Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Exploiting hybrids between annual and perennial plant species to identify genes conferring agronomically important traits (HYLIFE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-07-31
Duration (months): 66.0
Total project cost (EUR): 2490624.0
EU funding (EUR): 2490624.0
Participants: 1
Project status: CLOSED

Flowering plants exhibit a variety of different life cycles. This variation contributes in nature to adaptation to diverse environments and in agriculture to optimising crop yield. Annual monocarpic species flower once during their life, produce seeds and then undergo generalized senescence leading to death of the plant. By contrast polycarpic perennials survive seed production and live for many years flowering repeatedly. Most of our major crops are monocarpic annuals but perennials predominate in many ecological niches. Perennials exhibit phenotypic traits that would be advantageous for crops, such as an extended growing season, long duration of flowering and seed set as well as longer roots that more efficiently utilize nutrients and water supply. The high productivity of perennials explains their current use as sources of biomass. I propose here to use the progeny of hybrids between annual and perennial species in the Brassicaceae to isolate genes that confer key differences between these life histories. The utility of such genes in improving annual crops will then be tested. Arabis alpina and Arabis montbretiana are sister species that are respectively perennial and annual. We produced hybrids between these species and from them derived segregating populations by backcrossing. Here I propose to extensively genotype and phenotype these populations to identify genes promoting or suppressing senescence after flowering as well as those controlling the duration and extent of flowering. Orthologues of these genes will be identified in closely related Brassica species and alleles conferring perennial traits introduced into annual oil seed rape using genetic as well as transgenic strategies. Particularly those genes suppressing senescence and extending the duration of flowering will be tested for their effects on yield. This knowledge-based approach to introducing perennial traits into annual crops is expected to generate novel phenotypic variation that enhances yield.

Keywords: plant genetics plant reproduction
Structure function and pharmacology of calcium-activated chloride channels: Anoctamins and Bestrophins (ANOBEST)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2020-01-31
Duration (months): 72.0
Total project cost (EUR): 2176000.0
EU funding (EUR): 2176000.0
Participants: 1
Project status: CLOSED

Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.

Keywords: ion channel structure and function,x-ray crystallography of eukaryotic membrane proteins,electrophysiology,calcium activated chloride channels,ion channel pharmacology
Rome's Mediterranean Ports (ROMP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: The study of the human past
Countries involved: United Kingdom,Italy,France,Germany,France,Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 2498804.8
EU funding (EUR): 2498804.8
Participants: 6
Project status: CLOSED

Rome was connected to its Mediterranean provinces by commercial routes articulated through networks of ports acting as poly-functional nodes. Ships, people and goods moved along these, drawing the micro-regions of the Mediterranean into closer economic and commercial relationships with the City. Central to the success of these networks were the major ports through which were channelled major commercial flows moving between Rome and its maritime hub at Portus, and its Mediterranean provinces, and their relationships to lesser regional and anchorages. All of them can be described in terms of loosely configured “port-systems” that ensured the movement of ships and their cargoes around the Mediterranean. Some of these, particularly in the eastern Mediterranean, can be traced back to the Hellenistic or earlier periods. ROMP will address specific questions relating to the capacities of and inter-connections between a range of 30 ports in ways that will allow us to better understand their role in helping ensure the cohesion and integrity of the Roman Mediterranean during the imperial era. These concern (1) the layout of Roman ports, (2) the organization of commercial activity focused at them, (3) hierarchies of ports, and (4) pan-Mediterranean commercial and social connections between ports. In addressing them, the project will apply suites of existing techniques in archaeology, ancient history and palaeo-environmental studies to a range of ports. It is an approach that builds upon the PI's belief in the value of integrating archaeological techniques and historical approaches to the study of the past, and the interpretation of individual port sites within a broader Mediterranean context. In so doing, the project moves beyond the state of the art in port studies, and raises issues that are key to better understanding the unprecedented degree of economic, social and political convergence that was achieved by the Roman empire during the imperial era.

Keywords: roman,ports,harbours,mediterranean,commerce,supply,ships,hierarchies,networks,geophysics,geomorphology,maritime,epigraphy,computing,pollution,onomastics,entrepots,anchorages.
Engineering Cytokines for Super-Affinity Binding to Matrix in Regenerative Medicine (CYTRIX)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-05-01
End date: 2019-04-30
Duration (months): 60.0
Total project cost (EUR): 2368170.0
EU funding (EUR): 2368170.0
Participants: 1
Project status: TERMINATED

In physiological situations, the extracellular matrix (ECM) sequesters cytokines, localizes them, and modulates their signaling. Thus, physiological signaling from cytokines occurs primarily when the cytokines are interacting with the ECM. In therapeutic use of cytokines, however, this interaction and balance have not been respected; rather the growth factors are merely injected or applied as soluble molecules, perhaps in controlled release forms. This has led to modest efficacy and substantial concerns on safety. Here, we will develop a protein engineering design for second-generation cytokines to lead to their super-affinity binding to ECM molecules in the targeted tissues; this would allow application to a tissue site to yield a tight association with ECM molecules there, turning the tissue itself into a reservoir for cytokine sequestration and presentation. To accomplish this, we have undertaken preliminary work screening a library of cytokines for extraordinarily high affinity binding to a library of ECM molecules. We have thereby identified a small peptide domain within placental growth factor-2 (PlGF-2), namely PlGF-2123-144, that displays super-affinity for a number of ECM proteins. Also in preliminary work, we have demonstrated that recombinant fusion of this domain to low-affinity binding cytokines, namely VEGF-A, PDGF-BB and BMP-2, confers super-affinity binding to ECM molecules and accentuates their functionality in vivo in regenerative medicine models. In the proposed project, based on this preliminary data, we will push forward this protein engineering design, pursuing super-affinity variants of VEGF-A and PDGF-BB in chronic wounds, TGF-beta3 and CXCL11 in skin scar reduction, FGF-18 in osteoarthritic cartilage repair and CXCL12 in stem cell recruitment to ischemic cardiac muscle. Thus, we seek to demonstrate a fundamentally new concept and platform for second-generation growth factor protein engineering.

Keywords: cytokines,growth factors,skin repair,cartilage repair,cardiac repair,angiogenesis
The multisensory-motor unity of speech (SPEECH UNIT(E)S)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: The Human Mind and its complexity
Countries involved: France
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-09-01
End date: 2019-08-31
Duration (months): 60.0
Total project cost (EUR): 2499249.0
EU funding (EUR): 2499249.0
Participants: 1
Project status: CLOSED

This project is focussed on the speech unification process associating the auditory, visual and motor streams in the human brain, in an interdisciplinary approach combining cognitive psychology, neurosciences, phonetics (both descriptive and developmental) and computational models. The framework is provided by the “Perception-for-Action-Control Theory (PACT)” developed by the PI. PACT is a perceptuo-motor theory of speech communication, which connects in a principled way perceptual shaping and motor procedural knowledge in speech multisensory processing. The communication unit in PACT is neither a sound nor a gesture but a perceptually shaped gesture, that is a perceptuo-motor unit. It is characterised by both articulatory coherence – provided by its gestural nature – and perceptual value – necessary for being functional. PACT considers two roles for the perceptuo-motor link in speech perception: online unification of the sensory and motor streams through audio-visuo-motor binding, and offline joint emergence of the perceptual and motor repertoires in speech development. This provides the basis for the two parts of the project. In the “Extracting Units” action, we shall study how audio-visuo-motor speech units are extracted online in the human brain. This involves analysis of the joint properties of audio, video and motor stimuli gathered in a multimodal corpus; behavioural and neurophysiological data on the extraction of coherent streams within a speech scene and on the segmentation of streams into coherent audiovisual units; and elaboration of neurocomputational models of the audio-visuo-motor binding process. In the “Developing Units” action, we shall gather phonetic data on the joint development of perception, action and phonology, and implement and test various kinds of computational models, to assess how perceptuo-motor speech units emerge and evolve in the course of acquisition, reacquisition, evolution or learning of a given phonological system.

Keywords: perceptuo-motor interactions - audiovisual binding - computational cognitive models - speech development - bayesian modelling - phonetics and phonology - phonological units
Novel cancer vaccines with virus based cDNA libraries and monitoring for resistant tumour cell populations in prostate cancer (ONCOVIRVAX)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 2493155.0
EU funding (EUR): 2493155.0
Participants: 1
Project status: CLOSED

Prostate cancer is a huge burden of disease in Europe and the world and patients frequently relapse after initial attempts at the cure of localised disease. Cancer vaccination has activity but is only moderately effective. My ERC Advanced Award will use novel translational approaches to take a highly novel vaccine strategy which is excellent in mouse models towards a clinical vaccine for prostate cancer patients. We have developed a novel strategy for anti-prostate cancer vaccination based on the expression of cDNA libraries in viral vectors. Using vesicular stomatitis virus and prostate and melanoma derived libraries, this is curative in mice and we have established its mechanisms and the key antigenic determinants (Nature Medicine, Nature Biotechnology). We now have to translate this radically new vaccine strategy to the clinic. My ERC Award will be used to develop the vaccine strategy in an adenovirus vector, optimise viral constructs for optimal immunological effect and evaluate these in mouse prostate cancer and human in vitro immune systems. I hypothesised that in the clinic, the emergence of resistant populations of tumour cells from heterogeneous human cancers is likely to be a key factor in clinical failure. We will study resistant and recurrent tumours in mice using immunological and proteomic approaches to tumours and plasma in order to identify potential mechanisms of resistance to the vaccine, and potential blood protein biomarkers of resistance, which will allow us to incorporate strategies to avoid resistance in our clinical programme. In five years we aim to open phase I clinical trials. The award will fund the essential original translational science to turn the highly novel scientific strategy into a potential clinical strategy. Work to take the optimal adenoviral library vaccine into Good Manufacturing Practice and clinical trial will require commercial partnership and separate funding.

Keywords: cancer vaccine,prostate cancer,virus based cdna libraries
UV-Completion through Bose-Einstein Condensation: A Quantum Model of Black Holes (SELFCOMPLETION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Fundamental constituents of matter
Countries involved: Germany,Spain
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1167183.0
EU funding (EUR): 1167183.0
Participants: 2
Project status: CLOSED

The project addresses the two greatest unresolved problems in quantum field theory and gravity. The question of UV-completion beyond the Planck length and the mysteries of black holes. It is grounded on a recent program of research where we have put forward a fundamentally different unifying approach to both of these problems. This approach is based on modeling Black Holes as self-sustained Bose-Einstein condensates of long wave-length gravitons with the very peculiar property of being stuck at the critical point of a quantum phase transition. This quantum model of black holes is the outcome of understanding the UV-completion of gravity not taking place at the expense of some new dynamics of very short-wavelength degrees of freedom but rather at the expense of long-wavelength collective excitations of the above graviton Bose-Einstein condensate. Apart of being of undoubted theoretical value for our understanding of black hole physics and its role in the UV-completion, the new framework has important implications for astrophysics, for LHC searches of micro black holes and for studies of alternative UV-completions of the Standard Model, as well as for making connections between gravity and condensed matter physics, both theoretical and experimental. Our project is fully devoted to the exploration of this new framework with special emphasis in the development of concrete experimental predictions.

Keywords: black hole physics,quantum gravity
Formation of the First Stars (STARLIGHT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Universe sciences
Countries involved: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 2464896.0
EU funding (EUR): 2464896.0
Participants: 1
Project status: CLOSED

The appearance of the first stars marked a primary transition in cosmic history. Their light ended the so-called “dark ages”, and they played a key role in the metal enrichment and the reionization of the Universe, thereby shaping the galaxies we see today. Understanding high-redshift star formation is central to many areas of modern astrophysics. However, studying stellar birth in the early Universe is a relatively young field of science, and so still little is known about the origin and observable characteristics of the first stellar populations. Shedding light on the physical processes that govern the formation of stars in the early Universe requires a concerted, multi-facetted approach that combines a range of complementary expertise and innovative techniques. Using novel, high-resolution computer simulations we will (1) identify the physical phenomena that led to the formation of the first and second generations of stars in a systematic and quantitative way, (2) determine their mass distribution, which is the key parameter setting their lifetimes, luminosities, and chemical yields, (3) study the influence of the first stars on their surrounding environment, and (4) by doing so learn more about the subsequent cosmic evolution. We will set up a comprehensive theoretical and computational framework that enables us for the first time to make clear predictions and to compare our results with observational data from the high-redshift Universe as well as from the oldest stellar population in the Milky Way.

Keywords: formation of the first stars -- physical processes in the high-redshift universe -- galactic archeology
Understanding death-receptor signaling and physiology in the nervous system: A roadmap for the development of new treatments to neurodegenerative diseases and neurotrauma (P75NTR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Sweden
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-06-01
End date: 2020-05-31
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The aim of this proposal is to elucidate the molecular mechanisms and physiological relevance of death-receptor signaling in the nervous system and to harness this knowledge for the development of novel treatments to neurodegenerative diseases and neurotrauma. The main focus is on the p75 neurotrophin receptor (p75NTR), which is predominantly expressed in the developing nervous system and is highly induced upon different types of adult neural injury. Additional studies on other death receptors, such as DR6, are also described. p75NTR signaling can induce neuronal death, reduce axonal growth and decrease synaptic function, hence there is a good rationale for inhibiting p75NTR in neural injury and neurodegeneration. Recent discoveries from my laboratory have clarified the mechanism of p75NTR activation and provided new insights into the underlying logic of p75NTR signaling, paving the way for a genetic dissection of p75NTR function and physiology. These discoveries have open new avenues to elucidate the molecular mechanisms underlying ligand-specific responses and downstream signal propagation by death-receptors, unravel the physiological relevance of death-receptor signaling pathways in health and disease, and develop new strategies to block death-receptor activity in neural injury and neurodegeneration. To drive progress in this research area it is proposed to: i) Elucidate the mechanisms by which p75NTR and other death receptors become activated by different ligands and elicit distinct, ligand-specific cellular responses; ii) Elucidate the mechanisms underlying the specificity and diversity of p75NTR signaling and decipher their underlying logic; iii) Elucidate the physiological significance of distinct p75NTR signaling pathways through genetic dissection in knock-in mice; iv) Harness this knowledge to identify and characterize novel p75NTR inhibitors. This is research of a high-gain/high-risk nature, posed to open unique opportunities in research & development.

Keywords: neurotrophic factors,nerve growth factor,neurotrophins,p75ntr,neuronal death,neurodegeneration,regeneration,axon growth,drug discovery