Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Regulation of gene expression and cell fate by DNA (hydroxy)methylation (HEAVYMETHYL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Netherlands,Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-10-01
End date: 2018-09-30
Duration (months): 60.0
Total project cost (EUR): 1499776.0
EU funding (EUR): 1499776.0
Participants: 2
Project status: CLOSED

(Hydroxy)methylation of cytosine residues in eukaryotic DNA represents a major means to regulate gene expression during development. These modifications are considered to be epigenetic marks, since they have a profound impact on phenotype, but are inherited from mother to daughter cells independent of the underlying DNA sequence. Large efforts are currently underway to profile genome-wide DNA (hydroxy)methylation patterns in model organisms and in clinical studies, since aberrant DNA (hydroxy)methylation is a hallmark of cancer. Strikingly, the molecular mechanisms underlying the link between DNA (hydroxy)methylation and gene expression remain elusive. Although causal links are thought to arise from differential recruitment of transcription factors to (hydroxy)methylated DNA in a regulated manner during development, technical limitations have thus far prevented unbiased interaction screenings to investigate this hypothesis in detail. By using a unique combination of state-of-the-art quantitative mass spectrometry-based proteomics technology, genomics approaches and biochemical experiments, I will systematically investigate which proteins interact with or are repelled by (hydroxy)methylated DNA during stem cell differentiation into a neuronal lineage. Furthermore, I will investigate whether and to what extent these interactions regulate gene expression programs and lineage commitment. The results of these studies will reveal the mechanisms through which dynamic DNA (hydroxy)methylation patterns dictate cellular responses. This is anticipated to significantly increase our understanding of eukaryotic development and the role of epigenetics herein. Furthermore, these studies will pave the way for designing strategies aimed at interfering with altered epigenetics patterns in disease.

Keywords: quantitative mass spectrometry-based proteomics,next-generation sequencing,dna (hydroxy)methylation,embryonic stem cells,dna-protein interactions,neuronal differentiation
Regulation of Gene Expression by non-canonical poly(A) and poly(U) polymerases (PAPS&PUPS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Poland
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2019-01-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

In eukaryotes, almost all RNA molecules are processed at their 3’ ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases (PAPs). Recently, several new non-canonical poly(A) (ncPAPs) and poly(U) polymerases (PUPs) have been discovered that have more specific regulatory roles. In contrast to canonical ones, their functions are more diverse; some induce RNA decay while others, especially cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. Knowledge about ncPAPs and PUPs is very scarce and there are crucial questions about their functions that need to be addressed. The project has 3 parts: 1) Functional analysis of FAM46 proteins, which, according to our preliminary data, constitute a new family of active poly(A) polymerases. FAM46C is frequently mutated in myelomas and mutations in its mouse orthologue cause anaemia, thus demonstrating important biological functions of this unexplored family of proteins. 2) Elucidation of the functions of all known vertebrate ncPAPs and PUPs (7 previously known and 4 members of FAM46 family) using the chicken DT40 cell line as a model system. DT40 has an exceptionally high rate of homologous recombination, allowing easy gene targeting and generation of multiple knockouts that facilitate the study of proteins with overlapping functions. 3) Cytoplasmic polyadenylation of dormant mRNA molecules activates translation in neurons, gametes and reticulocytes. In neurons, it occurs in axons and dendrites following synaptic stimulation while in oocytes, it is induced by progesterone. The exact impact on gene expression is not well defined due to a lack of technologies identifying cytoplasmically polyadenylated transcripts. We will develop a novel detection method for ongoing RNA polyadenylation to assess the biological significance of cytoplasmic polyadenylation. This part of the project will be developed using mouse synaptoneurosomes and then transferred to reticulocytes and possibly oocytes.

Keywords: poly(a) polymerase,poly(u) polymerase,tutase,polyadenylation,rna decay,local translation,dt40,multiple myeloma,synaptoneurosomes,reticulocytes,synaptic plasticity
High rate and compact quantum random number generator (MAMBO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Proof of concept grants
Action type: Support for frontier research (ERC)
Countries involved: Spain
Call:  (ERC-2011-PoC, 2011)
Start date: 2012-05-01
End date: 2013-04-30
Duration (months): 12.0
Total project cost (EUR): 166760.0
EU funding (EUR): 149723.0
Participants: 1
Project status: CLOSED

The main objective of the proposed work is to develop a high rate, compact and low cost quantum random number generator (QRNG), i.e. a physical device based on the intrinsic randomness of quantum observables designed to generate a sequence of numbers or symbols that lack any pattern. The device will outperform current state of the art random number generators and will be the choice, among other applications, for increasing security of current (10 and 40Gb/s) and future (100Gb/s) optical telecommunication networks. Specific objectives include: (i) scaling up of the QRNG rate from the current laboratory demonstrator rate (1Gb/s) to at least 10 Gb/s, possibly 100 Gb/s; (ii) optical, mechanical and electronic integration into a package of 15x10x2cm3; (iii) development of a test plan in accordance also to the market and potential customers standards and requirements (iv) reduction of direct costs, in particular bill of materials below 250€; (v) commercial exploitation, including IP, market study, competitiveness of the product, technology transfer and spin-off evaluation. The proposed QRNG device operates on the field within a single mode of a semiconductor diode laser. Taking advantage of the randomness nature of vacuum fluctuations, a stream of phase-randomized, nearly identical optical pulses is produced. Interference of subsequent pulses converts the phase randomness into strong amplitude modulation of random intensity, which is directly detected and digitized. The device utilizes commercially available optical and electronic components, including standard laser sources and photodetectors, thus offering a low cost and integrated solution for the hardware implementation. These will be essential to generate market prospects in several areas, ranging from lottery and gambling to secure communications and scientific calculations. Initial estimates indicate an addressable market at around several tens of M€, with the potential to become several hundreds in the future.

Keywords: 209267
Biogenesis of lipid droplets and lipid homeostasis (DROPFAT)

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: Spain
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2018-01-31
Duration (months): 60.0
Total project cost (EUR): 1475282.0
EU funding (EUR): 1475282.0
Participants: 2
Project status: CLOSED

Organisms and cells face a myriad of environmental changes with periods of nutrient surplus and shortage. It is therefore not surprising that in all kingdoms of life, cells have evolved the means to store energy and thereby minimize the effects of environmental fluctuations. While the capability for energy storage has obvious advantages, deregulated energy accumulation can also be detrimental and is the hallmark of many diseases such as obesity. In most cells energy is stored as neutral lipids in a dedicated cellular compartment, the lipid droplets (LDs). LDs are found in virtually every eukaryotic cell and play a central role in cellular lipid and energy metabolism. Despite their ubiquitous presence and importance, the physiology of LDs is poorly understood. LDs are composed of a single lipid layer and therefore distinct from all other cellular compartments. How do LDs originate at the endoplasmic reticulum (ER) and what is the machinery involved? How is the size, number and the storage capacity of the LDs regulated? How are specific proteins and lipids targeted to LDs? Addressing these questions is fundamental for understanding the “life cycle” of LDs and for a global picture of the cellular energy homeostasis. The main goal of this proposal is to reveal the molecular mechanisms controlling neutral lipid dynamics and their storage in LDs. We will focus specifically on the role of the endoplasmic reticulum in the biogenesis of LDs. First, we will identify the ER protein complexes required for LD formation and regulation. Second, we will develop an assay to dissect the targeting of proteins to LDs. Finally, we will develop a cell-free system that recapitulates the biogenesis of LDs in vitro. Altogether, our strategy constitutes a systematic, in-depth analysis of LD dynamics and will lead to significant insight on the mechanisms of cellular energy storage. Our findings will likely offer a better understanding of human pathologies such as obesity and lipodistrophies

Keywords: endoplasmic reticulum,lipid droplet,neutral lipid metabolism
Production of Cyclic Carbonates from CO2 using Renewable Feedstocks (CYCLICCO2R)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Materials
Action type: Collaborative project
Countries involved: Netherlands,Norway,Netherlands,United Kingdom,Germany,Netherlands,Germany,United Kingdom,Iceland
Call:  (FP7-NMP-2012-SMALL-6, 2012)
Start date: 2013-01-01
End date: 2016-12-31
Duration (months): 48.0
Total project cost (EUR): 5254690.8
EU funding (EUR): 3851934.0
Participants: 10
Project status: CLOSED

The concept of CyclicCO2R is to create a process that removes the dependency on fossil fuel and increases the energy efficiency to create a net CO2 uptake in the production of cyclic carbonates. This objective will be reached by basing the process on the use of renewables and CO2 in the production of cyclic carbonates. Two routes will be explored: 1) production of glycerol carbonate methacrylate from epichlorohydrin and CO2 and 2) production of propylene carbonate from propylene oxide and propylene glycol with CO2 The focus will be on: 1) Development of the optimal catalyst-process combination both in activity, catalyst recoverability and optimal immobilization technique; 2) Intensification of the reactions in a flow reactor focusing on energy efficiency and increased product yields; 3) Creating a miniplant scale process which starts with the renewable raw materials and CO2 and produces cyclic carbonates; 4) Completion of designs and engineering of a scaled-up process integrated with a chemicals plant so that the developed technology is directly transferrable to industry; Furthermore the feasibility of using CO2 in combination with water to produce intermediates of the cyclic carbonate production directly will be evaluated (currently photocatalytic and electrocatalytic processes with a high selectivity, but a low yield). If this is possible, in the future, the production of cyclic carbonates from CO2, water and energy (available at the same location) will become possible. It will increase the CO2 utilisation in the production of cyclic carbonates. The proposal will create a new industrial process in which renewables and CO2 are used to create value products and reduce GHG emissions.

Keywords: cyclic carbonates,co2,renewables,process intensification,flow chemistry,glycerol,glycerol carbonate
Protein Misfolding: Prion-like Propagation and Cure. Implications for Neurodegenerative Diseases. (PROCUREPM)

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: United Kingdom
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2019-01-31
Duration (months): 72.0
Total project cost (EUR): 1431408.0
EU funding (EUR): 1431408.0
Participants: 2
Project status: CLOSED

My long-term goal is to understand, how misfolded proteins, associated with the pathogenesis of most neurodegenerative diseases, propagate in a prion-like manner (i) and to identify strategies that could lead to cure protein misfolding (ii). (i) We have recently discovered that mutant SOD1 aggregates, associated with amyotrophic lateral sclerosis, penetrate inside cells and replicate their misfolded state indefinitely, just like prions. Using our robust cell-based system, we will identify the mechanisms underlying the prion-like propagation of misfolded proteins using unbiased biochemical approaches combined with siRNA screens (Aim 1). (ii) We have discovered a novel and selective way to rescue cells from protein misfolding stress. We have identified a small molecule, guanabenz, which binds to a regulatory subunit of protein phosphatase 1, PPP1R15A/GADD34, selectively disrupting the stress-induced dephosphorylation of the alpha subunit of translation initiation factor 2 (eIF2 alpha). Without affecting the related PPP1R15B-phosphatase complex and constitutive protein synthesis, guanabenz prolongs eIF2 alpha phosphorylation in stressed cells, thereby adjusting the protein production rates to levels manageable by available chaperones. This favors protein folding and thereby rescues cells from protein misfolding stress. This suggests that inhibition of PPP1R15A could ameliorate protein misfolding diseases. We will test this attractive possibility (Aim 2). Having provided the proof of principle that serine/threonine phosphatases are drug targets, we aim to investigate the detailed molecular mechanism by which guanabenz selectively inhibits PPP1R15A/GADD34, using a combination of biophysical and structural approaches (Aim 3). In addition, we will develop assays to identify other selective serine/threonine phosphatase inhibitors (Aim 4). Ultimately, the knowledge emanating from our work will serve to ameliorate human health and disease.

Keywords: protein folding. protein misfolding. stress responses. protein quality control. protein aggregation. protein misfolding diseases. protein phosphatase 1.
Compensatory Evolution and Epistasis in Multidrug-resistant Mycobacterium tuberculosis (EVODRTB)

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: Switzerland
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-04-01
End date: 2019-03-31
Duration (months): 72.0
Total project cost (EUR): 1498614.0
EU funding (EUR): 1498614.0
Participants: 1
Project status: CLOSED

Multidrug-resistant bacteria are a global threat to public health and the economy. Studies in model organisms suggest compensatory evolution and epistatic interactions between drug resistance-conferring mutations are important drivers of drug resistance. However, the relevance of these factors for the emergence and transmission of human pathogenic bacteria has not been established. To bridge the gap between laboratory experimentation and epidemiology, I propose a multidisciplinary approach focusing on Mycobacterium tuberculosis, the etiologic agent of human tuberculosis (TB). Specifically, I shall combine experimental evolution and fitness assays in vitro and in human macrophages with comparative genome sequencing, RNAseq-based transcriptomics, and population-based molecular epidemiology to: 1) Identify and characterize compensatory mutations in M. tuberculosis resistant to rifampicin, streptomycin, and ofloxacin; 2) Detect epistasis between drug resistance-conferring mutations in different strain genetic backgrounds; 3) Investigate the effect of drug resistance-conferring mutations, compensatory mutations, and their epistatic interactions on the M. tuberculosis transcriptome. The strength of my approach lies in the integration of an experimentally tractable model system (Mycobacterium smegmatis) with targeted validation experiments in clinically relevant M. tuberculosis, and comprehensive molecular epidemiological data collected prospectively in Georgia, a country with a high-burden of multidrug-resistant TB. Through its multidisciplinary nature, this project will simultaneously test predictions from ecological theory and experimental models, generate new insights into the biology and epidemiology of multidrug-resistant TB, and ultimately contribute to the control of one of humankind’s most important infectious diseases.

Keywords: antimicrobial resistance,evolution,fitness,molecular epidemiology,comparative genomics,rnaseq
Systems biology meets evolutionary theory: modeling the genetics and adaptation of complex traits (EVOSYSBIO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-09-01
End date: 2017-08-31
Duration (months): 60.0
Total project cost (EUR): 1452478.0
EU funding (EUR): 1452478.0
Participants: 1
Project status: CLOSED

As we learn more about the mechanisms of development, it remains a challenge to understand the relationship between molecular processes and functional characteristics of the organism. The complexity of the networks that link genes and phenotypes is nearly ignored by evolutionary theory, which builds on simple phenomenological models of the genotype-phenotype relationship. These models treat development as a black box, leaving mainstream evolutionary theory ill-equipped to explain how molecular mechanisms evolve. In order to resolve this problem, the current proposal develops a framework for understanding the evolution of complex traits and their genetic basis, integrating methods from systems biology and evolutionary genetics. This novel strategy is first applied to bacterial chemotaxis, a prototype for studying the molecular basis of emergent behavior and its response to selection. A second project examines evolutionary diversification by modeling the origin of distinct ecotypes observed in evolution experiments with Escherichia coli. In both cases, I employ systems-biology models to reconstruct the relationship between molecular mechanisms and phenotypic characters under selection and then apply population-genetic techniques to study how populations evolve on these landscapes. The work on microbial model systems is complemented by conceptual analyses that examine how sexual populations evolve on complex adaptive landscapes. I will study whether higher organisms differ from bacteria in the way they realize evolutionary innovations and whether the high rate of recombination in sexual species has an effect on the structure of molecular interactions. This research will also clarify what signatures of selection are likely to be found in molecular networks. A final research aim is to delineate under what conditions phenotypic evolution can be studied without knowledge of molecular details, which is still the common situation in evolutionary biology.

Keywords: evolutionary systems biology,genotype-phenotype map,development,molecular networks,complex adaptive systems,computational genetics,evolutionary genetics
Reclamation of Gallium, Indium and Rare-Earth Elements from Photovoltaics, Solid-State Lighting and Electronics Waste (RECLAIM)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Integration
Action type: Collaborative project
Countries involved: Netherlands,Spain,Spain,Austria,Romania,Sweden,Italy,Netherlands,Netherlands,Spain
Call:  (FP7-NMP-2012-SME-6, 2012)
Start date: 2013-01-01
End date: 2016-12-31
Duration (months): 48.0
Total project cost (EUR): 7072109.2
EU funding (EUR): 4715525.0
Participants: 12
Project status: CLOSED

Prospective global supply and demand for gallium, indium and other key metals show an increasing discrepancy, amongst others due to the explosive growth of green technologies such as photovoltaics (PV) and solid-state lighting (SSL). While their primary production is highly controlled by a few countries, recycling systems to reclaim these materials from discarded products are not yet in place. This makes Europe susceptible for the provision of materials that are crucial for meeting policies on energy saving and renewability, as well as challenges the further development of the concerned industrial sectors. Hence there is a strong need to establish recycling systems for PV, SSL and other electronic waste and capitalise on these as yet unexploited and growing deposits of key materials. The bottlenecks are in the disconnection and sorting of the parts with the targeted materials from the waste and in the release, concentration and purification of the reclaimed metals. More in particular, the concerned materials tend to be used as compounds (gallium arsenide, gallium nitride, indium tin oxide) rather than in their elemental form and to be applied as thin layers on substrates in overall very low amounts. Objectives of the proposed project are (1) technological solutions that relieve current bottlenecks in the recycling of gallium, indium and rare-earth elements, and (2) demonstration of their application potential by means of a pilot implementation in an industrial setting. The project is to result in separation methods for electronic assemblies that reduce manual work (>80% automation) as well as in subsequent recovery methods that yield recycled materials of commercial-grade quality (>99-99.99%, depending on the element), apt to fit an industrial context and being environmentally compliant. To this end, (thermal) disconnection methods, part recognition methods and hydrometallurgical refining processes will be developed. Impact assessments will also be included.

Keywords: recycling,gallium,indium,rare-earth elements