Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The Proteolytic Machinery of the Plant Apoplast: from Basic Understanding to Improved Recombinant Protein Production (GREENPROTEASES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Medical Biotechnology
Countries involved: United Kingdom
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-07-01
End date: 2020-06-30
Duration (months): 72.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

The plant proteolytic machinery involves over 700 proteases that control the (in)activation of proteins. Surprisingly, although every protein is regulated by proteolysis, only very few natural substrates of plant proteases have been identified, and the diverse roles of e.g. secreted proteases are still poorly understood. These questions have become even more urgent since glyco-engineered plants are increasingly used for the production of recombinant proteins (RPs) to produce therapeutic antibodies, enzymes and hormones. Notably, transient expression by infiltrating leaves with Agrobacterium cultures (agroinfiltration) is cheaper, safer, more scalable and faster than any other protein expression system. However, glycosylated RPs are secreted into the apoplast where they are cleaved and degraded by plant proteases, many of which accumulate upon agroinfiltration. Therefore, secreted plant proteases cause heavy yield losses and obstruct the true potential of molecular farming in plants. The aim of this project is to comprehensively understand the roles of proteases in the plant apoplast and to use this knowledge to improve recombinant (glyco)protein production in plants by targeted protease depletion. To achieve this aim, my four objectives are to: 1) identify the major apoplastic proteases and their natural substrates and unravel proteolytic pathways; 2) annotate biological roles to secreted proteases in cellular homeostasis and microbial colonization; 3) understand substrate selection and develop software to predict cleavage sites in apoplastic substrates; 4) improve RP production by targeted (multi)protease depletion. My expertise on secreted plant proteases puts me in an excellent position to develop a model system for proteolysis in plants and solve a key problem in a new, growing industry in Europe. This project will add a new, exciting direction to my research program and connect basic and applied science.

Keywords: protease,apoplast,nicotiana benthamiana,agrobacterium tumefaciens,protease substrates,agroinfiltration,recombinant proteins
Multiscale regulation of epithelial tension (TENSIONCONTROL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Spain
Call:  (ERC-2013-CoG, 2013)
Start date: 2015-01-01
End date: 2019-12-31
Duration (months): 60.0
Total project cost (EUR): 1981761.45
EU funding (EUR): 1981761.45
Participants: 1
Project status: CLOSED

Throughout development and adult life, the growth and remodelling of living tissues is determined by a complex interplay between chemical and physical cues. Among such physical cues, mechanical tension is emerging as central regulator of cellular fate and function. To explain tension regulation, current research emphasizes molecular mechanisms at an ever increasing level of detail. How these local mechanisms are integrated to give rise to global patterns of tissue tension is unknown, however. The goal of this project is to provide a multiscale understanding of tension regulation within epithelial cell monolayers. We propose two pairs of competing mechanisms for tension regulation: fluidization vs. reinforcement and cell division vs. apoptosis. These competing mechanisms are inherently multiscale in the sense that they span and couple multiple levels of tissue organization, from the local actomyosin contraction to the multicellular rearrangement. For each of these competing mechanisms we plan to study how local processes and interactions give rise to global tensional patterns. To do this, we propose to develop an integrated experimental setup to map and perturb monolayer tension at different length scales. We expect this project to unveil the repertoire of mechanisms that epithelial tissues use to regulate their tension and dynamics.

Keywords: cell migration,cytoskeleton,tissue dynamics,epithelium,cell mechanics,tissue mechanics,bioengineering
Highly accurate Isogeometric Method (HIGEOM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Mathematics
Countries involved: Italy
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-06-01
End date: 2020-05-31
Duration (months): 72.0
Total project cost (EUR): 928188.0
EU funding (EUR): 928188.0
Participants: 1
Project status: CLOSED

Partial Differential Equations (PDEs) are widely used in science and engineering simulations, often in tight connection with Computer Aided Design (CAD). The Finite Element Method (FEM) is one of the most popular technique for the discretization of PDEs. The IsoGeometric Method (IGM), proposed in 2005 by T.J.R. Hughes et al., aims at improving the interoperability between CAD and FEMs. This is achieved by adopting the CAD mathematical primitives, i.e. Splines and Non-Uniform Rational B-Splines (NURBS), both for geometry and unknown fields representation. The IGM has gained an incredible momentum especially in the engineering community. The use of high-degree, highly smooth NURBS is extremely successful and the IGM outperforms the FEM in most academic benchmarks. However, we are far from having a satisfactory mathematical understanding of the IGM and, even more importantly, from exploiting its full potential. Until now, the IGM theory and practice have been deeply influenced by finite element analysis. For example, the IGM is implemented resorting to a FEM code design, which is very inefficient for high-degree and high-smoothness NURBS. This has made possible a fast spreading of the IGM, but also limited it to quadratic or cubic NURBS in complex simulations. The use of higher degree IGM for real-world applications asks for new tools allowing for the efficient construction and solution of the linear system, time integration, flexible local mesh refinement, and so on. These questions need to be approached beyond the FEM framework. This is possible only on solid mathematical grounds, on a new theory of splines and NURBS able to comply with the needs of the IGM. This project will provide the crucial knowledge and will re-design the IGM to make it a superior, highly accurate and stable methodology, having a significant impact in the field of numerical simulation of PDEs, particularly when accuracy is essential both in geometry and fields representation.

Keywords: discretization of pdes,isogeometric analysis,spline theory,non-uniform rational b-splines,finite element method.
New isotope tracers for core formation in terrestrial planets (ISOCORE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Earth System Science
Countries involved: Germany
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-02-01
End date: 2019-10-31
Duration (months): 69.0
Total project cost (EUR): 1940040.0
EU funding (EUR): 1940040.0
Participants: 1
Project status: CLOSED

This proposal aims to develop new isotopic tools designed to constrain the core formation process in the Earth. We will use isotopic fractionations imparted by metal-silicate equilibration during core formation to obtain new and firm constraints on (i) the physical and chemical processes during formation of the Earth's core; and (ii) on the origin of volatile elements and the volatile accretion history of the Earth. The underlying concept of our approach is to compare observed mantle-core isotopic fractionations (determined on natural samples) to the experimentally-determined isotope fractionation between liquid metal (core analogue) and liquid silicate (mantle analogue). Since the magnitude of isotope fractionation is strongly temperature-dependent, this comparison will enable us to evaluate core formation temperatures. I propose to use the stable isotope systematics of W, Mo and Cr to assess as to whether core formation temperatures for the Earth, Moon, Mars and asteroids are different, as would be expected if metal segregation in the Earth involved metal-silicate equilibration in a deep magma ocean. If instead all bodies have similar core formation temperatures, then formation of the Earth's core most probably involved some disequilibrium induced by direct core mergers during accretion from differentiated bodies. The second major theme of the proposed research uses Ge and Sb stable isotopes to trace the origins of Earth's volatiles. The combined investigation of Ge and Sb isotope fractionations in natural samples and metal-silicate equilibration experiments will enable us to determine as to whether Ge and Sb, and with them other volatile elements, show an isotope signature resulting from core formation. Identifying such a signature would provide the unequivocal evidence that volatile elements were delivered to the Earth during core formation and not subsequently, after the core had formed.

Keywords: core formation,stable isotope fractionation,origin of volatiles,planetary accretion,isotope geochemistry,terrestrial planets,siderophile elements
Control of translation efficiency in proliferating and differentiated mammalian cells (TRNAPROLIF)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Israel
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-12-31
Duration (months): 69.0
Total project cost (EUR): 1540000.0
EU funding (EUR): 1540000.0
Participants: 1
Project status: CLOSED

Translation maps the transcriptome onto the proteome. It is regulated at the initiation levels and also by mRNA secondary structure, and – our current focus – by the interplay between the mRNA and tRNA pools. Although a lot is known about the mechanics of translation, its effects on physiology, particularly on proliferation and differentiation in mammals presents major open questions. tRNAProlif offers an approach that consists of genome-wide measurements and analyses of the tRNA and mRNAs pools, and the interplay between them, in proliferative and differentiated cells. The project will explain how changes in translation affect, and are affected by, these two states. We rely on our preliminary results that show a striking dichotomy in codon usage: genes involved in cellular proliferation have distinct codon usage compared to genes involved in differentiation and other multi-cellular process. Further, the tRNA pool consists of two distinct sub-populations: tRNAs whose codons are enriched among the proliferation genes are induced in proliferation and cancer, and tRNAs whose codons are enriched in differentiation genes are repressed in proliferation and are induced in differentiation. Towards understanding this “tRNA Switch” we aim at: Causality: We will determine whether the tRNA pool affects the proliferation/differentiation status of cell. Conversely, we will determine the effects of the proliferation/differentiation status on the tRNA pool. Regulation: We will establish the regulatory scheme that governs the “tRNA Switch”: we will determine the effects of transcriptional and post-transcriptional regulation on the tRNAs, depending on cell state. We will determine how the balance between the two tRNA sub-populations affects the proteome. Evolution: We will conduct comparative genomics of regulation of tRNA availability and codon usage and its effect on physiology in multiple species.

Keywords: translation,cancer,genomics
The histone H3.3 variant in brain cancer pathogenesis (H3.3CANCER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: United Kingdom
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-05-01
End date: 2019-04-30
Duration (months): 60.0
Total project cost (EUR): 1999998.0
EU funding (EUR): 1999998.0
Participants: 2
Project status: CLOSED

Epigenetic reprogramming is a hallmark of brain cancer. Remarkably, driver mutations of the histone H3.3 variant and its loading machinery have been recently found in paediatric glioblastoma multiforme (GBM), a devastating neoplasm originating from transformed neural precursors. Thus, the very basic building blocks of chromatin can be mutated in cancer. The present challenge is to define at which level altered H3.3 loading influences GBM pathogenesis and provide clues into the underlying mechanisms. Based on work from our group and others, we hypothesise that alterations of H3.3 function/deposition would lead to epigenetic changes, deregulated transcription at bivalent loci and other genomic regions, and alterations of telomere maintenance mechanisms, in turn contributing to tumourigenesis. The main objectives of this proposal are to: 1. Examine the impact of H3.3 mutations on brain cancer pathogenesis, by determining the effect of mutant H3.3 expression on neural precursor cell transformation (A), and tumour maintenance (B). 2. Define the molecular changes caused by incorporation of H3.3 mutants into the genome and their involvement in tumourigenesis, by A. determining the genome-wide distribution of WT and mutant H3.3 proteins, B. identifying mutant H3.3-driven transcriptional and epigenetic changes, C. defining effects on telomere maintenance mechanisms, and D. connecting mutant H3.3-driven molecular changes to the biological phenotypes. The discovery of mutations in histones and their loading machinery represents a paradigm change in the field of cancer epigenetics. We anticipate this study to provide key insights into the role of these alterations in chromatin regulation and cancer pathogenesis. More broadly, this work will increase our understanding of the fundamental mechanisms governing chromatin modification in mammalian cells.

Keywords: aetiology,brain cancer,stem cells
XUV/X-ray Multidimensional Spectroscopy of Fundamental Electron Dynamics and Impulsive Control of X-ray Light (X-MUSIC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Fundamental Constituents of Matter
Countries involved: Germany
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 1983863.0
EU funding (EUR): 1983863.0
Participants: 1
Project status: CLOSED

Interaction of extreme&controlled light fields with matter is driving an ongoing revolution in our understanding of quantum physics. Controlled—pulsed—visible lasers have enabled time-dependent two-dimensional (2D) spectroscopy currently transforming chemistry, and led to key milestones such as frequency combs. Despite progress on coherent soft- and hard-x-ray pulsed sources during the last 10 years—e.g. x-ray free-electron lasers (FELs) or high-harmonic generation of laser light, nonlinear (e.g. 2D) spectroscopy or phase control of x-ray light remained a major challenge. Here, I propose to experimentally realize - (a) x-ray two- and multi-dimensional spectroscopy - (b) resonant gain without inversion and spectral control of x rays for the scientific goals - (a) time- and quantum-state-resolved measurement of fundamental few- and many-electron dynamics - (b) generation of soft-(electronic) and hard-x-ray (nuclear) frequency combs For (a), a 4-quadrant x-ray time-delay unit will generate coherently-timed pulses out of one spatially coherent beam. For (b) a new physical mechanism relating Fano to Lorentz resonances and absorption to gain by a single temporal phase will be harvested. Scientific impact: (a): Site-specific 2D-x-ray spectroscopy will phase-sensitively test&promote theory and allow to understand fundamental processes: excitation, ionization, and few-electron dynamics in atoms and molecular bonding orbitals. (b): Impulsive phase control of resonant gain and absorption represents a disruptive key technology rivalling the LASER especially in the hard-x-ray domain, where long-lived population inversion in dense media seems impossible. Frequency combs around a well-defined (5 neV) hard-x-ray Mössbauer Fe57 nuclear transition (14.4 keV) will be demonstrated. Such combs (at >10 keV), will in the future allow the most sensitive tests of fundamental physics, e.g. quantum-electrodynamics (QED) in highly-charged ions and the variation of physical 'constants'.

Keywords: atomic,molecular and optical physics few- and many-body quantum dynamics of electrons multidimensional spectroscopy x-ray frequency combs
Coactivator-controlled transcriptional networks regulating skeletal muscle cell plasticity (MUSCLE-NET)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Switzerland
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-12-31
Duration (months): 69.0
Total project cost (EUR): 1999396.8
EU funding (EUR): 1999396.8
Participants: 1
Project status: CLOSED

Regular physical activity is linked to improved health and increased life expectancy. Inversely, a sedentary life-style is a strong and independent risk factor for many chronic diseases, including obesity, type 2 diabetes or cardiovascular disorders, as well as certain types of cancer or neurodegeneration. Interestingly however, the molecular mechanisms that mediate the health beneficial effects of exercise, or those that trigger the pathological changes in diseases, are largely unknown. The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is one of the major regulatory hubs of muscle adaptation to endurance training. Accordingly, elevated expression of PGC-1α in muscle is sufficient to induce a trained phenotype in mice. Inversely, mice lacking a functional PGC-1α gene in skeletal muscle exhibit many signs of pathological inactivity. Finally, PGC-1α expression is dysregulated in pathological contexts in human muscle, including type 2 diabetes and aging. Therefore, the study of the regulation and function of PGC-1α in muscle has the potential to yield important insights into the molecular mechanisms that control muscle health. Unfortunately, the characterization of PGC-1α is drastically hampered by the high complexity of the transcriptional network controlled by this coactivator protein, which binds to many different transcription factor binding partners in a cell context-specific manner. Moreover, PGC-1α seems to directly couple transcription to RNA processing, thereby further complicating the analysis of PGC-1α-controlled biological programs. Our proposal combines novel innovative experimental and biocomputational approaches with the physiological study of healthy and diseased muscle cells ex vivo and in different animal models targeted on PGC-1α. Together, our findings will reveal novel insights on muscle function and may substantially shape the development of exercise mimetic-based therapies.

Keywords: pgc-1alpha,skeletal muscle,exercise,transcriptional regulation,mitochondria,coactivator,rna processing,splicing,transcriptional networks,insulin resistance,type 2 diabetes,aging
Terahertz microsystems - Enabling the large-scale exploitation of the terahertz gap (TERAMICROSYS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Systems and Communication Engineering
Countries involved: Sweden
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 1727189.0
EU funding (EUR): 1727189.0
Participants: 1
Project status: CLOSED

This project envisions the wide-spread use of THz technology in various applications in our society, which is enabled by the proposed THz microsystems, providing an unprecedented way of creating highly-integrated, volume-manufacturable, cost and energy-efficient, reconfigurable and thus adaptive submillimeter-wave and THz systems. Advanced three-dimensional micromachining is used as the key enabling fabrication technology. In connection with the technology convergence of advancing microwave semiconductor technology according to international technology programmes and roadmaps, the findings of this project are expected to comprise a significant contribution towards the large-scale exploitation of the heavily sought-after frequency space between 100 GHz and 1 THz, the so-called ‘terahertz gap’. Primary application fields with high impact of the proposed technology are wireless short-range communication links to interconnect future small-cell clouds replacing the current macro-basestation radio access network, and submillimeter-wave/THz sensing with application fields including medical diagnosis, food quality control, agriculture and industrial sensors. The proposed THz microsystems are based on rectangular waveguide-technology integrated into a multi-wafer stacked silicon substrate, which integrates all passive components needed for completing a submillimeter-wave/THz system around the monolithic-microwave integrated circuits (MMIC). Novel key building blocks investigated in this proposal include platform-integrated sensor and antenna interfaces, micro-electromechanically tuneable filters, phase-shifters, impedance-matching networks and non-galvanic microsystem-to-IC interfaces. The micro-mechanical reconfigurability enables unprecedented adaptive THz systems. Key outcomes of this project are proof-of-concept prototypes of all key building blocks up to 650 GHz, and of complete THz microsystems implemented for the two key applications telecom links and medical sensors.

Keywords: terahertz,thz,microsystems,microwave engineering,millimeter-wave,submillimeter-wave,communication links,medical sensors,microelectromechanical systems,mems