Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Macroecological studies of long-term historical constraints on functional diversity and ecosystem functioning across continents (HISTFUNC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Denmark
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1499930.0
EU funding (EUR): 1499930.0
Participants: 1
Project status: CLOSED

Earth’s environment is ongoing massive changes with strong impacts on ecosystems and their services to human societies. It is thus crucial to improve understanding of ecosystem functioning and its dynamics under environmental change. I propose to do this by assessing the novel hypothesis that ecosystem functioning is subject to long-term constraints mediated by biodiversity effects and driven by past climate change and other historical factors. If supported, we will have to rethink ecosystem ecology, as traditionally ecosystem functioning is understood as the outcome of contemporary environmental drivers and their interplay with dominant species. I will employ an unconventional macroecological approach to ecosystem ecology to investigate this hypothesis for major organism groups and ecosystems across continents, modeling effects of historical factors such as past climate change. My specific objectives are to assess if and how (1) large-scale patterns in functional diversity of a key producer group, vascular plants, and (2) a key consumer group, mammals, are affected by historical factors; (3) if and how plant and mammal functional diversity are linked, and, if such links exist, how and to what extent they are shaped by historical factors; (4) if and how large-scale patterns in vegetation-related ecosystem functioning are shaped by historical factors; (5) if ecosystem functioning is linked to diversity of plants and mammals, and if such links exist, if they are shaped by historical factors; and finally (6) directly translate my findings into a novel framework for predicting spatiotemporal dynamics of ecosystem functioning that accounts for historical constraints. The project relies on extensive geospatial data now available on ecosystem functioning, species distributions, and functional traits as well as on paleodistributions, phylogenies, paleoclimate, environment, and human impacts, in combination with advanced statistical and mechanistic modeling.

Keywords: macroecology,functional diversity,ecosystem functioning,geographical ecology,historical factors
Unravelling environmental exposures in the core axis of ageing (ENVIRONAGE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Belgium
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-03-01
End date: 2018-02-28
Duration (months): 60.0
Total project cost (EUR): 1473910.0
EU funding (EUR): 1473910.0
Participants: 1
Project status: CLOSED

AGEing is a complex phenotype responsive to a plethora of ENVIRONmental inputs (ENVIRONAGE). Age related conditions in adults often find their origin in risk factors operative in early life. The molecular mechanisms behind these phenomena remain largely unknown. Mitochondria are involved in a variety of critical cell functions, including oxidative energy production and programmed cell death. Recently, I established in a study of 175 newborns, a strong association between mitochondrial DNA content and in utero exposure to particulate air pollution. Telomere length is highly heritable and erosion leads to an increasingly vulnerable structural integrity of the chromosomes. It is considered a marker of overall biological age compared with chronological age. In this regard, I demonstrated the heritability of telomere length and the influence of smoking on telomere erosion. These results support the ENVIRONAGE hypothesis, i.e. that environmental inputs influence biomolecular markers of ageing including mitochondrial function, telomere length along with DNA repair and epigenetics as the ‘core axis of ageing’. The aim is to establish prospective epidemiological evidence for molecular mechanisms or early biomarkers, which may underlie the origins or reflect the risk of age-related diseases and to understand its association with other processes and the influence of environmental factors. To this end, I will establish a birth cohort and a cohort in middle-aged and elderly. I measure environmental pollutants, in interaction with parameters that I consider to have an important role in the ageing process (mitochondrial function, telomere length, epigenetics and DNA repair capacity). ENVIRONAGE integrates environmental influences and molecular mechanisms on ageing. The common molecular epidemiological strategies in newborns, middle-aged and elderly to unravel the environmental influence on ageing are groundbreaking.

Keywords: air pollution,ageing,population studies,gene-environment interactions
Deciphering the Oncogenic Lesions and Pathways of B and T Cell Cancers (LYMPHOONCOGENOMICS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2019-01-31
Duration (months): 72.0
Total project cost (EUR): 1498940.0
EU funding (EUR): 1498940.0
Participants: 1
Project status: CLOSED

Lymphoid cancers are among the most common human malignancies and characteristically harbour genomic aberrations. Although databases will soon be flooded with genome sequences from thousands of tumours, interpretation and validation of these data is limited by the genetic variability and uncontrolled environmental exposures inherent to human studies. There is therefore a growing need in complementary approaches that would provide understanding of how and which genomic aberrations underlie tumour genesis. It has become apparent that the generation of DNA double strand breaks during the process of antigen receptor diversification, including RAG1/2 protein-generated DNA breaks during V(D)J recombination, are key intermediates in the appearance of lymphoid neoplasm. In this project, we propose to elucidate the molecular mechanisms, the genomic lesions and the oncogenic pathways underlying B and T cell cancers using a combination of mouse models and cutting-edge cytogenetic, genomic and transcriptomic technologies. We aim (i) to define the major genomic lesions and oncogenic pathways underlying the rapid onset of T-cell lymphomas in a unique mouse model that carries exacerbated RAG-induced genomic instability; (ii) to decipher the genomic lesions and pathways underlying B versus T lymphoma tropism; (iii) to investigate the functional interactions between RAG- and DNA damage response / DNA repair-complexes in suppressing genomic instability and lymphomagenesis; and (iv) to identify and validate lesions and genes underlying human B and T cell cancers using a cross-species oncogenomic comparative approach. In doing so, this study will also 1) increase our understanding of the fundamental mechanisms maintaining genome stability during lymphocyte development; 2) greatly improve interpretation and validation of whole genome sequencing analysis of human leukaemia and lymphoma; and 3) provide well-characterized animal models for developing and testing targeted therapeutics.

Keywords: lymphoid cancer,oncogenic lesions and genes,oncogenomics,genomic instability,dna damage response,dna repair,v(d)j recombination,rag1/2 proteins
Mechanistic dissection of myofibrillogenesis and sarcomerogenesis in insect muscle (FLIGHT MUSCLE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2019-01-31
Duration (months): 72.0
Total project cost (EUR): 1496000.0
EU funding (EUR): 1496000.0
Participants: 2
Project status: CLOSED

Higher animals employ a complex muscle network for their daily movements. Proper execution of movements requires individual muscles to form at the correct positions, connect to proper tendons and produce sufficient force. Muscle development is a multi-step process: myoblasts proliferate, migrate to particular locations and fuse to myotubes. Myotubes target appropriate tendons to establish a stable connection and transition to myofibers by assembling their specific contractile apparatus in a process called myofibrillogenesis. Interestingly, Drosophila adult muscles consist of two major types: tubular striated muscles, e.g. present in legs for walking, and fibrillar flight muscles that power rapid wing oscillations required during flight. The aims of my ERC proposal will address: 1) How do transcriptional networks instruct muscle diversity? 2) Which proteins have an essential role in myofibrillogenesis in different muscle types? 3) How are myofibrils and sarcomeres built in space and time in a muscle specific manner? My entry point is a genome-wide muscle-specific RNAi screen that identified the transcription factor Salm as selector gene for fibrillar flight muscle. Salm alone is sufficient to instruct all specific properties of fibrillar muscle. We will apply a combination of next-generation mRNA sequencing and chromatin immunoprecipitation to dissect the mechanism how Salm initiates myofiber type specification. We will manipulate the identified differentially expressed individual components to assess their mechanistic role in the differential assembly of myofibrils. Detailed in vivo time-lapse analysis of wild-type and mutant muscle combined with biochemical purifications of protein complexes will lead us to a better understanding of the dynamics and molecular constraints of sarcomere formation in each muscle type. Together, this will unravel developmental principles instructing muscle morphogenesis that are conserved to vertebrates and thus are of general interest.

Keywords: drosophila. muscle,sarcomere,rnai,imaging
Genetic and Phenotypic Modelling of Bacterial Evolution (GENPHENBACT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-05-01
End date: 2018-10-31
Duration (months): 66.0
Total project cost (EUR): 1485600.0
EU funding (EUR): 1485600.0
Participants: 1
Project status: CLOSED

The dramatic success of infectious agents comes from their ability to adapt to both immune and pharmaceutical selective pressures. To uncover the dynamics of bacterial adaptation, experimental evolution has been widely used, focusing mostly on organismal fitness. Many of the observation derived from these experiments have been captured by Fisher's Geometric model of Adaptation (FGMA). Despite its success, this top-down phenotypic model is relatively abstract. In fact, its most important parameter, the number of independent phenotypes an organism expose to the action of natural selection, or phenotypic complexity, remains completely disconnected from a genetic perspective. More recently, bottom-up genotype to phenotype maps from system biology have provided an alternative to unravel the constraints regulating bacterial evolution. In the present project, I want to connect these different approaches. The interpretation of system biology models in terms of FGMA will (i) uncover the genetic determinants of phenotypic complexity, giving more genetic context to FGMA, and, (ii) transpose our understanding of evolution through FGMA to complex genotype to phenotype maps. Four different levels of integration will be used: the gene, the metabolic network, the organism and the species. I will use -antibiotic resistance gene, TEM1, to connect thermodynamic models of protein evolution to FGMA, and characterize the phenotypic complexity of a single gene, -computational models of metabolic network and experimental modification of a biochemical pathway regulation to assess the meaning of phenotypic complexity in networks, -in vitro and in vivo experimental evolution coupled with genome sequencing and mutant reconstruction to assess the molecular bases of changes in beneficial mutation rates during organismal adaptation, - faeces of well characterised human twins to assess the factors of the human gut's environment that shape the genetic diversity of the Escherichia coli species.

Keywords: microbial population genetics -experimental evolution -microbiota
Molecular photoacoustic imaging during ultrasound-guided interventions (MOPHIM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: United Kingdom
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-12-01
End date: 2017-11-30
Duration (months): 60.0
Total project cost (EUR): 1499231.0
EU funding (EUR): 1499231.0
Participants: 1
Project status: CLOSED

During minimally invasive procedures, accurate identification of tissue targets is of critical importance to maximise clinical outcomes. Ultrasound imaging is widely used for real-time guidance, but in many clinical contexts it provides inadequate contrast for tissue targets. The overall objective of this translational research proposal is to develop and test a novel framework for guiding minimally invasive procedures that will dramatically enhance image contrast for a wide range of tissue structures. One of the central components of this framework will be a new modality called photoacoustics, which involves acoustic imaging of specific molecular tissue constituents that absorb pulsed excitation light. With Objective 1, we will combine ultrasound imaging with photoacoustic imaging into a novel clinical system that will be optimised for guiding minimally invasive procedures in human patients. With Objective 2, we will obtain multi-spectral photoacoustic images that provide contrast for molecules such as haemoglobins, water, and lipids, and we will co-register them with ultrasound images. With Objective 3, we will perform pre-clinical and clinical pilot studies to assess the potential of the new image guidance framework for improving the accuracy of particular minimally invasive procedures in the field of interventional pain management. This proposal is timely because there is intense scientific and clinical interest in photoacoustic imaging, but this modality has not yet been extended to the guidance of minimally invasive procedures. With a Starting Grant from the ERC, I will initiate a multi-disciplinary translational research group that is focused on developing new imaging technologies for improving the clinical outcomes of minimally invasive procedures.

Keywords: photoacoustic imaging,ultrasound imaging,medical devices,optical spectroscopy,interventional pain management,interventional oncology
Nano-Sensitizer Cancer Cell Targeted Radiotherapy (NASTAR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Denmark
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-04-01
End date: 2019-02-28
Duration (months): 71.0
Total project cost (EUR): 1498731.0
EU funding (EUR): 1498731.0
Participants: 1
Project status: CLOSED

Targeted chemotherapy in combination with external beam radiation therapy (radiotherapy) is a promising approach to significantly improve the therapeutic outcome for cancer patients. To achieve this, it is essential to develop drug delivery technology that specifically delivers the chemotherapeutic drugs to cancerous tissue. Radiotherapy is an indispensable part of modern cancer treatment; however, despite efforts in improving planning and execution of treatment, the unbalance between therapeutic benefit and side effects limits cure rates, and new approaches are needed to bring to fruition the full potential of radiotherapy. Today, there is considerable focus on systemically administered radiosensitizers for enhancing the effect of radiotherapy and clinical investigations have shown promising results; however, radiosensitizer use is hampered by considerable side effects due to lack of drug targeting to the cancerous tissue. In the first phase of this project, the aim is to develop tumor targeted nanocarrier delivery systems of radiosensitizers to enhance their therapeutic potential and provide a more efficient and site-directed effect of radiotherapy. In the second phase of the project, nanocarriers for tumor specific delivery of checkpoint inhibitors of cancer cell repair mechanisms will be investigated as an additional targeting strategy for sensitizing cancer cells to radiotherapy. The idea is to circumvent cell cycle checkpoints of DNA damage induced by tumor radiation and thereby enhance mitotic catastrophe. This approach will in combination with the delivery of conventional radiosensitizer drugs, further lower the radiation dose needed to induce irreversible damage to cancer cells. Thus, the project aims to develop targeted nanocarriers for high precision delivery of radiosensitizing drugs to cancerous tissue for enhancing the effect of radiotherapy. We aim to demonstrate the applicability and clinical potential of this new approach within the project period

Keywords: radiotherapy,liposome,drug delivery,radiosensitizer,cancer imaging,nanocarrier
Uncovering the role of new synaptic adhesion molecules in encoding synaptic connectivity in the brain (SYNAPSECODE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Belgium
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2018-01-31
Duration (months): 60.0
Total project cost (EUR): 1718070.0
EU funding (EUR): 1718070.0
Participants: 1
Project status: CLOSED

Synapses connect neurons into a network that encodes our thoughts, memories and personalities. Loss of synaptic connectivity is thought to underlie a variety of cognitive disorders such as autism, schizophrenia and Alzheimer’s disease, but little is known about the molecules and mechanisms that establish and maintain the precise patterns of synaptic connectivity in the brain. Neither is it understood how perturbed synaptic connectivity affects cognitive function. The synaptic adhesion molecules that connect pre- and postsynaptic partners across the synaptic cleft provide the key to understand these processes. I hypothesize that the proper formation and function of synaptic connections depends on synapse-specific complexes of adhesion molecules. Together, these complexes form a synaptic adhesion code that specifies synaptic connectivity and contributes to the functional and structural diversity of synapses in the brain. In my preliminary studies, I have identified a large complex of novel synaptic adhesion molecules that is required for normal synapse function, and is ideally suited to confer precise synaptic connectivity. Using in vivo manipulation of these novel synaptic adhesion molecules, I will uncover how the diversity in synaptic adhesion complexes contributes to the specification of synaptic connectivity and the diversity of synapses. Furthermore, I will determine how loss of these novel adhesion molecules affects cognitive function. This will yield new insights in the molecular and cellular mechanisms that underlie the establishment of precise synaptic connectivity in the brain. Ultimately, this insight will guide the development of new strategies for the treatment of cognitive disorders.

Keywords: synaptic adhesion,connectivity,synapse development,synapse loss,synaptic transmission
3Ps Plastic-Antibodies, Plasmonics and Photovoltaic-Cells: on-site screening of cancer biomarkers made possible (3PS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Portugal
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2018-04-30
Duration (months): 63.0
Total project cost (EUR): 998584.0
EU funding (EUR): 998584.0
Participants: 1
Project status: CLOSED

This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell. Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency. The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.

Keywords: cancer biomarkers,biomimetic materials,plastic antibodies,molecular imprinting,solar cells,biosensing device,eye detection,screening