Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
DNA damage response and genome stability: The role of ATM, ATR and the Mre11 complex (AAMDDR)

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-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-06-30
Duration (months): 60.0
Total project cost (EUR): 1000000.0
EU funding (EUR): 1000000.0
Participants: 1
Project status: CLOSED

Chromosomal DNA is continuously subjected to exogenous and endogenous damaging insults. In the presence of DNA damage cells activate a multi-faceted checkpoint response that delays cell cycle progression and promotes DNA repair. Failures in this response lead to genomic instability, the main feature of cancer cells. Several cancer-prone human syndromes including the Ataxia teleangiectasia (A-T), the A-T Like Disorder (ATLD) and the Seckel Syndrome reflect defects in the specific genes of the DNA damage response such as ATM, MRE11 and ATR. DNA damage response pathways are poorly understood at biochemical level in vertebrate organisms. We have established a cell-free system based on Xenopus laevis egg extract to study molecular events underlying DNA damage response. This is the first in vitro system that recapitulates different aspects of the DNA damage response in vertebrates. Using this system we propose to study the biochemistry of the ATM, ATR and the Mre11 complex dependent DNA damage response. In particular we will: 1) Dissect the signal transduction pathway that senses DNA damage and promotes cell cycle arrest and DNA damage repair; 2) Analyze at molecular level the role of ATM, ATR, Mre11 in chromosomal DNA replication and mitosis during normal and stressful conditions; 3) Identify substrates of the ATM and ATR dependent DNA damage response using an innovative screening procedure.

Keywords: dna damage checkpoint,atm,atr,mre11,xenopus laevis
Modelling cancer in Caenorhabditis elegans (CANCEROMICS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2007-10-01
End date: 2012-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

Cancer is a complex disease that results from accumulation of diverse alterations in the genome. There are more than 300 genes identified as “cancer genes” although it is estimated that there are many more involved in cancer development that could be significant during tumorigenesis and putative targets for drugs therapies. Several scientific groups are performing a comprehensive sequencing of genes in cancer cells but these studies lack of functional validation. Since cancer requires the combination of several defects in the genome, an organism amenable for genetics and functional genomics studies as Caenorhabditis elegans would provide the ideal platform to identified those fatidic combinations. I plan to take advantage of C. elegans mutants and a “RNA interference” (RNAi) library to uncover functions and pathways of the following C. elegans genes: A) SWI/SNF complex subunit ZK1128.5 baf-60: The SWI/SNF complex is conserved from yeast to humans and acts in chromatin remodelling to regulate gene expression. baf-60 mutants present extra proliferation at particular lineages. B) Claspin, F25H5.5: Human Claspin acts as a DNA damage checkpoint through the activation of chk1 protein kinase. chk-1 also acts as a DNA damage checkpoint in C. elegans. I have preliminary results in C. elegans pointing to a novel role of Claspin in genome stability. C) Spliceosome (or splicing-related) components rsr-2 and lsm-2: I have recently published that rsr-2 and lsm-2 act in the RAS pathway that determine the vulval cell fate in C. elegans (Ceron et al, 2007). This observation and others suggests functional relationships between spliceosome-related genes and cancer. The discovery of functional networks for these genes will contribute to create a “Functional map for cancer genes” that will be a essential toward understanding this complex disease and, ultimately, find effective therapies.

Keywords: genomics,functional biology
Unraveling the molecular mechanisms leading to cellular dysfunction in diseases linked to defects in mitochondrial iron-sulfur cluster metabolism (ISCATAXIA)

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-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-06-30
Duration (months): 60.0
Total project cost (EUR): 1449924.0
EU funding (EUR): 1449924.0
Participants: 1
Project status: CLOSED

The project aims at unraveling the molecular pathophysiology of recessive ataxias, a heterogeneous set of severely disabling neurodegenerative disorders due to loss of function of proteins involved either in mitochondrial/metabolic pathways or DNA repair. Friedreich ataxia, the most common form, is due to partial loss of function of frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Furthermore, the rare X-linked sideroblastic anemia with cerebellar ataxia is caused by mutation in ABCb7, an ATP-binding cassette transporter of the mitochondrial inner membrane necessary for cytosolic ISC export. ISC are versatile co-factors of proteins involved in electron transport, enzyme catalysis and regulation of gene expression. The synthesis and insertion of ISC into apoproteins involve complex machineries that are still poorly understood in the mammalian cell. The objectives of this proposal are: 1) to elucidate ISC biogenesis and metabolism in the mammalian cell, with an emphasis on the role of frataxin and ABCb7; 2) to better understand the molecular pathways that are involved in neuronal dysfunction due to defects in mitochondrial ISC metabolism. These objectives will be accomplished by a multidisciplinary approach combining molecular and biochemical approaches to study the ISC assembly machineries, bioinformatic and proteomic studies to identify new Fe-S proteins, the development and pathological analysis of animal and cellular models to dissect the molecular mechanisms, and transcriptomic analysis to uncover the common pathways among recessive ataxias. A specific focus of the proposal will be the involvement of DNA damage response pathways in neuronal dysfunction, as several DNA repair enzymes have recently been identified as Fe-S proteins and thus might be directly affected by frataxin and ABCb7 deficiency. This proposal should lead to the identification of different pathways for therapeutic intervention for these devastating disorders.

Keywords: mitochondria,recessive ataxia,animal and cellular models,fe-s and iron metabolism
Role of the proto-oncogene Ret during lymphocyte development and function (RETIMMUNEFUNCTION)

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: Portugal
Call:  (ERC-2007-StG, 2007)
Start date: 2008-11-01
End date: 2013-10-31
Duration (months): 60.0
Total project cost (EUR): 1901400.0
EU funding (EUR): 1901400.0
Participants: 1
Project status: CLOSED

There is growing evidence that molecules classically allocated to nervous system function, such as the neurotrophic factors, are produced by lymphocytes and can also regulate their function. The neurotrophic family includes the GDNF ligands (GFLs), which signal through the RET tyrosine kinase receptor. In humans, mutations of the proto-oncogene Ret have been linked to different diseases, such as cancer and Hirschsprung’s disease. Interestingly, RET expression has been reported in lymphocytes but its functional significance is unclear. We propose to use combined genetic, cellular, and molecular approaches in order to determine, quantify and manipulate the function of RET and GFLs during haematopoiesis and lymphocyte differentiation. In order to achieve this, we will analyse the patterns of RET and GFL expression during haematopoiesis, and in mature lymphocyte sub-sets. By using this strategy we aim to identify differentiation stages where the Ret exerts its role. We then plan to assess the functions of RET and candidate GFLs by studying the impact of Ret and GFL gene ablation. To achieve this, we will study lymphoid cells at different stages of differentiation from mice deficient for Ret or GFLs, and determine the role that these molecules play in key cellular and molecular events during haematopoiesis and immune responses. Since RET is likely to exert its function at various differentiation steps, we plan to use genetically modified mice allowing the conditional deletion of Ret. As a complementary approach, we will generate mice over-expressing RET or constitutively activated RET in a tissue-specific manner, thus mimicking activating mutations of RET associated with cancer. We believe our work, apart from its novelty in the field of immunology, will have a broader impact in other disciplines. Indeed, mechanisms historically ascribed to a specific tissue may be used more generally in order to orchestrate the function and communication among different systems.

Keywords: lymphocyte differentiation neurotrophic factors proto-oncogenes genetically modified mice
Economic analysis of certification systems for organic food and farming (CERTCOST)

Framework: FP7 — Cooperation
Programme: Food, Agriculture and Fisheries, and Biotechnology
Destination: Sustainable production and management of biological resources from land, forest, and aquatic environment
Action type: Collaborative project
Countries involved: Germany,Switzerland,Italy,Germany,Türkiye,Denmark,Czechia,United Kingdom,United Kingdom
Call:  (FP7-KBBE-2007-1, 2007)
Start date: 2008-09-01
End date: 2011-11-30
Duration (months): 39.0
Total project cost (EUR): 3481895.35
EU funding (EUR): 2733185.0
Participants: 11
Project status: CLOSED

With the ongoing growth of the organic sector and the spread of organic production across the EU, the field of organic certification has become a maze of competing labels and logos, involving different private and public standards, in addition to European law. This diversity reflects the specific conditions for organic operators in countries or regions but can also lead to confusion for both producers and consumers and may create a variety of costs. Reg. (EC) 834/2007 intends a review of the revised regulation by the year 2011. It is imperative to conduct a comprehensive economic analysis of the variety of existing certification systems and their impact on the internal market for organic goods. This project proposes to combine the experience and knowledge of both researchers and SMEs to fulfil the following objectives: analyse the implementation of organic certification systems and estimate all relevant expenditures or transaction costs for different certification systems along the organic food supply chain in various regions of the EU, including a candidate country and Switzerland. It will involve stakeholders. Access to the necessary data has already been agreed with the involved partners or appropriate agencies for all seven study countries. In addition to costs, benefits of certification will be analysed, using data on consumers&apos; recognition, image and willingness to pay for different organic logos and trademarks, with their underlying production standards and certification procedures. The project will consider consumer and certification issues equally. Economic models will be applied to analyse the determinants of costs and benefits, as well as provide recommendations for the development of risk-based certification systems. Finally, recommendations will be drawn for the EU Commission, national competent authorities and private actors in organic food and farming on how to increase effectiveness and efficiency of organic certification.

Keywords: certification,standard setting,transaction costs,economics,concumer perception of organic logos,economic modelling,stakeholder integration
IDENTIFICATION OF THE GENES REGULATED BY THE SIRT1 HISTONE DEACETYLASE AND THEIR CONTRIBUTION IN THE PATHOGENESIS OF TYPE 2 DIABETES AND OBESITY (SIRT1 AND DIABETES)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-02-01
End date: 2012-01-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Type 2 diabetes is the most common metabolic disease and is characterized by insulin resistance in the liver, adipose tissue and skeletal muscle and impaired insulin secretion. Type 2 diabetes is a polygenic disorder which also involves environmental factors and is tightly correlated with obesity. Therefore, the identification of the genes associated with increased susceptibility to these diseases is difficult. At present, therapies for this disease are not completely effective and present secondary effects. To design new therapies, a better knowledge of molecular regulation of the expression of genes implicated in the pathology of diabetes is necessary. Gene regulation at transcriptional level has been demonstrated to be directly correlated, among other factors, with chromatin structure which may be altered by covalent modifications of NH2-terminal end of histones, mainly through acetylation. The balance between acetyl transferase (HAT) and deacetylase (HDAC) activities controls the histone acetylation status. Among HDAC enzymes, sirtuin 1 (SIRT1) has been shown to suppress glycolytic pathway and to induce gluconeogenesis in the liver, two of the main alterations in the diabetic process. Thus, modifications in the histone acetylation level may be involved in the onset and the development of diabetes. Therefore, the main objective of this project is the identification of target genes for SIRT1 by using ChIP-chip methodology (hybridization of specific promoter microarrays (chip) with the products of chromatin immunoprecipitation (ChIP). The contribution of these genes to the diabetic process will be further evaluated by the generation and the study of genetically engineered animals by gene transfer. The results of this study may contribute to a better understanding of the mechanisms of gene transcription regulation, which may lead to potential development of new therapies for type 2 diabetes and obesity.

Keywords: natural sciences,health sciences,chromatin immunoprecipitation,dna microarrays,gene therapy,histone modifications
Femtosecond Raman Spectroscopy: ultrafast transformations in physics, chemistry and biology (FEMTOSCOPY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Condensed matter physics
Countries involved: Italy
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2013-08-31
Duration (months): 60.0
Total project cost (EUR): 1544400.0
EU funding (EUR): 1544400.0
Participants: 1
Project status: CLOSED

We propose the construction and development of a femtosecond broadband stimulated Raman setup to tackle ultra fast chemical, physical and biological processes taking advantage of the top-notch structural sensitivity inherent to the Raman process. The use of a pump-probe stimulated scheme will allow to overcome time-energy restrictions dictated by the uncertainty principle, enabling to reach the femtosecond timescale with energy resolutions which would pertain to the picosecond time domain in the Heisenberg sense. Protein dynamics span several orders of magnitude extending up to macroscopic timescales, the recipes to tailor properties of rubbers and polymers relevant for human timescales are covered by more than 500000 patents, rust reaction occurs over several days, and lethal brain strokes often lead to death within 24 hours on average. The lowest hierarchical level of such processes, however, is hidden in the very act of atomic motion and chemical binding such as the single bond dynamics in a peptide backbone, the monomer cross-linking elemental reactions, the energy flow and re-distribution in a hydrogen bond network, or the oxygen binding to heme proteins, all performing on the femtosecond stage. Mastering these processes is the essence of femtochemistry, born around the backbone of the femtosecond laser technology and boosted by scientific activity which led to the Nobel prize of Prof. A. Zewail in 1999. The new capabilities offered by femtosecond sources have often left behind in the race traditional spectroscopies, which hardly follow the growing emergence of new challenging problems in which the traditional distinction between biology, chemistry and physics is smeared out by the common ultra short timescale. The set up of a non conventional femtosecond Raman technique will be the initiating event for the establishment of a research group of interdisciplinary nature toiling over unsolved problems in which the ultrafast facet plays a key role.

Keywords: raman,ultrafast transformations,femtosecond
Statistical and Computational Genetics Tools for Investigation of Human History from Large Genetic Datasets (SAHARONIRG)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2007-10-01
End date: 2011-09-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

This proposal concerns the development of new statistical and computations methods for drawing inferences from genetic data. As a member of the Genographic Consortium, the author has access to both vast amounts of genetic data, and an array of scientific collaborators worldwide, seeking to answer questions regarding history of the human species, ancient migrations, etc. through analysis of genetic data. Some of the work already performed includes a method for mutation probability estimation from large datasets, and a paper on analysis of a large mtDNA database. A number of exciting challenges for the future work are discussed. Once the author joins the faculty at Tel Aviv University, this research will contribute to ongoing international collaboration, to inter-disciplinary collaboration within the University and to increasing our understanding about the past --- and future --- of our species, and the manner in which people world wide are connected to each other as members of one extended family.

Keywords: molecular genetics,population genetics,statistics,human history,evolutionary genetics
Spin currents in magnetic nanostructures (MASPIC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Condensed matter physics
Countries involved: Germany,Germany
Call:  (ERC-2007-StG, 2007)
Start date: 2008-08-01
End date: 2014-04-30
Duration (months): 69.0
Total project cost (EUR): 1610786.0
EU funding (EUR): 1610786.0
Participants: 2
Project status: CLOSED

MaSpic will create an autonomous team at the University of Konstanz to investigate the interaction between magnetization, spin - polarized and pure diffusive spin currents using novel instrumentation and innovative theoretical approaches. A thorough understanding of the fundamental charge and spin transport interaction mechanisms, key to use of the spin degree of freedom for Spintronics, will be developed. To understand the interplay between spin-polarized charge currents and magnetization configurations (adiabatic vs. non-adiabatic electron transport), the reciprocal effects of magnetization on the current (magnetoresistance) and of the current on magnetization (spin transfer torque) will be correlated for the same spin structures. Non-intrusive high resolution imaging at variable temperature will be used to probe the non-adiabaticity and help understand the hotly debated influence of thermal excitations on transport. Pure diffusive spin currents will be efficiently generated and used to manipulate magnetization with ultra-low power dissipation. The poorly understood spin current generation by the Spin Hall Effect and spin current propagation will be probed by direct imaging and the sign of the spin accumulation and influence of scattering determined to separate intrinsic and extrinsic effects. For the measurements a unique variable temperature high resolution SEMPA imaging system will be acquired and further developed including ultra-fast electrical contacts. Theoretical modelling using an atomistic Heisenberg approach will go beyond the conventional micromagnetic calculations that are limited to 0K. To understand thermal transport effects, temperature dependent simulations with adiabatic and non-adiabatic spin torque terms will accompany experiments. Realistic lattice structures and heterostructures will be modelled to simulate the influence of the pure spin currents on the magnetization using spatially varying interface torque terms, not previously possible.

Keywords: spin torque,spin currents
Improving subgrid-scale cloud parameterization in global climate models using remote sensing data (SUBGRID-SCALE CLOUDS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2007-09-01
End date: 2011-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Climate change is probably the most important challenge facing mankind. Our understanding of the climate system and ability to make projections about its future evolution are based almost exclusively on global climate models. Although climate models have shown remarkable improvement in recent years, their projections are still subject to large uncertainties. It is well established that clouds are the weakest link in climate simulations. The poor representation of the many cloud-related processes such as precipitation, aerosol indirect effects, and cloud-radiation interactions is the major source of uncertainty in climate models. Fortunately, a treasure trove of measurements from a new generation of earth observing satellites has become available in recent years. The aim of this proposal is to significantly improve the representation of clouds in the global climate model of the Max Planck Institute for Meteorology by tapping into this large remote sensing data set. In particular, we propose to develop a statistical approach based on probability density functions to better describe subgrid-scale cloud processes such as horizontal and vertical cloud variability, and convection. It is expected that this effort will have resulted in substantially improved climate change projections by the time of the Fifth Assessment Report of the Intergovernmental Panel on Climate Change, currently scheduled to be prepared in the 2010-2013 period.

Keywords: natural sciences,climate modeling,cloud physics,radiation,atmospheric remote sensing,cloud-climate feedback