Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Determination of the structure of the pathological neuroserpin polymer and development of an intrabody strategy to prevent disease-associated inclusions in cell and animal models of disease (SERPINOPATHIES)

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,United Kingdom
Call:  (FP7-PEOPLE-2011-IEF, 2011)
Start date: 2013-03-01
End date: 2015-02-28
Duration (months): 24.0
Total project cost (EUR): 200371.8
EU funding (EUR): 200371.8
Participants: 2
Project status: CLOSED

An increasing number of human disorders are recognised to result from the aggregation and tissue deposition of misfolded proteins. This group of diseases has been termed the conformational disorders and comprises such diseases as Alzheimer’s, Huntington’s and Parkinson’s disease as well as the amyloidoses and the serpinopathies. The serpinopathies are characterized by the polymerisation and tissue deposition of mutants of members of the serine protease inhibitor or serpin superfamily of proteins. One of the most striking serpinopathies is familial encephalopathy with neuroserpin inclusion bodies (FENIB) that is caused by one of six naturally occurring point mutations in the neuroserpin gene. Mutant neuroserpin forms ordered polymers that accumulate within the endoplasmic reticulum of neurons, resulting in progressive dementia, with the age of onset of disease being inversely proportional to the rate of polymer formation in vitro and the number of intra-cerebral inclusions. This study will use an anti-polymer monoclonal antibody to (i) define the structure of the pathological neuroserpin polymer and its time-dependent appearance in the ER and (ii) as the basis for an intrabody strategy to prevent the inclusions associated with disease. First, regions of neuroserpin that are exposed upon transition from monomer to polymer will be analyzed by epitope mapping using differential chemical modification and crystallization aided by an antibody-engineered construct. Second, the ability of this anti-polymer monoclonal antibody to prevent pathogenic polymer formation and to impact their intracellular localization pattern will be assessed by co-expression with different neuroserpin mutants in cell and fly models of disease. The protective efficacy in vivo will be addressed by analyzing the locomotor phenotype in flies. If successful, an intracellular antibody based approach may be used to treat the serpinopathies and other ‘gain of function’ conformational diseases.

Keywords: serpinopathies,conformational disorders,neuroserpin,fenib,protein misfolding,neurobiology
Novel Nano-Stabilisation for Green Bioplastic Nanocomposites (NANOSTAB-GB)

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-2011-IEF, 2011)
Start date: 2012-10-01
End date: 2014-05-31
Duration (months): 20.0
Total project cost (EUR): 232339.5
EU funding (EUR): 232339.5
Participants: 1
Project status: CLOSED

The primary focus of NANOSTAB-GB (Novel NanoStabilisation for Green Biopolymer-Nanocomposites) is on developing innovative technology for enhancing processability, performance and durability of sustainable green biopolymer-based nanocomposite materials. The underpinning science is a novel chemical process for the immobilisation of protective agents onto natural nanoscopic-size reinforcing fillers embedded in biodegradable and compostable polymers. The novel chemistry developed here will be technologically relevant and industrially viable for production of durable structured biodegradable nanocomposites with direct involvement (in project and training) of leading European producer. One challenging demand in materials research today is that of the development of advanced materials based on sustainable resources as alternatives to fossil fuel-based materials. Current biopolymer-clay-based nanocomposites have the potential to meeting this demand competitively but only when new technological breakthroughs emerge to overcome major short- and long- term performance problems of stability during high temperature manufacture and in-sevice. The scientific goal of NANOSTAB-GB is to bring about step-change development in a technology platform which is readily scalable by implementing ‘smart’ stabilisation approaches for modifying nanoparticles and building biopolymer-nanoparticle reinforcing networks structured around naturally-occurring, bio- or synthetically- based antioxidants. Results generated will be disseminated globally; the outcome of NANOSTAB-GB addresses directly the EU vision of ‘Knowledge Based Bio Economy’. IP generated will help maintain EU lead on ‘green’ materials and to meeting CO2 emission targets. Above all, it will provide an inspirational training opportunity for a talented fellow with assured successful outcome benefitting both fellow and EU with the emergence of a multi-skilled leader in biomass-based materials research with sustainability at its core.

Keywords: physical sciences,materials engineering,industrial chemistry,biopolymer-nanocomposites,antioxidants and stabilisation,biodegradable nanostructures,multihybrid materials,reactive processing
Molecular characterization of the interaction of β -2 microglobulin with collagen (MCIBC)

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-2011-IEF, 2011)
Start date: 2013-02-01
End date: 2015-01-31
Duration (months): 24.0
Total project cost (EUR): 200371.8
EU funding (EUR): 200371.8
Participants: 1
Project status: CLOSED

β -2 microglobulin (β-2-m) is a 99 residue protein with an immunoglobulin fold. β-2-m is usually found as a part of the major histocompatibility 1 complex. This protein aggregates to form amyloid fibrils in osteoarticular tissues, leading to pathological bone destruction and the condition known as dialysis-related amyloidosis (DRA). The accumulation of β-2-m deposits has been shown to cause arthralgias, destructive osteoarthropaties and carpal tunnel syndrome. The host laboratory has characterized β-2-m amyloid assembly and developed a molecular description of the folding and aggregation mechanisms of β-2-m under relevant conditions, but the factor or factors responsible of the initiation of the aggregation process are still unknown. β-2-m amyloid accumulates in connective tissue, causing the pathological consequences of the disease. Collagen is one of the main components of this tissue and has been proposed to be a possible contributing factor in the initiation of aggregation. Consistent with this, studies with ex vivo amyloid material show that there is a strict association between β-2-m and collagen within joints, while biochemical experiments have revealed tight binding between β-2-m and collagen. This project will focus on the study of the interactions between collagen and β-2-m and its consequences for the formation of amyloid fibrils from a molecular viewpoint. We will study the specificity of interaction of β-2-m with different collagen sequence patterns and the influence of collagen on β-2-m stability, dynamics, and aggregation rate. For this project a complementary set of biophysical techniques, including mass spectroscometry, NMR, fluorescence, infrared spectroscopy and electron microscopy, will be used. The results will facilitate the design of small molecules or nanoparticles (copolimer, dendirmers) directed to interfere with the interaction of β-2-m with collegen as a route toward prevention of β-2-m fibrillization.

Keywords: health sciences,amyloid,beta-2-microglobulin,collagen,dialysis related amyloidosis,nmr,mass spectroscopy,fluorescence spectroscopy
The Catalytic Synthesis of Sulfonamides (SULFONAMIDES)

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-2011-IEF, 2011)
Start date: 2012-09-17
End date: 2014-09-16
Duration (months): 24.0
Total project cost (EUR): 209033.4
EU funding (EUR): 209033.4
Participants: 1
Project status: CLOSED

Sulfonamides are functional groups that feature in a significant number of pharmaceuticals, with applications in a variety of indications. Conventional syntheses of sulfonamides usually involve two or three synthetic operations, and often feature low-yielding steps. The chemistry involved also limits the substrates that can be converted to sulfonamides. This proposal seeks to develop an alternative synthesis of sulfonamides; the proposed synthesis will be achieved in a single operation, employ readily available reagents and substrates, and be conducted under mild conditions. The key to the proposed synthesis is to employ a three-component synthesis involving the catalytic combination of an aryl halide, an amine and sulfur dioxide. Achieving the synthesis in a single operation will have significant advantages in terms of waste production, energy required, as well as the time needed to prepare the desired sulfonamides. These are important considerations for both small scale discovery synthesis, as well as the large scale synthesis of these materials. The developed methodology should also be applicable to the preparation of related sulfonate esters and sulfones. The latter stages of the project will explore the application of the developed method to the synthesis or selected target structures that are difficult to access using conventional methods, and to the synthesis of heterocycles.

Keywords: homogeneous catalysis,organometallic chemistry,organic chemistry
ABDOMINAL SUBCUTANEOUS ADIPOSE TISSUE DEPOTS AND HUMAN METABOLIC PROFILE: A NOVEL CONCEPT OF METABOLIC DYSFUNCTION IN ABDOMINAL OBESITY (SAT-IMG)

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-2011-IEF, 2011)
Start date: 2012-06-01
End date: 2015-04-02
Duration (months): 24.0
Total project cost (EUR): 209033.4
EU funding (EUR): 209033.4
Participants: 1
Project status: CLOSED

Abdominal obesity is related to a number of adverse health outcomes but the relationships between expansion of certain fat depots and health outcomes, or the mechanisms by which adipose tissue communicates to the rest of the body, are unclear. Abdominal subcutaneous adipose tissue (SAT) is divided into two anatomically and morphologically distinct layers (above and below the Scarpa’s fascia). Preliminary data show that expansion of the deep SAT (dSAT) is strongly related to insulin resistance in a manner nearly identical to that of visceral adipose tissue, while superficial SAT (sSAT) appears to follow the pattern of lower body fat. I will use a range of techniques to characterize morphological and physiological differences between dSAT and sSAT in humans and also explore the potential for genetic regulation of fat layer distribution. I will establish a cohort of 1,000 subjects from Oxford Biobank, in whom the SAT layers will be quantified by ultrasound. The technique will be verified against magnetic resonance imaging. I will interrogate morphological/functional differences between SAT layers by taking ultrasound-guided biopsies. Functional characterization of the tissue will consist of transcriptomic patterns, analysis of tissue the explant secretome and adipocyte differentiation capacity. The host group has recently taken part in the first genome-wide association study searching for genetic variants associated with fat distribution and I will capitalize on this by using the unique SAT layer phenotype (n=1000) in combination with a new SNPchip (Illumina iSELECT to be employed in Oxford Biobank, n=5,000). The new SNPchip is based on largely functional variants derived from the 1,000-genomes project and exome sequences of 11,500 people. This study has the potential to provide the medical community with a new, easy-to-use anthropometric tool with strong relationships to obesity-related health outcomes together with functional annotations of the relevant tissues.

Keywords: endocrinology,diabetology,clinical medicine
Auction and Day-Ahead Markets Spikes (AADAMS)

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-2011-IEF, 2011)
Start date: 2012-09-01
End date: 2014-08-31
Duration (months): 24.0
Total project cost (EUR): 209033.4
EU funding (EUR): 209033.4
Participants: 1
Project status: CLOSED

The on-going restructuring and market design processes for the power sector, with its complex objectives of competition, security and decarbonisation has created a need to understand the drivers of change and the nature of electricity price dynamics. Since electricity is a unique commodity, not easily storable with important implications when balancing supply and demand, any imbalances can cause large and sharp changes in price. Hence, AaDAMS, a project on “Auction and Day—Ahead Markets Spikes”, investigates appropriate modeling, forecasting and risk management techniques for the occurrence of spikes and abnormal price excursions in electricity markets, focusing upon agent specific as well as market level data. AaDAMS has a main objective of understanding abnormal price dynamics observed in wholesale electricity prices looking at the behaviour of generators’ auction offers, as well as related parallel objectives concerning the exercise of market power in the European Electricity Markets, the potential interaction of strategic behaviour with new technology characteristics, such as wind intermittency and the effect of policy interventions in market design on price dynamics.

Keywords: social sciences
Cross-species Transmission History and Evolution in the LIneage of Gammaretroviruses and related Endogenous Retroviruses (C THE LIGER)

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-2011-IEF, 2011)
Start date: 2012-04-01
End date: 2014-03-31
Duration (months): 24.0
Total project cost (EUR): 209033.4
EU funding (EUR): 209033.4
Participants: 1
Project status: CLOSED

Endogenous retroviruses (ERVs) are DNA fragments found dispersed in a wide range of genomes, from invertebrates to mammals, that resemble members of the Retroviridae viral family (termed here exogenous retroviruses or XRVs). Because XRV replication involves integration into the host chromosome, it is generally assumed that ERVs are the result of ancient XRV infections, which have passed into the germ-line of the host and expanded within it. ERVs are classified into three classes, while XRVs are classified into subfamilies and genera. Class-I ERVs and Gammaretroviruses are phylogenetically close. Therefore, Class-I ERVs are suggested to be the million-years archive of the Gammaretrovirus infections. I propose to study the viral and host factors that have affected the cross-species transmission history of Gammaretroviruses by studying the relationships between Gammaretroviruses and Class-I ERVs. I will use a bioinformatics’ approach to mine all the available mammalian genomes and extract all the Class-I ERVs. Then, I will build a phylogenetic tree containing all the available Gammaretroviruses and Class-I ERVs to clarify their relationships. I will use the tree to discriminate between shared invasions and cross-species transmission (CST) events. I will implement statistical and phylogenetic methods to clarify if recombination or integrity of the env gene has enhanced or suppressed CST, respectively. I will also look at the protein receptors known to be used by some Gammaretroviruses and correlate their presence and phylogeny in the hosts with the CST events. Moreover, I will look the development of innate antiretroviral resistance mechanisms in the phylogeny of hosts and correlate this with the presence of Class-I ERVs or Gammaretroviruses. Finally, I will study the adaptation that has occurred following the CST events. The project will provide insights into how retroviruses move between hosts, a phenomenon with important Public Health implications.

Keywords: class-i endogenous retroviruses,cross-species transmission,gammaretroviruses
Biotechnological exploitation of Pseudomonas putida: Lego-lizing and refactoring central metabolic blocks through rational genome engineering (ALLEGRO)

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: Spain
Call:  (FP7-PEOPLE-2011-IIF, 2011)
Start date: 2013-02-01
End date: 2015-01-31
Duration (months): 24.0
Total project cost (EUR): 168896.4
EU funding (EUR): 168896.4
Participants: 1
Project status: CLOSED

Pseudomonads include a diverse set of bacteria with metabolic versatility and genetic plasticity that enable their survival in a broad range of environments. Many members of this family are able to both degrade toxic compounds and efficiently produce high value bioproducts, and they are of interest for bioremediation endeavors as well as in bulk production of biochemicals. The present project aims at undertaking a deep genetic and metabolic engineering of Pseudomonas putida KT2440 in order to develop this strain as a biological chassis of reference for genetic and metabolic (re-)programming of bacterial catalysts à la carte. This comprises not only a fundamental (Systems Biology) inspection of P. putida, but also its streamlining into an useful catalytic vehicle for an extensive range of biotechnological applications through rational, systemic refactoring of its versatile metabolic pathways and its stress-resistance abilities. In particular, the objectives of this work include: [1] rational construction of P. putida strains in which the chromosome has been edited and deleted of most unnecessary genomic elements, [2] introduction and optimization of an efficient glycolytic catabolic pathway in thereby obtained strains, and [3] strengthening the stress resistance of these P. putida chasses by genetic outsourcing of oxidative stress-tolerance functions from Deinococcus radiodurans. Using state-of-the art methodologies, these heavily refactored bacterial constructs will be subject to a wide variety of physiological, metabolic, and genetic analysis under various physiological regimes in order to ascertain and quantify the interplay between physicochemical stress and catalytic efficiency. By undertaking these tasks, robust scaffolds for designing biocatalysts with enhanced performance under operating conditions will be obtained, with relevant information about some of their basic metabolic and genetic properties as a sound knowledge base.

Keywords: natural sciences - pseudomonas putida - synthetic biology - systems biotechnology - genome editing - chassis - glucose metabolism - stress resistance - metabolic flux analysis
Gut Symbiomes of Fungus-growing Ants (GUTS)

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-2011-IEF, 2011)
Start date: 2012-06-01
End date: 2014-05-31
Duration (months): 24.0
Total project cost (EUR): 228082.2
EU funding (EUR): 228082.2
Participants: 1
Project status: CLOSED

Symbiosis is the close and long-term interaction between different biological species. Insects are among the best model systems for studying symbioses as their immune systems appear to be relatively tolerant to invasion and their niches are often so specialized that microbial symbionts can satisfy important metabolic needs. Laboratories across the world often specialize either in the molecular biology of host-symbiont interactions in specific insect models, or in the evolutionary biology of parasitic or mutualistic symbioses taking a broader approach. This proposal is meant to build bridges between these domains, by applying advanced molecular methods to resolve fundamental evolutionary questions of symbiosis in a social insect model system. My research will focus on an almost completely unknown component of the symbiosis between attine ants and their fungus-gardens: the bacterial communities in the guts of these ants that likely fulfill complementary roles in the symbiosis. Objectives are to identify these bacteria, to localize them when they are tissue-specific, and to compare their functional roles across several attine genera that represent different stages of advancement of the symbiosis. I will use qPCR, FISH and TEM to identify putative symbionts, metatranscriptomic techniques to characterize the cumulative bacterial genes that are expressed in the ant guts, and qRT-PCR and RNAi to clarify some of the functional roles of ant and microbial genes that are expressed in the guts. The research that I propose is highly multi-disciplinary, as it combines a wide range of state-of-the-art molecular techniques with conceptual hypotheses from social evolution theory. This combination is feasible because my training in molecular microbiology of fruit-fly and aphid symbionts is combined with the renowned expertise of my host in the evolutionary biology of attine fungus-growing ants. The work proposed will be facilitated by annotated genomes of these ants being available.

Keywords: symbiosis,bacteria,endosymbionts,leaf-cutting ants,leucoagaricus,social evolution,molecular microbiology,metatranscriptomics,evolutionary biology,biodiversity characterisation,entomology