Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
SIRT6 activation for countering age-related metabolic diseases (SIRAID)

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: Israel
Call:  (ERC-2009-StG, 2009)
Start date: 2009-10-01
End date: 2014-09-30
Duration (months): 60.0
Total project cost (EUR): 1510968.0
EU funding (EUR): 1510968.0
Participants: 1
Project status: CLOSED

The significant increase in the human lifespan during the last century confronts us with great medical challenges. To answer them, one must understand and control the mechanisms that determine the rate of ageing. The sirtuins, and in particular the mammalian member SIRT6, are a family of NAD+ dependent deacetylases that were implicated in ageing and the regulation of metabolism. Much evidence correlates SIRT6 with the regulation of ageing, primarily the manifestation of ageing related pathologies in SIRT6 deficient mice, and the induction of SIRT6 by calorie-restricted diet that delays ageing and reduces its related diseases. Nonetheless, the role of SIRT6 in ageing and the mechanisms by which it might act are still elusive. To explore it at the molecular mechanistic level, SIRAID aims to i) study the role of SIRT6 in glucose and fat metabolism under high fat diet; ii) to determine whether SIRT6 is involved in regulating life span, and to characterise how SIRT6 is activated by calorie restriction; and iii) to perform large scale SILAC-based proteomics screening for SIRT6 substrates. These results will then be used for the development of small activator molecules of SIRT6 that may be used therapeutically for age related metabolic diseases. Taken together, we suggest a multifaceted approach that will allow us to explore the role of SIRT6 in ageing and metabolism, and to translate this knowledge to counter and prevent the medical problems associated with human longevity.

Keywords: sirtuins,sirt6,ageing,metabolic syndrome obisity,obesity
Rewiring cortical areas through thalamocortical inputs (RECORTHA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Spain
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2015-06-30
Duration (months): 66.0
Total project cost (EUR): 1478400.0
EU funding (EUR): 1478400.0
Participants: 1
Project status: CLOSED

Research into neuroplasticity has expanded rapidly over the past ten years and it has revealed the remarkable capacity of environmental inputs to shape both the juvenile and adult brain. Behavioural, electrophysiological and neuroimaging studies in deaf and blind humans have provided convincing evidence that alteration of cortical organization is correlated with enhanced capabilities of the spared modalities. What is the identity of the brain systems that are modified and what are the mechanisms that mediate such changes are major unresolved issues in our understanding of brain plasticity. RECORTHA aims to address this challenge and identify the mechanisms underlying the rewiring of brain connections with a particular focus on the thalamocortical system. We will adopt innovative multidisciplinary approaches (from gene to behaviour) to understand how thalamocortical wiring influences, maintains and ultimately shape the functional architecture of the cortex. Taking advantage of mouse genetics, we will generate new models of cross modal plasticity in which we can directly test the capacity of thalamocortical inputs to restore sensory information. Furthermore, we will determine to what extent this rewiring is triggered by activity dependent mechanisms in the thalamus. These findings will contribute to our understating of how reprogramming of cortical wiring takes place following brain damage that will be essential for efficient functional restoration in sensory disabilities.

Keywords: thalamus,electrical activity,axon guidance,wiring,behaviour
Biomolecular Motor Systems: From Cellular Function to Nanotechnological Applications (NANOTRANS)

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: Germany,Germany
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2015-10-31
Duration (months): 72.0
Total project cost (EUR): 1956000.0
EU funding (EUR): 1956000.0
Participants: 2
Project status: CLOSED

This interdisciplinary project aims (i) to understand intracellular transport processes on a molecular level using novel nano-optical imaging tools and (ii) to use the insight from cellular systems to operate biomolecular motor systems in engineered environments for the fulfillment of complex nanotechnological tasks. Building on experience in optical microscopy and single molecule biophysics the research group will develop and apply nanotechnology-based tools to study the dynamical functioning of microtubule-based motor proteins in vitro and in vivo with nanometer resolution in three dimensions. These studies are expected to broaden the general knowledge about the design principles of molecular machines as well as the principles by which they interact with each other. This knowledge will - in return - pave the road for applications of these highly evolved transport machineries for a wide range of self-organizing nanofunctions in engineered environments. In contrast to conventional &quot;macroscopic&quot; top-down or &quot;atomic&quot; bottom-up approaches, a driving factor for this research is the capability of cellular machines to work in parallel, thus enabling the efficient fabrication and detection of nanostructures. The project will be strongly focussing on the interface between molecular cell biology and nanotechnology. With respect to the applied ERC funding, the project goals can be described by: Goal 1: Single-molecule studies on motor proteins using optical 3D-nanometer imaging, Goal 2: Investigation of cooperative effects in multi-motor transport, Goal 3: External control over transport systems in engineered environments, and Goal 4: Application of motor systems for nano-manipulation and nano-detection. Regarding the long-term goal, it is envisioned to let smart nanomaterials fulfill biological functions in cellular systems and to efficiently operate biomolecular machines in engineered environments.

Keywords: biomolecular motors,cytoskeleton,single-molecule imaging,optical nanometry
The role of heterochromatin enzymes on the biology of their targets (PICHV2.0)

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: France
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2014-12-31
Duration (months): 60.0
Total project cost (EUR): 1707500.0
EU funding (EUR): 1707500.0
Participants: 1
Project status: CLOSED

The control of DNA based processes in biology is crucial for an organism s life, development, reproduction and evolution. In fact, deregulation of gene expression, of the replication program, of DNA repair or recombination has often disastrous consequences. The eukaryotic genome is structurally and functionally organized into chromatin by a highly complex mixture of proteins that control access to the DNA. In particular, heterochromatin proteins play a prominent role in this control. Genetics, biochemistry and molecular biology identified many players involved in eukaryotic DNA biology and provided everything we currently know about it. However the full composition of a given locus remains largely obscure and just like any object under scientific study, knowing the composition is an absolute pre-requisite for a full understanding of its features. Consequently, the nature of the interactions between chromatin structural components and DNA machineries is poorly understood and the elaboration of models from rather incompletely characterized systems can be misleading. During my post-doctorate, I have developed an unbiased approach for the in vivo purification of chromatin proteins in a locus specific manner, and I intend to apply this new technology in combination with a genetic approach. Monitoring the consequence of heterochromatin protein loss on the full composition of regulated loci will allow a deeper understanding of the role these proteins in the regulation of eukaryotic genome biology.

Keywords: telomere,satellite,heterochromatin,dna methylation,non coding rna
Tropical forests and climate change: understanding links to predict future responses (TROFOCLIM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: ERC Starting Grant Interdisciplinary Panel
Countries involved: Netherlands,Netherlands
Call:  (ERC-2009-StG, 2009)
Start date: 2010-02-01
End date: 2015-01-31
Duration (months): 60.0
Total project cost (EUR): 1729200.0
EU funding (EUR): 1729200.0
Participants: 2
Project status: CLOSED

Tropical forests cover just 7% of the Earth s surface, but store 25% of the global terrestrial carbon pool. Since they are so rich in carbon, net loss or uptake of carbon by tropical forests has important implications for atmospheric CO2 levels. Thus, tropical forests can speed up climate change by net emission of CO2 or slow it down by net sequestration. The rise in atmospheric CO2 level since the onset of the Industrial Revolution and the resulting climatic changes have certainly affected tropical forest dynamics. Understanding the impacts of these changes so far is crucial to predict future responses. Recent studies have shown that tropical forests have acted as carbon sinks over the last decades. However, it is unclear whether these forests have accumulated biomass already over the longer periods of time during which CO2 levels have risen and climate has changed. It is also unknown what has caused the observed biomass increase. The proposed study has the objective to detect, explain and predict long-term climate change effects on tropical tree dynamics. To this end, I will apply three techniques which are new to this field: tree ring analysis, stable isotope measurements and tree growth modelling. This is the first pan-tropical study that analyses centennial-scale tree growth. The study will be conducted at three sites (Bolivia, Cameroon, Thailand) and includes 15 tree species. I will test for gradual changes in long-term tree growth using tree ring data. Stable isotopes (C, O) will be measured to reconstruct past climate and detect responses to CO2 rise. The influence of changes in forest dynamics on tree growth will also be assessed. Finally, I will develop and apply physiological tree growth models and population models to unravel the complex interactive effects of climatic changes, CO2 rise and light climate on tree growth and population dynamics.

Keywords: climate change,tropical forests,tree ring analysis,stable isotope analysis,tree demography
Regulation and Function of Cullin-Ring E3 ubiquitin ligases and the Nedd8 ubiquitin-like protein modification system (NEDD8ANDCRLLIGASES)

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: United Kingdom
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2014-10-31
Duration (months): 60.0
Total project cost (EUR): 1397676.6
EU funding (EUR): 1397676.6
Participants: 1
Project status: CLOSED

Cullin-RING E3 ubiquitin ligases (CRLs) are multi-subunit enzyme complexes that catalyze isopeptide bond formation between the C-terminal glycine residue of the small protein ubiquitin and lysine residues of substrate proteins (ubiquitination). Multiple rounds of ubiquitination lead to the formation of ubiquitin chains, which are recognized by the 26S-proteasome, a protease that degrades the substrates. Targeted protein degradation by CRLs is an important part of many essential cellular processes. Progression of the cell cycle, for example, requires CRL-dependent ubiquitination and degradation of cyclin-dependent kinase inhibitors (CKIs). Clearly, substrate ubiquitination needs to occur at the right time and place, and it is thus essential that CRL activity is tightly regulated. In fact, the malfunction of CRLs has been associated with many human diseases, including cancer. One mode of CRL regulation is the activation of the ligase by the small ubiquitin-like molecule Nedd8 (neddylation). Neddylation of the cullin triggers the formation of an active ligase complex and induces structural changes that allow efficient substrate ubiquitination. My proposal aims at gaining mechanistic insights into the activation and inactivation cycles of CRL complexes. I propose to study the regulation of cullin neddylation and the role of the newly identified Nedd8 E3 ligase Dcn1 in this process. I will identify new substrates of the Nedd8 pathway with yeast genetics and biochemistry and generate a systems-wide map of genetic interactions with CRL substrates and regulators using synthetic genetic array (SGA) analysis.

Keywords: ubiquitin,nedd8,cullin-ring ubiquitin ligases,budding yeast,s. cerevisiae,synthetic genetic arrays,biochemical reconstitutions
Evolutionary Epidemiology of Infectious Diseases (EVOLEPID)

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: France
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2014-12-31
Duration (months): 60.0
Total project cost (EUR): 1308660.0
EU funding (EUR): 1308660.0
Participants: 1
Project status: CLOSED

Our ability to control infectious diseases relies on a better understanding of epidemiological and evolutionary dynamics of pathogens. I will develop a research program combining theoretical and experimental approaches. First, I will extend the theoretical framework of evolutionary epidemiology into several new directions to study (1) the evolution of host and pathogen key life-history traits (parasite virulence, host resistance and host manipulation by the parasite) and, (2) the dynamics of adaptation of pathogens in constant and variable environments. This part of the project will be grounded on both mathematical epidemiology and population genetics. Second, I will use two biological models to test some of these theoretical predictions both in the laboratory and in the field: (1) I will study the interaction between the avian malaria parasite (Plasmodium relictum) and its mosquito vector (Culex pipiens) to test some of the predictions generated on life-history evolution, and in particular on host manipulation by the parasite. (2) I will study the evolutionary dynamics of the coliphage phix174 under different scenarios of environmental heterogeneity to test the predictions issued from models on the dynamics of adaptation in variable environments. In addition, I will measure patterns of adaptation across space and time using natural samples of viral and bacterial communities. The originality of this project lays in the combination of different perspectives on the dynamics of infectious diseases, ranging from theoretical population genetics to experimental behavioural ecology and evolution. Combining these different perspectives will yield a more comprehensive view of the dynamics of infectious diseases and contribute to the improvement of public-health interventions.

Keywords: infectious disease,epidemiology,adaptation,experimental evolution,bacteriophage,avian malaria
Single-cell Gene Regulation in Differentiation and Pluripotency (SINGLE-CELL GENOMICS)

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: Sweden
Call:  (ERC-2009-StG, 2009)
Start date: 2010-02-01
End date: 2015-01-31
Duration (months): 60.0
Total project cost (EUR): 1654383.6
EU funding (EUR): 1654383.6
Participants: 1
Project status: CLOSED

We aim to study transcriptomes with single-cell resolution, a long-standing goal in biology, to answer fundamental questions about gene regulation. The main objective concerns gene regulation during in vivo differentiation and in pluripotent cells by studying single-cells from murine preimplantation embryos, a model system with natural single-cell resolution, important biology and medical potential. This would also allow us to explore general regulatory principles of gene expression programs of individual cells. This research program will be accomplished by novel deep sequencing technology of mRNAs (mRNA-Seq) to obtain quantitative, unbiased and genome-wide gene and isoform expression measurements. We are therefore developing new experimental and computational methods for genome-wide analyses of transcriptomes at single-cell resolution. The biological significances of the proposed research are unique insights into early embryonic development. Deep sequencing of transcriptomes will also reveal post-transcriptional gene regulation important for pluripotent cells and identified pluripotency-specific gene and isoform expressions will be important for future stem cell based therapies. The inherit single-cell nature of the model system together with its important biology makes it a model systems exceptionally well suited for a systems biology approach aiming to characterize gene regulation at single-cell resolution. The novel methodology has tremendous potential to enable complete mRNA characterization of individual cells. The deep sequencing approach with state-of-the-art computational analyses is both more quantitative than previous methods and it will give readouts on alternative isoforms generated by alternative promoters, splicing and polyadenylation.
Spatio-temporal regulation of antigen presentation and cell migration (STRAPACEMI)

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: France
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2015-11-30
Duration (months): 72.0
Total project cost (EUR): 1980000.0
EU funding (EUR): 1980000.0
Participants: 1
Project status: CLOSED

The immune system is constituted by different cell populations, which circulate between lymphoid organs and peripheral tissues as a result of their high migratory capacity. We have shown that Antigen (Ag) processing and migration of Ag Presenting Cells (APCs) are co-regulated by a protein complex that contains the MHC class II-associated Invariant Chain (Ii) and the actin-based motor protein Myosin II. While the association between Ii and Myosin II promotes Ag processing for presentation onto MHC class II molecules, it impairs APC motility, suggesting that the use of common regulators enables APCs to coordinate Ag processing and cell migration in time and space. We here propose an innovative multi-disciplinary approach, at the interface of immunology, cell biology and biophysics, aimed to unravel the fundamental mechanisms allowing the coordination of Ag processing and APC migration and to evaluate their impact on the adaptive immune response. Our specific aims stand as follows: (1) Combine two-photon microscopy in living tissues and micro-fabricated tools to highlight the molecular mechanisms by which the Ii-Myosin II complex couples Ag processing and cell migration in APCs. (2) Use mouse models to provide a quantitative analysis of the impact of the coordination of Ag processing and APC migration on the onset of the adaptive immune response in vivo. (3) Extend this analysis by performing a genetic screen to identify the molecules and cellular parameters that are critical for coordination of Ag processing and APC migration. The molecular mechanisms that regulate cell motility being conserved between the different types of leukocytes, we foresee that our results will shed light on the fundamental immunological question of how immune cells in general regulate their individual effector function in time and space.

Keywords: antigen presentation,cell motility and migration,cytoskeleton dynamics,membrane trafficking,live-imaging.
Sensory perception: neural representation and modulation (ZEBRAFISH PERCEPTION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: France
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2015-09-30
Duration (months): 71.0
Total project cost (EUR): 1851600.0
EU funding (EUR): 1851600.0
Participants: 1
Project status: CLOSED

Perception has intrigued philosophers and scientists since Aristotle ~2,300 years ago, but only recently it became technically possible to address its underlying neural mechanisms. The main scientific research approach still focuses on studying the evoked responses to a perceived sensory stimulus. However, in a state of sensory deprivation, sensory areas in the brain remain highly active. This activity, once interpreted as irrelevant noise, has been found to exhibit highly coherent spatiotemporal structures, suggesting a possible role in perception. Here, I propose to test the hypothesis that perception results as a consequence of the interaction between the dynamic internal state of the brain and the activity evoked by sensory experience. For this purpose, I shall use the zebrafish larva as the experimental model, and a multidisciplinary approach involving two-photon imaging of neural network activities with single cell resolution, behavioural assays, novel mathematical methods for data analysis and genetic engineering techniques to label and manipulate activity of specific cell types or entire networks. The zebrafish model offers the advantage of combining simultaneously all these techniques in an intact behaving vertebrate. I shall specifically examine: 1) The Neuronal representation of sensory perception 2) The role of ongoing spontaneous activity in sensory perception 3) The effect of sensory experience on perception The proposed multidisciplinary approach will shed new light on how information flows through the nervous system; how sensory stimuli are detected, processed and converted into motor behaviours. The findings of this project should provide clear hypotheses regarding analogous and poorly-understood processes in mammals. The work could therefore contribute to understanding of neurological disorders, such as tinnitus, phantom limb and other hallucinations, in which sensory experience is perceived in the absence of external stimulation.

Keywords: zebrafish,two-photon microscopy,calcium imaging,visual perception,ongoing activity,neural networks,sensory experience,behaviour,perception modulation