Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Project PEA (Photosynthesis and Earth Atmospheres): Investigating the effect of evolutionary adaptation to high atmospheric carbon dioxide concentrations in fossil and living plants (PROJECT PEA)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Italy
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-06-01
End date: 2013-05-31
Duration (months): 24.0
Total project cost (EUR): 181084.0
EU funding (EUR): 181084.0
Participants: 1
Project status: CLOSED

Photosynthesis is of critical importance to biodiversity, food security and society within the context of current climate change. The photosynthetic responses of plants to rising atmospheric CO2 have been studied in experiments where CO2 is artificially enriched to predicted levels. However, these experiments involve plants adapted to current “low” ambient levels of ~380ppm CO2, and do not incorporate consideration of plant evolutionary adaptation of photosynthesis, where the physiology of plants adjust to long-term incremental CO2 rises. Plants growing around volcanic CO2 degassing vents possess an evolutionary adaptation to “high” atmospheric CO2 and display markedly different responses than plants adapted to lower ambient CO2. Plants adapted to “high” CO2 exhibit pronounced photosynthetic rates, no down-regulation of photosynthetic physiology and maintenance of transpiration rates – all important parameters for coupled atmosphere-biosphere models of climate, vegetation and carbon sequestration responses to aid management and mitigation of future climate change. These evolutionary responses to CO2 are also present in the plant fossil record over timescales of millions of years. The stomata of fossil plants are used to reconstruct past atmospheric levels of CO2 in the study of previous global-warming events that provide important climate/biodiversity indicators for the current global-warming crisis. The use of living plants adapted to both “high” and “low” atmospheric CO2, in comparative physiology/morphology studies under elevated CO2, will provide much needed data on likely plant responses to rising CO2 and those of plant fossils through earth history. This will place Europe at the forefront of plant evolution and palaeoclimatic research; linking two European research institutions (IBIMET, Italy and UCD, Ireland) in the European Research Area to create a platform for European Research Excellence and competitiveness.

Keywords: photosynthesis,plant evolution,climate change,stomata,volcanic degassing vents,fossil plants,palaeo-co2,carbon dioxide
Interrogating macromolecular assemblies by using fragment-based small molecule approaches: The multiprotein von Hippel Lindau-E3 ubiquitin ligase complex. (PVHL-CRL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-03-01
End date: 2013-02-28
Duration (months): 24.0
Total project cost (EUR): 199549.6
EU funding (EUR): 199549.6
Participants: 1
Project status: CLOSED

Most proteins exert their biological function by interacting with other proteins in complex macromolecular assemblies. Modulating protein:protein interactions (PPIs) using small drug-like molecules has the potential to unlock new horizons for chemical biology and developing novel therapeutics. However, this task has proven difficult because of the diverse, complex and dynamic nature of PPI interfaces. This project aims at investigating the plasticity and druggability of PPI interfaces within multi-protein assemblies by an innovative approach combining fragment-based chemical tools, biophysical and structural methods, using the von Hippel Lindau (pVHL)-Cullin Ring type E3 ubiquitin ligase (CRL) complex as a model system. The pVHL-CRL is responsible for the recognition, poly-ubiquitylation and subsequent degradation of HIF-1α, a key regulator of cellular oxygen sensing. This interaction is impaired during the hypoxic proliferation of tumours and as a result of pVHL mutations in the VHL disease, a human syndrome predisposing to cancer. By characterizing the binding of fragments to wild-type and disease mutants of this multi-subunit complex, this project will provide novel insights on the important features for small molecule targeting to PPI interfaces and on how to modulate PPIs not only directly by targeting the interaction hot spots, but also indirectly e.g. through binding to distant allosteric sites. Such knowledge will also be harnessed towards developing novel drug like small molecules, by applying NMR techniques for the detection of fragment binding to adjacent sites and developing dynamic combinatorial X-ray crystallography to in situ linking of these fragments. By improving our understanding of how to discover small molecule enhancers/stabilizers as well as inhibitors/disruptors of PPIs this fellowship will contribute to European research efforts on understanding and targeting protein:protein complexes in chemical biology and drug discovery.

Keywords: protein:protein interactions,multi-protein complex,fragment based and structure based drug discovery,von hippel-lindau protein (pvhl),cullin ringe type e3 ubiquitin ligases (crls)
Characterisation of early cellular and molecular alterations leading to inflammation and HCC using a mouse model with liver cell-specific NEMO ablation (KONDEVANS2010)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2012-02-06
End date: 2014-02-05
Duration (months): 24.0
Total project cost (EUR): 168863.2
EU funding (EUR): 168863.2
Participants: 1
Project status: CLOSED

Chronic liver inflammation has been shown to promote hepatocellular carcinoma (HCC). However, the initial cellular and molecular events that trigger the inflammation are largely unknown. The proposed study will provide a detailed characterisation of cellular processes that need to be deregulated in liver cells to cause inflammation. For this purpose, a genetic mouse model that closely reproduces all the stages of inflammation-related HCC will be used. This mouse exhibits a Liver Parenchymal Cell specific NEMO ablation (NEMOLPC-KO), the regulatory subunit of the IKK complex that activates NF-kB signalling. The two main goals of the proposed project are to a) unravel early cellular and molecular alterations in the liver cells of NEMOLPC-KO mice, and distinguish these resulting from a cell-autonomous effect of NEMO deletion from those resulting from a non-cell autonomous effect due to the inflammatory microenvironment and b) distinguish between NF-kB-dependent and independent functions of the NEMO/IKK complex in liver homeostasis. Two experimental strategies will be used to achieve these goals. The first is a targeted examination of specific cellular processes that could be implicated in the development of liver inflammation, such as the mitochondrial functions, ER stress, autophagy, and p62 functions. A combination of mouse genetics with cutting-edge microscopy and other cell biology techniques will be employed. The second involves high-throughput approaches, such as gene expression microarray, that will help distinguishing between the above-mentioned NEMO functions. The scientific impact of this study will be to define early cellular changes can disrupt liver cell homeostasis resulting in human liver inflammatory diseases, thus helping in development of new therapeutic approaches. Finally, the project will greatly benefit the applicant’s professional maturity that is important for pursuing an independent research career.

Keywords: mouse molecular genetics,cell biology,liver inflammation,hcc,non-alcoholic fatty liver disease,tissue homeostasis,nemo,oxidative stress,nf-kb-dependent and independent functions,ikk complex
The ß-scorpion toxin binding site as a potential target for new insecticides (ß-TOXIN INSECTICIDE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-08-01
End date: 2013-07-31
Duration (months): 24.0
Total project cost (EUR): 217824.2
EU funding (EUR): 217824.2
Participants: 1
Project status: CLOSED

Effective pest control is essential for human health, prosperity and food security. The development of insecticide resistance threatens agriculture and health programmes, where insect vectors spread life-threatening diseases such as malaria. Therefore there is a continuous need for new, effective and environmentally-friendly insecticides against novel molecular targets in order to circumvent resistance mechanisms. Members of the beta-scorpion toxin family display an extraordinary species-selective toxicity towards insects. beta-toxins bind with voltage-gated sodium channels but the binding determinants of the beta-toxin receptor site remain to be fully elucidated. In particular the residues which underpin the species-selectivity of toxin binding are not determined yet. I propose to elucidate the binding interactions of the insect-specific BmK IT1 beta-scorpion toxin with its receptor site on the extracellular linkers of the insect domain II voltage-sensor. I plan to use a recently-developed chimeric strategy in a combinatory mutagenesis, electrophysiology and 3D modelling approach in order to generate a description of toxin binding. I have expertise in molecular biology, computer modelling and ion channel expression. To complete my skill set as an ion channel researcher, I require practical electrophysiology experience. With this grant, I will pursue three goals: 1. Training in electrophysiology techniques. 2. Application of these techniques to study BmK IT1 binding with insect receptor site and thereby answering three questions: a: Which sodium channel function is modified by BmK IT1? b: Where on the voltage-sensor paddle does BmK IT bind? c: Does the insect S1-S2 linker modify BmK IT binding? The third goal is to develop a 3D molecular model of BmK IT interaction with the insect receptor site, thereby providing valuable structural information to enable pharmacophore modelling aiding novel insecticide design.

Keywords: natural sciences,sodium channels,insecticide,patch-clamp,scorpion toxin,chimera,toxin expression,voltage sensor,mutagenesis,molecular modelling,automated docking
Application of a Novel Magnesium-Lithium Dual Isotopic Tracer to Biogeochemical Cycles in the Soil Critical Zone (ISOCRIT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2010-IIF, 2010)
Start date: 2011-08-01
End date: 2013-07-31
Duration (months): 24.0
Total project cost (EUR): 210092.8
EU funding (EUR): 210092.8
Participants: 1
Project status: CLOSED

Chemical weathering exerts a key control on global CO2 cycles and ocean chemistry. Magnesium is a particularly important aspect of seawater chemistry, given that it controls the nature of carbonate precipitation is important tool in the reconstruction of past ocean temperatures. Stable isotopic tracers are increasingly being used to identify sources of Mg and other constituents in rivers and oceans and in marine sediments and sedimentary rocks to deduce paleoclimates, ancient ocean chemistry and circulation, and other aspects of Earth’s history. However these interpretations are entirely dependent on the processes that may fractionate the isotopes during mineral weathering and (bio)geochemical cycling. This proposal seeks to develop a novel biogeochemical multi-tracer using Mg and Li isotopes and apply it to test and interrogate the hypothesis that the isotopic composition of Mg in rivers is influenced by chemical weathering reactions in catchment soils. In particular, it seeks to understand processes in soils, the ultimate reactor in which the riverine flux to the oceans is determined. As an intensive case study, the isotopic multi-tracer technique will be applied to a large set of natural samples previously obtained from the Luquillo Mountains in Puerto Rico. This dataset will be used to demonstrate the potential of the multi-tracer technique and to move forward the models of biogeochemical mineral nutrient cycling that I am developing for the Luquillo Critical Zone Observatory (LCZO). The Mg-Li multi-tracer will also be applied on a global scale, by analyzing a large suite of soil samples from a variety of climates, latitudes, and rock types, which are currently archived by Professor Vance in Bristol.

Keywords: magnesium,lithium,global cycles,biogeochemistry,weathering,co2,isotopes,tropical,soils
Enantioselective Isocyanoacetate Addition Reactions under Cooperative Base and Lewis Acid Catalysis (ENISOCOC)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-03-01
End date: 2013-02-28
Duration (months): 24.0
Total project cost (EUR): 200549.6
EU funding (EUR): 200549.6
Participants: 1
Project status: CLOSED

Enantioselective Isocyanoacetate Addition Reactions under Cooperative Base and Lewis Acid Catalysis. Enantiomerically pure substances with the capacity to simultaneously activate two reagents towards one another, offer numerous opportunities for the discovery of powerful, asymmetric bond forming reactions. When a compound possesses a combination of Brønsted (or Lewis) basic and Lewis acidic sites, has a well-defined chiral pocket constructed around a fairly rigid skeleton and appropriate distances between the two activating groups, the templating of a pronucleophile (NuH) and an electrophile via a ternary complex can lead to excellent levels of enantio- and diastereocontrol in efficient addition reactions at low catalyst loadings. The design and synthesis of new, readily accessible catalytic systems plays a pivotal role in this field of research allowing the discovery of useful synthetic pathways, rapid optimization of the ligand canopy and a better understanding of the mechanism and origins of stereocontrol. During this Fellowship we wish to develop new and synthetically powerful enantioselective inter- and intramolecular addition reaction of isocyanoacetate pronucleophiles under cooperative base and Lewis acid catalysis. In particular we wish to investigate the addition chemistry of imines and electron deficient double bonds, as well as intramolecular additions to pendant alkyne functionality, using novel aminophosphine precatalyst/transition metal ion combinations. Not only will these reactions constitute important developments in the field but the product structures are often biologically relevant, thus lending the chemistry to important synthetic applications.

Keywords: physical sciences,organic chemistry,enantioselective organocatalysis,addition reactions,base and lewis acid cooperative catalyst,molecular modeling studies,bioactive natural produ
Role of descending hippocampal outputs in anxiety studied using a novel pharmaco-genetic efferent inhibition tool (HIPPOPROJECTION)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-04-01
End date: 2013-03-31
Duration (months): 24.0
Total project cost (EUR): 181084.0
EU funding (EUR): 181084.0
Participants: 1
Project status: CLOSED

The brain structures and neural circuits regulating anxiety behavior are poorly understood. The hippocampus contribute to anxiety via its role in the behavioral inhibition system and descending outputs via the fornix to the septum and frontal cortex are thought to be critical to this modulating effect. However, it is not clear what the contributions of septal and frontal cortical outputs are to anxiety because, until now, no manipulations were available to selectively inhibit these pathways. Here we propose to develop a pharmacogenetic inhibition technology to selectively manipulate hippocampal efferents and determine the contribution of specific hippocampal outputs to anxiety behavior. The host laboratory has already developed a method for the inhibition of genetically defined cell populations in behaving mice. During the first part of the fellowship, I will develop a modified version of this technology based on axonally transported inhibitory GPCRs that allows for the pharmacological suppression of neurotransmitter release in genetically defined synapses. Later, I will use this technology to examine the behavioral effects of blocking selected hippocampal outputs, with a primary focus on hippocampus-frontal cortex projections. The expectation is that the development and validation of this technology will open up a novel approach to study brain function.

Keywords: hippocampus,frontal cortex,efferent,anxiety,mouse.
Molecular genetic dissection of chromosomal fragile sites (FRA-SITE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Denmark
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-03-01
End date: 2013-02-28
Duration (months): 24.0
Total project cost (EUR): 229627.2
EU funding (EUR): 229627.2
Participants: 1
Project status: CLOSED

Chromosomal fragile sites (CFS) are naturally occurring hot-spots for DNA breakage. CFS are frequent breakpoints for chromosome translocations, prone to expansion of repetitive elements and susceptible to other types of genetic instability. Chromosomal fragile sites have therefore been linked to several types of cancer as well as to neurological disorders such as obsessive-compulsive disorder, type I bipolar disorder, schizophrenia and Fragile X syndrome. In most cases, CFS are cytogenetically defined megabase regions of the genome and the underlying molecular mechanisms and genetic requirements for fragile site instability are unknown. This is largely due to the difficulty of genetic manipulation of these elements in human cells. In order to investigate the molecular mechanisms and genetic requirements that control fragile site stability, we will take advantage of two genetic model systems, the yeast Saccharomyces cerevisiae and the vertebrate DT40 cell line (Gallus gallus), which allow for genome-wide screens and genetic manipulation to test specific hypotheses regarding chromosomal fragile sites.The goal of this project is to perform a molecular, genetic and cell biological analysis of CFS. Specifically, the aims of this project are (i) to identify the genetic requirements for fragile site expression (ii) to isolate and characterize proteins that bind to fragile sites and (iii) to investigate the impact of transcription, replication and chromatin structure on fragile site expression.

Keywords: natural sciences,cancer,molecular biology,cell biology,dna repair,chromosome stability
A NOvel Architecture for a photonics LIquid State machine (NOVALIS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-07-01
End date: 2013-06-30
Duration (months): 24.0
Total project cost (EUR): 167065.6
EU funding (EUR): 167065.6
Participants: 1
Project status: CLOSED

Reservoir computing represents a new paradigm in information processing, based on the insight that computational power can emerge from a system’s complexity. The project’s objective is to develop a novel photonic approach to reservoir computing. The experimental scheme will implement the concept of a liquid state machine (LSM), a sub-category in the neuro-inspired framework of reservoir computing. It has been shown that LSMs posses universal and highly efficient computational properties. Experimental realizations of liquid state computing are scarce, regardless of highly promising simulations. This project’s goal is a new photonic approach towards a LSM: a VCSEL array will be embedded in a cavity, delay-coupling several laser diodes. Consequently, a complex network can form, consisting of the connections between individual diodes. This delay network acts as the reservoir. Compared to individually coupled elements this approach has major advantages, comprising the chance of truly parallel computing, scalability and flexibility. Starting with a small scale demonstration using few coupled lasers, the experiment will extend to VCSEL arrays with potentially many lasers. Spatial filtering inside the cavity might offer a practical implementation of plasticity and network motif concepts, enabling a dynamical adaption of coupling strength and topology. The experienced researcher will extend his background in information processing concepts. The ER will be trained in these novel concepts and in experimental techniques related to photonics technologies and complex systems. This is complemented by an attractive training program of secondary skills. Therefore, the proposed project adds to a highly competitive and promising profile, supporting a future position of professional maturity. Both, host organization (IFISC) and mentoring researcher (Prof. Fischer) provide a unique environment for realizing the proposed project, as well as supporting the experienced researcher.

Keywords: physical sciences,technological sciences,reservoir computing,parallel computing,liquid state machine,optical computing,neuro-inspired computing