0
Total project cost (EUR): 13511715.4
EU funding (EUR): 6000000.0
Participants: 20
Project status: SIGNED

In line with IMI2 goals for improved therapies and precision medicine, the aim of this proposal is to prevent and treat RA or its progression by inhibiting maturation/expansion of pathogenic autoimmune responses through immune tolerising treatments of subjects not only in early stages of joint inflammation (undifferentiated arthritis and early RA) but also in even earlier defined stages i.e. before onset of joint inflammation, when patients have arthralgia and/or bone loss, or sub-clinical stages of joint inflammation. Today, no drugs are approved for these early phases of RA development, where symptoms such as pain and fatigue cause major loss of life quality and where successful interference would prevent onset of disease. Thus, an important part of our work will be to achieve a better understanding of this as yet unexplored phase of disease. In the proposed project we will develop and validate new methods to identify individuals at high risk for RA, tools to monitor disease progress and expand and further develop cohorts suitable for these purposes. Furthermore we will validate and standardise methods to monitor immune tolerance to be used in clinical trials for tolerising therapies for RA. The aim is thus to interfere with the specific immune reactions that contribute to RA symptoms in such a way that a specific and long-lasting therapeutic effect (ultimately a cure) is accomplished for a major proportion of RA patients and prevention of diseases is accomplished in individuals at high risk for RA. Investigator-initiated as well as company-sponsored clinical trials in well stratified patient groups will be performed in collaboration with SMEs and/or contributing pharma companies and their immune effects studied using the same panel of biomarkers allowing for standardisation across protocols. Our ambition is also to disseminate our experiences from RA to other rheumatic and other immune-mediated diseases.

Keywords: tolerance,rheumatoid arthritis
Design of the European mobile network operator for research (EuWireless)

Framework: Horizon 2020 — Excellent Science
Programme: Research Infrastructures
Theme: Research infrastructures
Destination: Development and infrastructures
Action type: Research and Innovation actions
Countries involved: Spain,Finland,Belgium,Poland,Denmark
Call: Design Studies (H2020-INFRADEV-2017-1, 2017)
Start date: 2018-01-01
End date: 2020-03-31
Duration (months): 27.0
Total project cost (EUR): 2047937.5
EU funding (EUR): 2047937.5
Participants: 6
Project status: CLOSED

The objective of EuWireless proposal is to develop the design of the first pan-European infrastructure to support research in mobile communication networks using regulated spectrum, with the goal of contributing to keep Europe’s leadership in mobile communication technologies. The output of the project will be a complete design report addressing the pan-European operator, the regulatory aspects, the business model, the technical solutions and the roadmap for implementation of the proposed infrastructure, as well as prototypes that confirm its feasibility.

Keywords: mobile networks,testbeds,experimental facilities
Just-in-time Self-Verification of Autonomous Systems (justITSELF)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Systems and communication engineering
Panel description: Electrical, electronic, communication, optical and systems engineering
Countries involved: Germany
Call: ERC Consolidator Grant (ERC-2018-COG, 2018)
Start date: 2019-07-01
End date: 2024-06-30
Duration (months): 60.0
Total project cost (EUR): 1999075.0
EU funding (EUR): 1999075.0
Participants: 1
Project status: SIGNED

Engineers and computer scientists are currently developing autonomous systems whose entire set of behaviors in future, untested situations is unknown: How can a designer foresee all situations that an autonomous road vehicle, a robot in a human environment, an agricultural robot, or an unmanned aerial vehicle will face? Keeping in mind that all these examples are safety-critical, it is irresponsible to deploy such systems without testing all possible situations---this, however, seems impossible since even the most important possible situations are unmanageably many. I propose a paradigm shift that will make it possible to guarantee safety in unforeseeable situations: Instead of verifying the correctness of a system before deployment, I propose just-in-time verification, a new, to-be-developed verification paradigm where a system continuously checks the correctness of its next action by itself in its current environment (and only in it) in a just-in-time manner. Since future autonomous systems will have a tight interconnection of discrete computing and continuous physical elements, also known as cyber-physical systems, I will develop just-in-time verification for this system class. In order to prove correct behavior of cyber-physical systems, I will develop new formal verification techniques that efficiently compute possible future behaviors---subject to uncertain initial states, inputs, and parameters---within a small time horizon. Just-in-time verification will substantially cut development costs, increase the autonomy of systems (e.g., the range of deployment of automated driving systems), and reduce or even eliminate certain liability claims. The results will be implemented in an open-source software framework and will be primarily demonstrated for automated driving. Successful development of just-in-time verification techniques is yet more challenging than offline verification of autonomous systems, but expected to bring even greater rewards.

Keywords: reachability analysis,formal verification,autonomous systems,hybrid systems,conformance checking
Electron Microscopy gene reporters based on bioengineered encapsulin nanocompartments (EMcapsulins)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Biotechnology and Biosystems Engineering
Panel description: Biotechnology using all organisms, biotechnology for environment and food applications, applied plant and animal sciences, bioengineering and synthetic biology, biomass and biofuels, biohazards
Countries involved: Germany,Germany
Call: ERC Consolidator Grant (ERC-2019-COG, 2019)
Start date: 2020-09-01
End date: 2025-08-31
Duration (months): 60.0
Total project cost (EUR): 1997549.0
EU funding (EUR): 1772549.0
Participants: 2
Project status: SIGNED

The biological engineering project EMcapsulins will create the first suite of multiplexed genetic reporters for electron microscopy (EM) to augment today’s merely structural brain circuit diagrams (connectomes) with crucial information on neuronal type and activation history. My team will generate this new toolbox based on genetically encoded nanocompartments of the prokaryotic ‘encapsulin’ family that we have recently shown to enable genetically controlled compartmentalization of multicomponent processes in mammalian cells. By encapsulating metal-organizing cargo proteins in the lumen of the semi-permeable encapsulin nanospheres, they serve as fully genetic EM gene reporters (EMcapsulins) that provide robust and spatially precise contrast by conventional EM in mammalian cells. To enable geometric multiplexing in EM in analogy to multi-color light microscopy, we will explore the large geometrical feature space of EMcapsulins to establish three core Functionalities: ① different shell structures and diameters, ② modular and tunable shell functionalizations, and ③ multiplexed and triggered cargo loading. We will combine these Functionalities to produce geometrically multiplexed EMcapsulin markers of neuronal identity in serial EM (Application ❶). We will also engineer EMcapsulin reporters for activity-dependent gene expression, calcium signaling, and synaptic activity that can ‘write’ geometrically encoded records of neuronal activation history into EM connectomics data (Application ❷). These ‘multi-color’ and modular EMcapsulin markers and reporters deliver the missing bridging technology between time-resolved light microscopy measurements of neuronal activation dynamics and structural EM connectomics data. EMcapsulin technology will convert structural to functional EM connectomes to enable a systematic analysis of how brains write molecular signaling dynamics into structural patterns to store information for later retrieval.

Keywords: biological engineering,synthetic biology,gene reporters,protein design,nanocompartments,iron biomineralization,molecular imaging,calcium imaging,electron microscopy,neuronal activity,connectomics
Modelling undiagnosed muscular dystrophies using patients's stem cells (MUMDUPSC)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Reintegration panel
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: France
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2021-09-15
End date: 2023-09-14
Duration (months): 24.0
Total project cost (EUR): 196707.84
EU funding (EUR): 196707.84
Participants: 1
Project status: SIGNED

Neuromuscular Diseases (NMDs), affecting both children and adults with a prevalence of 1 in a 1000 people, form a large and heterogeneous group of genetic diseases causing progressive degeneration of skeletal muscles. Most NMDs result in chronic long-term disability imposing a significant burden on patients, families and public health care. In many cases, patients die prematurely from respiratory, and in some cases cardiac, muscle impairment. There are more than 200 NMDs, including over 30 types of Muscular Dystrophy (MD) which results from the mutation of genes controlling muscle functions and structures. The classification of MDs is not fixed but evolves with the constant discovery of new genes/mutations responsible for these diseases. Despite more than 40 genes involved in MDs have already been identified many genes are still to be discovered. In Europe, thousand patients with MD are currently without molecular diagnosis. Delayed or inaccurate diagnoses postpone the adequate care and may have irreversible consequences for the patients. MUMDUPSC aims combining descriptive clinical diagnosis, genomics and disease modelling from patients’ induced Pluripotent Stem Cells (hiPSC) to identify both molecular mechanisms and genetic mutations underlying undiagnosed muscular dystrophies (UMDs). Specifically, I propose to generate hiPSC from selected UMD patients and investigate their transcription profile during skeletal muscle differentiation compared to control cells (unaffected or affected with known MDs). By identifying, for the first time, DEGs specifically modulated in UMDs, MUMDUPSC will reveal the genes and pathways specifically contributing to the diseases. It will represent a proof of concept for the classification of unlabeled muscle pathologies and, in the long term, will provide innovative leads for the diagnosis and the treatment of these debilitating diseases.

Keywords: muscular dystrophy,patients hipsc,diagnosis,transcription profile,whole genome sequencing
Saturated bioisosteres of benzene and their application in drug design (BENOVELTY)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Synthetic Chemistry and Materials
Panel description: New materials and new synthetic approaches, structure-properties relations, solid state chemistry, molecular architecture, organic chemistry
Countries involved: Ukraine
Call: ERC CONSOLIDATOR GRANTS (ERC-2020-COG, 2020)
Start date: 2021-04-01
End date: 2026-03-31
Duration (months): 60.0
Total project cost (EUR): 1997500.0
EU funding (EUR): 1997500.0
Participants: 1
Project status: SIGNED

More than 500 of all existing drugs are phenyl-containing organic molecules. During the recent years, however, pharmaceutical companies struggle to deliver novel drugs to the market, because of the lack of innovative practical approaches towards novel drug-like “chemical space.” In this project, we will address this issue by developing novel saturated bioisosteres for ortho- and meta-substituted benzenes, and incorporate them into several known drugs (intiinflamatory Aceclofenac, antiviral Tipranavir, antihypertensive Oxprenolol, etc) to provide novel patent-free analogues with improved physico-chemical and biological properties.

Keywords: benzene bioisosteres,saturation,photochemistry,bicyclo 1 1 1 pentanes,cyclobutanes
Genes, Policy, and Social Inequality (GEPSI)

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: Netherlands
Call: ERC STARTING GRANTS (ERC-2020-STG, 2020)
Start date: 2021-01-01
End date: 2025-12-31
Duration (months): 60.0
Total project cost (EUR): 1499923.0
EU funding (EUR): 1499923.0
Participants: 1
Project status: SIGNED

Many important indicators of social status (such as one’s level of education, occupation, and income) have been shown to be moderately heritable, meaning that a part of the variation in social status can be explained by genetic differences across population members. I have been able to identify for the first time specific genetic variants that are robustly associated with such an indicator, namely educational attainment (Rietveld et al., 2013, Science). By methodologically advancing the estimation of the interaction between genes and environments, this proposal will settle two long lasting debates in social science genetics. First, I will show how heritability studies –despite earlier firm rejections of this position– can be informative for policies aiming to reduce social inequalities (Objective 1). Second, I will assess the critique that social science genetics attributes effects to genes which should be attributed to the environments through which these genes operate (Objective 2). In doing so, I will extend existing methodology to quantify the incremental explanatory power of genes over environmental factors such as the social status of parents (Objective 2A), and I will develop a solution for the endogenous inclusion of environmental factors in genetic summary indices (i.e., polygenic risk scores) which currently impacts the validity of gene-by-environment studies (Objective 2B). All newly developed methods will be tested extensively using simulations, and made available for others by means of free software code. Empirically, I will interact genes and various natural experiments (policy changes) to identify interventions that can ameliorate social inequalities in terms of education, occupational status, and income. For this purpose, I will draw on a unique combination of data sources including UK Biobank (~500,000 genotyped individuals) and administrative data from Statistics Netherlands which I will link to data from the Dutch Twin Registry for this project.

Keywords: social science genetics,social inequality,gene environment interaction,heritability
Targeting treatment-induced neuroendocrine prostate cancer (TARNEPC)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Reintegration panel
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Finland
Call: Individual Fellowships (H2020-MSCA-IF-2019, 2019)
Duration (months): 24.0
Total project cost (EUR): 202680.96
EU funding (EUR): 202680.96
Participants: 1
Project status: CLOSED

Current treatment options for prostate cancer include use of androgen deprivation therapies to block tumor growth but often the tumors become castration-resistant. Even the second generation antiandrogens that do have significant effect on castration-resistant tumor growth in patients are not curative. Approximately 25% of prostate cancer patients with castration-resistant disease treated with antiandrogens develop a form of prostate cancer that is completely independent of androgen receptor signaling that fuels the tumor growth. Analyses of the pathology and genomics of these patient tumors has identified that the tumor cells adapt cancer stem cell and neuronal cell characteristics. Currently, there are no treatment options for this patient group. Thus, development of novel strategies including selection of drugs that could be used to reduce the tumor growth and metastases in this patient group are desperately needed. This project aims at characterizing a novel therapeutic target against aggressive, the treatment resistant neuroendocrine prostate cancer. The success of this project may significantly benefit prostate cancer patients and provide cost-effective therapy options to be utilized in health service.

Keywords: cancer,prostate,neuroendocrine,treatment resistance,neuroplasticity
Chemical Tools to Probe the Role of Bromodomains in the Parasite Trypanosoma cruzi (jamclay)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Chemistry
Countries involved: United Kingdom
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2014, 2014)
Start date: 2016-03-24
End date: 2018-03-23
Duration (months): 24.0
Total project cost (EUR): 183454.8
EU funding (EUR): 183454.8
Participants: 1
Project status: CLOSED

Lysine acetylation is a key protein post-translational modification (PTM) found throughout the cellular environment and across the range of species. This PTM is dynamic, with histone acetyl transferases (HATs) acetylating lysine, and histone deacetlyases (HDACs) reversing the modification. In addition, proteins modules bromodomains, have been identified that bind to acetylated lysine (KAc) and mediate protein-protein interactions. In humans, bromodomains exist as part of larger proteins, many of which are involved in transcriptional regulation. Bromodomains contain a KAc-binding pocket for which small molecule ligands have been identified. These ligands prevent the interaction of bromodomains with KAc and have been invaluable in dissecting the fundamental biology mediated by bromodomain-containing proteins (BCPs). We and others have developed potent ligands for the human bromodomain and extra C-terminal domain (BET) bromodomains. These compounds have antiproliferative effects in cancer cells lines and modulate inflammation and atherosclerosis. This work led to an explosion of interest in developing BET bromodomain inhibitors, resulting in 5 compounds in clinical trials. Despite rapid progress in understanding the role of human bromodomains, their function in other species is poorly understood. Given the fundamental role played by bromodomains in humans, we hypothesise that BCPs will play equally important roles in other organisms. To understand the role of non-human bromodomains we will develop small molecule probes to study the function of BCPs in the parasite Trypanosoma cruzi. We have selected T. cruzi for two reasons: 1. Four BCPs (TcBDF1-4) have been discovered in T. cruzi; our collaborator Prof. Serra has cloned these proteins and we have the plasmids; 2. T. cruzi is the parasite that causes Chagas Disease and hence bromodomain ligands might ultimately represent a novel method of treatment for this disease.

Keywords: epigenetics,parasites,chagas disease,inhibitors,bromodomains,medicinal chemistry
Spatiotemporal regulation of localization and replication of M. tuberculosis in human macrophages (DynaMO_TB)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator 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: United Kingdom
Call: ERC Consolidator Grant (ERC-2017-COG, 2017)
Start date: 2018-09-01
End date: 2024-08-31
Duration (months): 72.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: SIGNED

Mycobacterium tuberculosis (Mtb) is a very successful intracellular pathogen: in 2014, tuberculosis (TB) caused 1.5 million human deaths (World Health Organisation). To cause disease and disseminate to other hosts, Mtb needs to replicate within human cells. In spite of its enormous relevance for TB pathogenesis, the precise sites of Mtb replication in host cells remain unknown. This surprising gap in knowledge is in part due to the lack of appropriate imaging technologies that have precluded comprehensive understanding of the fundamental biology that underpins Mtb-host cell interactions critical to design rational interventions. Here, we propose to use a series of cutting-edge imaging approaches in human macrophages to: (1) define how the dynamic interactions between Mtb populations and organelles impact Mtb replication; (2) identify critical host and bacterial components that regulate Mtb replication and (3) characterise the host cell death pathways that control Mtb replication. For this, we will benefit from technologies developed in our group to image and quantify Mtb localisation and replication, such as live cell imaging, super resolution (SR) microscopy and correlative live cell 3D- electron microscopy (CLEM). We will refine these approaches to challenge the current limits of cell-based, high content imaging by combining human stem cell-derived macrophages with adhesive micropattern technologies for single cell analysis; this allows us to identify where and when Mtb replicate and how the interplay between host cells and Mtb impacts this process. Together, this proposal can uncover novel cellular pathways defining the intracellular sites that allow or restrict Mtb replication in human macrophages, thereby advancing the fields of both cell and infection biology. The characterization of the site of intracellular replication of Mtb can open avenues for a deeper understanding of human TB pathogenesis and facilitate development of vaccines and antibioo be here soon