Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Less is more: Single Cell Analysis of Zebrafish Blood Development (ZF_Blood)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Cellular, Developmental and Regenerative Biology
Panel description: Structure and function of the cell, cell-cell communication, embryogenesis, tissue differentiation, organogenesis, growth, development, evolution of development, organoids, stem cells, regeneration, therapeutic approaches
Countries involved: United Kingdom
Call: ERC Starting Grant (ERC-2015-STG, 2015)
Start date: 2016-05-01
End date: 2022-04-30
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Blood stem cells need to both perpetuate themselves (self-renew) and differentiate into all mature blood cells to maintain blood formation throughout life. However, it is unclear how the underlying gene regulatory network maintains this population of self-renewing and differentiating stem cells, and how it accommodates the transition from a stem cell to a mature blood cell. Our current knowledge of transcriptomes of various blood cell types has mainly been advanced by population-level analysis. However, the population of seemingly homogenous blood cells may include many distinct cell types with substantially different transcriptomes and abilities to make diverse fate decisions. To overcome these limitations, I will use single-cell transcriptome sequencing of zebrafish blood cells. I will apply an integrative strategy, combining genetic perturbation with computational sequence and network analysis methods, to reconstruct the regulatory networks that maintain the dynamic balance between different blood cell types. This will be achieved by pursuing two main aims: 1) I will create a comprehensive atlas of single cell gene expression in adult zebrafish blood cells and computationally reconstruct the blood lineage tree. I will order cells according to their most likely developmental chronology and identify genes and gene regulatory networks that define distinct cell types. The completion of the first aim will be followed by a more ambitious long-term one that is based on: 2) The in-depth functional characterisation of a subset of novel key regulators of blood formation and identified cell types in vivo. To achieve this I will generate a number of loss-of-function and transgenic zebrafish lines. By sequencing thousands of single cells, this study is poised to go beyond traditional approaches in examining the complex relationships between the continuous spectra of blood cells, and will provide unprecedented insight into the regulation of blood cell formation.

Keywords: haematopoiesis,single cell rna seq,zebrafish
Bacterial Ghost Cancer Immunotherapy - A new standard in tumour therapy based on the bacterial ghost platform technology (BGCI)

Framework: Horizon 2020 — Societal Challenges
Programme: Health, demographic change and wellbeing
Theme: Treating and managing disease
Action type: SME instrument
Countries involved: Austria
Call: Supporting innovative SMEs in the healthcare biotechnology sector (H2020-SMEINST-1-2016-2017, 2016)
Start date: 2017-03-01
End date: 2017-07-31
Duration (months): 5.0
Total project cost (EUR): 71429.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

MMalignant diseases represent a major health problem in all parts of the world and their incidence, according to the WHO/ IARC World Cancer Report 2014, will increase by 57% worldwide in the next 20 years. Standard treatment strategies for cancer including surgery, chemotherapy and targeted molecular therapy still do not guarantee complete elimination of the disease. In addition, cancer cells exhibited high capability to escape from immunosurveillance after applied treatment which was confirmed with frequently occurred relapse of disease. BIRD-C have developed Bacterial Ghost Cancer Immunotherapy (BGCI) - a novel personalised medicine approach towards vaccination against tumours. BIRD-C’s therapeutic cancer vaccines are based on personalised dendritic cells-based cancer immunotherapy that targets the tumour microenvironment using Bacterial Ghosts (BGs), the proprietary platform technology of BIRD-C. The tumour therapy strategy is to (re)stimulate the patient immune system to revert the tumour evasion and build strong humoral and cellular immune responses against patient-specific tumour antigens. Obtained results show that BGCI can generate effective response to tumours and indicate novel prospective methods for cellular cancer immunotherapy. This approach has been tested in a form of advanced personalised cancer therapy and has improved the survival of patients with solid tumours. During the project, BIRD-C will develop the manufacturing procedure and commercial scale-up strategy and also conduct a multi-centre trial with patients affected by various forms of cancer at different stages of progression to determine the tolerability and effectiveness of the treatment.

Keywords: cancer,immunotherapy,immune system,bacterial ghosts,vaccine,biotechnology
Glucose metabolism and mTOR pathway role in CD8+ T cell control of HIV-1 (GLUTORHIV)

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: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2015, 2015)
Start date: 2016-04-01
End date: 2018-03-31
Duration (months): 24.0
Total project cost (EUR): 185076.0
EU funding (EUR): 185076.0
Participants: 1
Project status: CLOSED

Antiretroviral therapy can decrease HIV-1 below the limit of detection but fails to eliminate the virus completely. One of the main goals of a HIV-1 vaccine is the generation of cytotoxic CD8 T cell responses that counteract the virus. CD8 T cells participate in the control of viremia early but progressively show weakened functions, which leads to loss of virus control. HIV controllers are a rare group of infected patients who can control the virus for years without antiretroviral therapy. CD8 T cells from HIV-controllers display an outstanding capacity to eliminate infected CD4 T cells ex vivo but the underlying mechanisms are still not understood. Preliminary data aiming at establishing a single cell transcriptional signature associated with control of HIV suggest an important role of the mTOR pathway during the chronic stage. This pathway plays a major role in glucose metabolism and CD8 T cells cytotoxic function. This raises the hypothesis that the extraordinary HIV-suppressive capacity of HIV-controllers CD8 T cells is associated with the modulation of mTOR pathway and glucose metabolism. This project aims to 1) Study the single cell gene expression of HIV-specific CD8 T cells in HIV patients longitudinally from acute to chronic stages and understand the factors linked to control and loss of function of CD8 T cells during disease progression. 2) To characterize the role of mTOR pathway in the ability of CD8 T cells from HIV-controller to eliminate infected cells and test if this pathway can be modulated to fine-tune anti-HIV CD8 T cells responses. 3) To understand if an optimal glucose metabolism is necessary for CD8 T-cells suppression of HIV and if this capacity can be improved by increasing available glucose. This work will help to understand the characteristics of effective CD8+ T cell responses against HIV and may guide the development of anti-HIV vaccines or immunotherapies to induce HIV controller-like responses in HIV-infected progressors.

Keywords: hiv cd8 t cells responses,hiv controllers,mtor,glucose metabolism,single cell gene expression
Unravelling the molecular Basis of epigenetic silencing: what factors define a gene as a Polycomb target? (AMBITION)

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: Life Sciences
Countries involved: United Kingdom
Call: Individual Fellowships (H2020-MSCA-IF-2016, 2016)
Start date: 2017-04-01
End date: 2019-03-31
Duration (months): 24.0
Total project cost (EUR): 183454.8
EU funding (EUR): 183454.8
Participants: 1
Project status: CLOSED

The current lack of mechanistic understanding regarding how Polycomb targets are selected severely limits the potential for epigenetic manipulation in many eukaryotic systems. This proposal therefore addresses a key central question in chromatin biology: which factors specify a gene for Polycomb mediated silencing? It will make use of the recent identification of a single nucleotide polymorphism within the target gene that blocks cold induced silencing of the Polycomb switching system at FLOWERING LOCUS C (FLC) in Arabidopsis thaliana. At FLC, specific DNA binding proteins (VAL1, VAL2) and their partners interact in a not yet fully understood regulatory network with Polycomb proteins, which consequently convert environmental cues (prolonged cold) into stable epigenetic memory (silencing of the gene) to achieve flowering. I hypothesise that this regulation involves components of the Apoptosis and Splicing Associated Protein (ASAP) complex, the functions of which have been linked to RNA processing and RNA quality control. Thus, these protein interactions directly link DNA sequence specificity with co-transcriptional regulation through to Polycomb mediated epigenetic gene silencing. I aim to demonstrate that multiple cis and trans factors determine Polycomb target selection and that their combined actions synergize to nucleate Polycomb complexes at FLC, and thus switch the gene from an epigenetically active to a silent state. The proposed work will be achieved through interconnected molecular, biochemical and genetic avenues. It will yield novel and comprehensive mechanistic insights into the complexity and plasticity of epigenetic regulation of Polycomb target genes in plants, with broad impact on chromatin research in other organisms.

Keywords: arabidopsis,flowering time,epigenetics,chromatin,transcription
Chemoenzymatic glyco-engineering of therapeutic monoclonal antibodies (GlycoMabs)

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: Chemistry
Countries involved: Spain
Call: Individual Fellowships (H2020-MSCA-IF-2018, 2018)
Start date: 2019-04-16
End date: 2021-04-15
Duration (months): 24.0
Total project cost (EUR): 160932.48
EU funding (EUR): 160932.48
Participants: 1
Project status: CLOSED

Monoclonal Antibodies (mAbs) have gained an important place in the therapeutic arsenal of anticancer drugs. mAbs are glycoproteins containing a conserved N-linked glycosylation site at residue Asn297 of the fragment crystallisable (Fc). Most of the mAbs approved by the EMA are commercialized as a complex mixture of glycoforms at this site. It is well stablished that the precise chemical structure of the N-linked glycan modulates the effector functions mediated by the Fc domain. Specifically, for cancer treatment applications, the lack of fucose on the glycan structure contributes to enhance the effector functions of the antibodies, via increased affinity of IgG1 for FcgRIIIa on immune cells. New strategies to glycoengineering mAbs with homogenous glycoforms and lacking fucose core on their glycan structures have become a priority for the biopharmaceutical industry in order to obtain “biosuperior” anticancer drugs. Here, we will engineer a novel fucosidase enzyme that can act on fully glycosylated mAbs in order to simplify the chemoenzymatic synthesis of antibody drugs, based on the host laboratory expertise in Carbohydrate Active Enzymes. We will address three specific aims: (1) to define the structural basis of EndoS antibody specificity; (2) to elucidate the molecular mechanisms of IgG defucosylation by AlfC; and (3) to engineer an enzyme with fucosidase activity and specific for IgG. The GlycoMabs project will provide me an excellent and unique career opportunity by learning new skills in structural biology, protein engineering and project management which will grant me a leading independent position. Moreover, I will explore the industry interest in the application of our novel enzymes to generate homogeneous and afucosylated antibodies through an intersectoral secondment. Altogether, we will contribute to construct the next generation of therapeutic glycoengineered mAbs to tailor the immune reactions and increase their clinical potency.

Keywords: carbohydrates,glycans,glycobiology,glycosyltranferases,glycoside hydrolyses,glycosylation,glycoprotein
Engaging the citizen. The impact of crowd knowledge on science. (CROWDKNOW)

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: Economic Sciences
Countries involved: Belgium
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Duration (months): 24.0
Total project cost (EUR): 178320.0
EU funding (EUR): 178320.0
Participants: 1
Project status: CLOSED

For decades, scientific activity has been firmly anchored in universities, research centres, or specialized firms’ R&D departments leading to science being considered an Ivory Tower endeavour. Making science more accessible and acceptable to the larger public is one focus of the European Commission. One possible way to achieve this goal is through crowd science, an approach that allows a wide base of (non-scientific) volunteers to participate in research projects. The potential benefit of crowd science is vast, for example, the contribution of ideas and solution by the public can widen the range of research questions that can be addressed and it can increase the acceptance of scientific findings and literacy of science in the society. While the benefit of crowd science is substantial, the vital step to reap this benefit is that scientists pick up on citizens’ suggestions and actually pursue these ideas by transforming them into research projects. Many citizens’ inputs go unaddressed because their relevance is undervalued or not recognized by scientists who are trained to interact with peers rather than layman. This can lead to a loss of valuable knowledge and might discourage citizens to contribute to crowd projects in the future. The first step to mitigate this problem is to understand what type of knowledge scientists pick up, what type of scientist participates in such endeavours and how policy can encourage further scientists in doing so. This project employs an adaptive choice-based conjoint (ACBC) analysis to (i) measure the preferences and costs of scientists to engage in crowd input and quantifies the pick-up rate of citizens’ inputs by scientists, (ii) delineates the scientists’ characteristics that engage with citizens, and (iii) defines relevant incentives for scientists to increase their engagement in crowd science projects to derive policy measures that render future crowd science actions more successful.

Keywords: organization of science,knowledge transfer,crowd science,open innovation
New algorithms for inference and optimization from large-scale biological data (INFERNET)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Research and innovation staff exchange
Action type: Marie Skłodowska-Curie actions
Panel: Physics
Countries involved: Argentina,Italy,Cuba,Switzerland,France,United Kingdom
Call: Research and Innovation Staff Exchange (H2020-MSCA-RISE-2016, 2016)
Start date: 2017-03-01
End date: 2022-12-31
Duration (months): 70.0
Total project cost (EUR): 900000.0
EU funding (EUR): 900000.0
Participants: 7
Project status: CLOSED

The tremendous technological advance underlying the ongoing genomic revolution in the life sciences has profoundly transformed biological research over the last 10-15 years. The grand challenge ahead is to leverage experimental progress like high-throughput sequencing by developing effective tools for large scale data-based inference and optimization. The goals of INFERNET rely on the transfer of ideas and methods developed in recent years at the boundary between statistical physics and information theory into the world of quantitative biology. We aim at setting up a consortium characterized by a proven track-record of high-quality research in order to implement a highly integrated program leading from the design of new algorithms to concrete biological applications. The consortium will provide the optimal environment to nurture a generation of researchers that will drive new developments at the forefront of these challenging fields. The perimeter of each individual research activity will be delimited by: (a) the research themes characterized by the toolbox and methods developed and shared within INFERNET, (b) the choice of the application domains. Principal research themes covered by the consortium will be: (i) the inference of interaction networks from data, (ii) the analysis of static and dynamical processes on networks. Application domains can be broken down into four main areas: (i) the inference and modeling of multi-scale biological networks, (ii) the rational design of biological molecules, (iii) the quantitative study of cell energetics in proliferative regimes, (iv) the characterization of functional states of large-scale regulatory networks. Each individual research project will be a puzzle piece of the wider research project, as well as tailored to suit each researcher's scientific and professional development.

Keywords: mathematical modeling,statistical inference,multi scale molecular networks,co evolution,metabolic networks,regulatory networks,molecular design,protein protein interactions
Unfoldings and Bifurcations of Polynomial Differential Systems (UBPDS)

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: Mathematics
Countries involved: Slovenia
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2014, 2014)
Start date: 2016-06-30
End date: 2017-06-29
Duration (months): 12.0
Total project cost (EUR): 78643.8
EU funding (EUR): 78643.8
Participants: 1
Project status: CLOSED

We investigate the versal unfolding and bifurcations of planar polynomial differential systems having some topological structure. Specially, we classify the systems of high degree which have centers or degenerate equilibria. Then we study the degeneracy of the system and prove the existence of versal unfoldings. All possible bifurcations of unfolding systems will be discussed and topological phase portraits of the systems are presented. Finally, we give a rigourous mathematical explanation for our results in some bio-mathematical models.

Keywords: unfolding,bifurcation,center,limit cycle,integrability
Determining centromere assembly mechanisms and improving mitotic fidelity during somatic cell reprogramming (CAiPSC)

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: Life Sciences
Countries involved: Portugal
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2015, 2015)
Start date: 2016-09-01
End date: 2019-01-28
Duration (months): 24.0
Total project cost (EUR): 148635.6
EU funding (EUR): 148635.6
Participants: 1
Project status: CLOSED

Maintaining a stable karyotype is essential for the use of pluripotent stem cells (PSCs) in regenerative medicine and translational and basic research. Although around 10-30% of PSC lines present karyotypic abnormalities, the molecular mechanisms underlying this genomic instability are largely unknown. Centromeres, the chromosomal loci that drive chromosome segregation are central to mitotic fidelity. Maintenance of centromeres in somatic cells is tightly cell cycle coupled, as centromeric chromatin assembly is strictly dependent on G1 phase transition. PSCs have an atypical cell cycle structure with truncated gap phases and proliferate at unusually rapid rates. How this affects mitotic fidelity in general, centromere assembly in particular and consequently, genomic stability is an essential question in reprogramming biology. The aim of this multifaceted project is to determine the mechanisms regulating proper chromosome segregation during somatic cell reprogramming to induced PSCs (iPSCs). By combining fluorescent labelling techniques, high-end microscopy and genome-wide analysis, this project will determine the mechanisms of centromere assembly and inheritance in PSCs, the consequences of genome-wide remodelling of chromatin marks during reprogramming on the stable epigenetic propagation of centromeric chromatin and how functional modulation of key centromere assembly factors affect mitotic fidelity. This project capitalises on the unique combination of the researcher’s experience in stem cell biology and iPSC technology and the extensive expertise in the biology of human mitosis and centromere function of the host lab. The results of this study will provide direct insight into how chromosomal segregation is controlled in PSCs and most importantly during reprogramming, which will advance our understanding of the mechanisms underlying the genomic instability of these cells and contribute to the development of strategies to obtain better and more robust iPSCs.

Keywords: reprogramming,genomic instability,centromere biology