Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Self-Assembly in Confined Space (SACS)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Nanosciences and Nanotechnologies
Action type: Collaborative project
Countries involved: Belgium,Spain,Portugal,France,Belgium,Italy,Netherlands,Portugal,Norway
Call:  (FP7-NMP-2012-SMALL-6, 2012)
Start date: 2012-11-01
End date: 2016-10-31
Duration (months): 48.0
Total project cost (EUR): 4550049.0
EU funding (EUR): 3500000.0
Participants: 11
Project status: CLOSED

Supramolecular chemistry studies chemistry beyond individual molecules, where molecules or macromolecules form larger entities by spontaneous self-assembly or by self-organisation. The resulting supramolecular architectures are held together by covalent bonds and a variety of non-covalent intermolecular interactions (hydrogen bonding, metal coordination, hydrophobic interactions etc). Spatially, the supramolecular systems can extend from a few nm to micron size or beyond, in 1, 2 or 3 dimensions, with hierarchical structures containing organisation at distinct characteristic length scales. Consequently, one can control and guide not only the chemical properties of supramolecular systems, such as adsorption affinity, reactivity or catalytic activity, but also the physical properties (mechanical, electrical, optical etc.) with spatial resolution, at different length scales and in different directions. Therefore, supramolecular systems have a potential functionality which tremendously surpasses the scope of classical molecular systems in the liquid state, or of classical porous solids. This potential functionality encompasses the type and number of functions which can simultaneously be fulfilled, as well as the range of viable operating conditions. While the variety of „functions‟ for supramolecular systems is only limited by the imagination of the supramolecular chemist, SACS focuses on the formation, via self assembly, of functional structures in restricted or controlled space to gain new properties resulting from the confinement and to enable the formation of assemblies with controlled geometries as well as size and shape and outstanding properties.

Keywords: luminesence,self-assembly,zeolites,carbon nanotubes,mof,catalysis
The role of nuclear gene flow in the evolutionary history of Pleistocene mammals (GENEFLOW)

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: Germany,United Kingdom
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-12-01
End date: 2017-11-30
Duration (months): 60.0
Total project cost (EUR): 1449380.0
EU funding (EUR): 1449380.0
Participants: 2
Project status: CLOSED

How important are environmental barriers between species and populations now and in the future? Currently, environmental barriers to movement across habitats that have persisted since the last ice age are breaking down, resulting in gene flow among previously isolated populations and even hybridization between species. What are the consequences of this gene flow? Local genetic adaptations to the specific conditions of a habitat are though to be threatened when gene flow occurs, but we know little about the long-term evolutionary effects such events have on species. Recent ancient DNA work on polar and brown bears even suggests that gene flow may be beneficial, rather than detrimental for the adaptation and survival of species during times of rapid climate change. This project aims to investigate the extent of gene flow among and its effect upon the survival, adaptation and evolutionary history of temporarily isolated populations of animal species during periods of rapid climate change. This goal will be achieved by looking back into the late Pleistocene, when our world experienced repeated and rapid periods of massive climatic change to which species had to adapt. The project will target the evolutionary history of four species (mammoth, spotted hyena, cave bear, and grey wolf) by sequencing large parts of the nuclear genome of each species across both time and space. In each species conflicting evolutionary histories are provided by morphological and mitochondrial DNA analyses, suggesting that (so far undetected) gene flow of nuclear DNA must have occurred. Undetected gene flow may explain aspects of their evolutionary history, and also the way these species adapted to the rapidly changing environmental conditions of the late Pleistocene.

Keywords: ancient dna
The influence of environmental factors on antimicrobial activity of human intestinal defensins (DEFENSINACTIVITY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Germany,Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2018-01-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

Human epithelia are permanently challenged by microorganisms. In the gut, the fraction of strict anaerobic bacteria increases from proximal to distal, reaching 99% of bacterial species in the colon. Moreover, microbial metabolism causes a reduction of the environment to a low redox potential of only –200 mV to –300 mV. Defensins, characterised by three intramolecular disulfide-bridges, are key effector molecules of innate immunity that protect the host from infectious microbes. Human β-defensin 1 (hBD-1) is one of the most prominent peptides of its class but comparison with other defensins suggested only minor antibiotic killing activity. We could recently show that hBD-1 becomes a potent antimicrobial peptide against C. albicans and anaerobic, Gram-positive commensals of the human normal flora in a reducing environment (Nature 2011). The effect was attributable to the linear, reduced hBD-1 peptide. Here we aim to investigate the antimicrobial activity of reduced hBD-1 in more detail. We will study the mechanism of its reduction by cell-culture experiments and in vitro reduction assays. The molecular details of its antibiotic action will be investigated by using bacterial mutants and further in vitro assays. Additionally we aim to characterise the antibiotic spectrum of reduced hBD-1 by using different antimicrobial assays. Also, we plan to systematically test human defensins under reducing conditions and different pH values that occur in the gut Besides we will screen extracts of human intestinal tissue and stool samples for antimicrobial substances by using the conditions described above. Extracts will be purified by HPLC and antimicrobially active fractions will be examined by MALDI-TOF peptide mass fingerprint technique. We hope to identify novel peptides which have been overlooked due to standardized testing methods. Resembling the natural conditions as close as possible will help to better understand antibiotic mucosal host defense in the intestinal tract.

Keywords: antimicrobial peptides,defensins,antimicrobial activity,commensal bacteria,anaerobic bacteria,mucosal barrier,reduction
Drosophila as a model host to study infections by kinetoplastid parasites (DROSO-PARASITE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: United Kingdom
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-03-01
End date: 2018-02-28
Duration (months): 60.0
Total project cost (EUR): 1110126.0
EU funding (EUR): 1110126.0
Participants: 1
Project status: CLOSED

For the vast majority of vector borne parasites the ability to overcome the insect midgut defences is central to transmission. However, for many such diseases we know virtually nothing about the molecular mechanisms involved. For vectors such as tsetse flies and sand flies the prospects for rapidly improving our understanding of key interactions occurring in the midgut when challenged by parasites is bleak. This is because the ‘tool box’ required untangling the interactions is very unlikely to be rapidly developed. For example, there is no realistic prospect of producing transgenic technology for tsetse flies because eggs are inaccessible due to intrauterine development of larvae; maintenance of multiple lines of either sand or tsetse flies permitting genetic studies is impossible because of the cost and complexity of culturing colonies; bioinformatic resources are still in their infancy. In this application we suggest that under these circumstances a comparative approach, in which kinetoplastid interactions in Drosophila melanogaster are studied in the first instance, will permit us to make significant progress in understanding the more important cases of insect-parasite interactions (Trypanosome brucei spp in tsetse and Leishmania in sandflies). Herpetomonas ampelophilae is a natural kinetoplastid parasite of Drosophila melanogaster, which establishes infection in the midgut of the fruit fly and can go on to invade the salivary glands. We now have this protozoan in culture and intend, through a combination of genomics, cell biology and RNAi experiments to identify the gut-specific host genomic contingent involved in parasite challenge. In addition, we will study the interaction between the indigenous flora and the parasite and the role of the former in protecting the host from parasite infection. These studies will outline the major immune pathways and interactions by which insects and their gut microflora respond to kinetoplastid challenge in the midgut.

Keywords: host-pathogen interaction
Cracking the SUMO Signalling Code (DECODINGSUMO)

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: Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1517698.8
EU funding (EUR): 1517698.8
Participants: 1
Project status: CLOSED

Functional activity of proteins is tightly controlled via reversible post-translational modifications including phosphorylation, acetylation and ubiquitylation. These modifications enable the orchestration of cellular responses to a wide variety of stimuli. Due to these modifications, proteomes are overwhelmingly complex. Progress in the field has been greatly accelerated by the development of novel approaches to study these post-translational modifications at a proteome-wide scale using the sensitivity and robustness of mass spectrometry (MS). This has enabled the identification of thousands of dynamically regulated phosphorylation, acetylation and ubiquitylation sites by MS. The functional significance of these modifications is now being addressed worldwide at an unprecedented scale. In contrast, global understanding of ubiquitin-like signalling networks in a site-specific manner is very challenging. Over the last few years, my lab has established novel methodology for the purification and identification of endogenous SUMO target proteins and SUMOylation sites of endogenous targets. The first aim of this project is to uncover small ubiquitin-like modifier (SUMO) signalling pathways in a site-specific manner at a proteome-wide level. The second aim of this project is to reveal how SUMOylation cooperates with ubiquitylation to maintain genome integrity. SUMOylation plays a critical role during the DNA damage response, an important barrier against genome instability linked diseases including cancer and neurodegeneration. Selected target proteins will be studied at the functional and mechanistic level to obtain novel insight in cellular processes that protect against genome instability. The developed methodology is generic and can be applied to study all ubiquitin-like proteins at a proteome-wide level in a site-specific manner, enabling global understanding of ubiquitin-like signalling networks in health and disease.

Keywords: sumo,sumoylation,ubiquitin,ubiquitylation
Ancient Pathogen Genomics of Re-Emerging Infectious Disease (APGREID)

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: Germany,Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1474560.0
EU funding (EUR): 1474560.0
Participants: 2
Project status: CLOSED

Here we propose a first step toward a direct reconstruction of the evolutionary history of human infectious disease agents by obtaining genome wide data of historic pathogens. Through an extensive screening of skeletal collections from well-characterized catastrophe, or emergency, mass burials we plan to detect and sequence pathogen DNA from various historic pandemics spanning at least 2,500 years using a general purpose molecular capture method that will screen for hundreds of pathogens in a single assay. Subsequent experiments will attempt to reconstruct full genomes from all pathogenic species identified. The molecular fossil record of human pathogens will provide insights into host adaptation and evolutionary rates of infectious disease. In addition, human genomic regions relating to disease susceptibility and immunity will be characterized in the skeletal material in order to observe the direct effect that pathogens have made on the genetic makeup of human populations over time. The results of this project will allow a multidisciplinary interpretation of historical pandemics that have influenced the course of human history. It will provide priceless information for the field of history, evolutionary biology, anthropology as well as medicine and will have direct consequences on how we manage emerging and re-emerging infectious disease in the future.

Keywords: ancient dna,ancient pathogen genomics,evolutionary biology,infectious disease
Physiology of the Intestine: Proteases from the Epithelium (PIPE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-04-01
End date: 2018-03-31
Duration (months): 60.0
Total project cost (EUR): 1287000.0
EU funding (EUR): 1287000.0
Participants: 1
Project status: CLOSED

In several gastrointestinal diseases such as irritable bowel syndrome or inflammatory bowel diseases, proteolytic homeostasis is disrupted. This disruption has an important impact of the pathophysiology of those diseases. We hypothesized that intestinal epithelial cells are major regulators of this homeostasis by secreting proteases and protease inhibitors, thereby interfering with gut biological functions and enteric neuron biology. We have generated preliminary data demonstrating that stimulated intestinal epithelial cells release proteolytic activity predominantly on the basolateral side, suggesting that epithelium-derived proteases could then modify mucosal physiology and participate to the dialogue between epithelium and other mucosal cells such as enteric neurons. The aim of the project is to: 1/ characterize the protease/anti-protease balance issued from intestinal epithelium, 2/ study the impact of intestinal epithelium-derived proteolytic machinery on epithelial physiological functions 3/ study the impact of intestinal epithelium-derived proteolytic factors on enteric nervous system activation We believe that results raised from this study will identify previously unknown actors of intestine physiology and pathophysiology and of the neuro-epithelial crosstalks in the gut. Further, we believe that results generated from the present study could have implications more largely on our understanding of mucosal physiology.

Keywords: intestine,gut physiology,neurogastroenterology,epithelium,enteric nervous system,proteases
Finding New Mechanisms for Protein Localization in Bacteria (PROTEINLOCALIZATION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Portugal
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-03-01
End date: 2018-02-28
Duration (months): 60.0
Total project cost (EUR): 1656960.0
EU funding (EUR): 1656960.0
Participants: 2
Project status: CLOSED

During infection, the host immune system interacts with the bacterial cell surface, a complex structure made of peptidoglycan, wall teichoic acids, lipoteichoic acids, capsule polysaccharide and peptidoglycan-attached proteins. A lot is known about the metabolic pathways for the synthesis of each individual cell surface component. Almost nothing is known about the coordination between the synthesis of the peptidoglycan, the major structural component of the cell surface and the main inflammatory component of gram-positive bacteria, and the synthesis of the other molecules present at the surface. However, this coordination is essential for the construction of a surface capable not only of performing its biological functions in cell protection and morphology, but also of masking its inflammatory components for evasion from host recognition. Using the clinical pathogen Staphylococcus aureus as a model organism, we propose to investigate the temporal and spatial regulation of the enzymes responsible for the synthesis of the cell surface components, as well as their dependence on the underlying divisome. We will (i) use state-of –the art fluorescence microscopy to localize fluorescent derivatives of enzymes required for cell surface synthesis; (ii) use libraries of antibiotics, of antisense RNA expression plasmids, and of transposon mutants to identify the order of assembly and requirements for the localization of cell surface synthesis enzymes; (iii) identify the exact metabolic compound/protein/geometric cue responsible for the localization of key enzymes; (iv) determine if cells with impaired surface synthesis due to protein delocalization are more susceptible to host recognition and therefore less capable of causing infections. This project will result in the identification of new mechanisms of protein localization, a fundamental question in cell biology, and in a better understanding of the assembly of the bacterial cell surface of successful bacterial pathogens

Keywords: protein localization,cell wall,staphylococcus aureus,antibiotic resistance
Comparative genomics / ‘wildlife’ transcriptomics uncovers the mechanisms of halted ageing in mammals (AGELESS)

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: Ireland
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2018-06-30
Duration (months): 66.0
Total project cost (EUR): 1499768.3
EU funding (EUR): 1499768.3
Participants: 1
Project status: CLOSED

Ageing is the gradual and irreversible breakdown of living systems associated with the advancement of time, which leads to an increase in vulnerability and eventual mortality. Despite recent advances in ageing research, the intrinsic complexity of the ageing process has prevented a full understanding of this process, therefore, ageing remains a grand challenge in contemporary biology. In AGELESS, we will tackle this challenge by uncovering the molecular mechanisms of halted ageing in a unique model system, the bats. Bats are the longest-lived mammals relative to their body size, and defy the ‘rate-of-living’ theories as they use twice as much the energy as other species of considerable size, but live far longer. This suggests that bats have some underlying mechanisms that may explain their exceptional longevity. In AGELESS, we will identify the molecular mechanisms that enable mammals to achieve extraordinary longevity, using state-of-the-art comparative genomic methodologies focused on bats. We will identify, using population transcriptomics and telomere/mtDNA genomics, the molecular changes that occur in an ageing wild population of bats to uncover how bats ‘age’ so slowly compared with other mammals. In silico whole genome analyses, field based ageing transcriptomic data, mtDNA and telomeric studies will be integrated and analysed using a networks approach, to ascertain how these systems interact to halt ageing. For the first time, we will be able to utilize the diversity seen within nature to identify key molecular targets and regions that regulate and control ageing in mammals. AGELESS will provide a deeper understanding of the causal mechanisms of ageing, potentially uncovering the crucial molecular pathways that can be modified to halt, alleviate and perhaps even reverse this process in man.

Keywords: molecular zoology,wildlife transcriptomics,bat biology,mammalian diversity,ageing model,phylogenomics
The Origin of Jawed Vertebrates and the Evolution of Morphology in Deep Time (JAWEVOL)

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: United Kingdom,Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2018-12-31
Duration (months): 72.0
Total project cost (EUR): 1401820.0
EU funding (EUR): 1401820.0
Participants: 2
Project status: CLOSED

Jawed vertebrates account for more than 99% of modern vertebrate diversity. Collectively, they comprise chondrichthyans (sharks, rays, and chimaeras) and osteichthyans (bony fishes and terrestrial vertebrates, including humans). The anatomy of jawed vertebrates includes a series of complex traits such as jaws, teeth, paired appendages, and novel skeletal tissues such as bone. In spite of the intensive investigation of jawed vertebrate evolution in comparative morphology and molecular developmental evolution, the origin and early diversification of this important group remains mysterious. This project seeks to inject a large body of fresh data into the problem of early jawed vertebrate origins and evolution and develop modernized tools for morphological phylogenetics. We will use an integration of expeditionary fieldwork, modern digital imaging technology, and newly developed numerical methods in phylogenetics to address the problems of early jawed vertebrate origins. The work will focus on the morphology and relationships of fossil jawed vertebrates from the Palaeozoic Era (approx. 540-250 million years ago) which exhibit the earliest evidence of jaws, teeth, and paired appendages. Fieldwork in Mongolia will deliver new taxonomic and morphological data from poorly explored regions and attack a major geographic bias in existing fossil archives. The project will exploit computed tomography scanning to analyze existing fossil archives of extract species. This work will provide a detailed scheme of phylogenetic relationships inferring the relationships of early fossil forms to modern jawed vertebrate lineages and document the evolutionary assembly of complex morphological traits of jawed vertebrates. These results will yield refined timelines for jawed vertebrate evolution that can help calibrate molecular clock studies and deliver a rich comparative framework for evolutionary morphological and developmental studies.

Keywords: morphology,palaeozoic,vertebrates