Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Sorting out Polarized Transport in Neurons: Motor Protein Selectivity and Cooperativity (POLARIZEDTRANSPORT)

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: Netherlands
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Neurons are the building blocks of the brain. The ability of neurons to receive, process and transmit information depends on their polarized organization into axons and dendrites. To build such a highly polarized cell, cellular components synthesized in the cell body are differentially transported to either axons or dendrites. Polarized transport is driven by three families of cytoskeletal motor proteins, which can walk in different directions over the actin or microtubule cytoskeleton. Many subfamilies of motor proteins exist, but how each of these motor proteins contributes to selective cargo delivery is unknown. I have recently developed an approach to probe specific motor activity inside cells, which revealed that many microtubule-based motors selectively target axons. However, the molecular mechanisms behind this remarkable selectivity are unknown. In addition, it is well-established that most cargos are transported by a combination of different motors, but how the activity of different types of motors on the same cargo is integrated has remained unclear. The aim of this proposal is to understand how motor proteins navigate the neuronal cytoskeleton. We will take a multidisciplinary approach and combine neurobiology, molecular engineering, advanced microscopy, and mathematical modelling to study the origin of motor selectivity as well as the collective activity of dissimilar motor teams. We will employ and expand our unique methodology to: 1) Study how the spatial organization and post-translational modifications of the microtubule cytoskeleton facilitate selective transport. 2) Perform well-controlled intracellular multi-motor assays to understand the functional interplay between different types of motors. Successful achievement of these objectives will uncover key mechanisms of polarized transport, which will be relevant for understanding transport-associated neurodegenerative diseases.

Keywords: polarized transport,microtubules,molecular motors
Designing microProteins to alter growth processes in crop plants (MIPDESIGN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Denmark,Germany
Call:  (ERC-2013-StG, 2013)
Start date: 2013-12-01
End date: 2018-11-30
Duration (months): 60.0
Total project cost (EUR): 1443320.0
EU funding (EUR): 1443320.0
Participants: 2
Project status: CLOSED

The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Mechanisms of social attention (MESA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: The Human Mind and its complexity
Countries involved: Germany,Germany
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-07-31
Duration (months): 66.0
Total project cost (EUR): 1379710.0
EU funding (EUR): 1379710.0
Participants: 2
Project status: CLOSED

A fundamental research question of several disciplines concerns the description, explanation and prediction of human behavior in social contexts. While significant research had been devoted to higher order social capabilities, much less is known about basic principles that are underlying these functions. This is especially true for social attention which is at the heart of every higher order social function but has neither been systematically examined in naturalistic environments before nor has it been linked to the extensive body of psychological and neuroscientific research on basic principles of attention. As a consequence, it is unknown whether the neural computation and the behavioral expression of social attention is similar or divergent to other forms of non-social attention. The current project will fill this gap by comprehensively characterizing the distinctive features of social attention on the behavioral and neural level using a multimodal approach involving eye tracking measures, neuropeptidergic manipulations, fMRI and EEG. I propose that social elements in complex environments are automatically selected and preferentially processed which is mediated by a specialized subcortico-cortical system that allows for tagging social cues in the visual field. These hypotheses will be tested in healthy volunteers and in clinical disorders with well-described impairments in social functioning. Finally, immersive virtual reality environments will be used that allow for examining active behavior and attentional allocation in complex social situations which approximate naturalistic field settings. By highlighting ecological validity, this project will provide unique insights into the mechanisms of social attention in healthy individuals and it will identify maladaptive attentional processes in individuals with impaired social functioning. Building on these data, the proposed research will provide a new framework for understanding human behavior in social situations.

Keywords: attention,social cues,eye tracking,virtual reality,neuroimaging
The role of mechanical forces induced by prenatal movements in joint morphogenesis (MECHJOINTMORPH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Products and process engineering
Countries involved: United Kingdom
Call:  (ERC-2013-StG, 2013)
Start date: 2014-01-01
End date: 2019-12-31
Duration (months): 72.0
Total project cost (EUR): 1499501.0
EU funding (EUR): 1499501.0
Participants: 1
Project status: CLOSED

Most joints start off the same during embryonic development, as two opposing cartilage surfaces, and are moulded into the diverse range of shapes seen in the adult in a process known as morphogenesis. While we understand very little of the biological or mechanobiological processes driving joint morphogenesis, there is evidence to suggest that fetal movements play a critical role in joint shape development. Developmental Dysplasia of the Hip (DDH), where the hip is partly or fully dislocated, is much more common when the baby’s movement is restricted or prevented. This proposal will determine how mechanical forces influence joint shape morphogenesis, which is of key relevance to neonatal joint conditions such as DDH, to adult joint health and disease, and to tissue engineering of cartilage. A mouse line in which mutant embryos have no skeletal muscle will be studied, providing the first in depth analysis of mammalian joint shape development for normal and abnormal mechanical environments. The mouse line could provide the first mammalian model system for prenatal onset DDH. ‘Passive’ movements of these mutant embryos will then be induced by massage of the mother, and the effects on the joints measured. If the effects on joint shape of absent spontaneous movement are mitigated by the treatment, this technique could eventually be used as a preventative treatment for DDH. Next, an in vitro approach will be used to quantify how much movement is needed for joint shape development. This research will provide an optimised protocol for applying biophysical stimuli to promote cartilage growth and morphogenesis in culture, providing valuable cues to cartilage tissue engineers. Finally, a computational simulation of joint shape morphogenesis will be created, which will integrate the new understanding gained from the experimental research in order to predict how different joints shapes develop in normal and abnormal mechanical environments.

Keywords: biomechanics/mechanobiology,cartilage,prenatal joint development,developmental dysplasia of the hip,mechanotransduction,prenatal movements,limb explant in vitro culture,finite element analysis
Metabolic requirements for prostate cancer cell fitness (CANCERMETAB)

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: Spain
Call:  (ERC-2013-StG, 2013)
Start date: 2013-11-01
End date: 2019-10-31
Duration (months): 72.0
Total project cost (EUR): 1498686.0
EU funding (EUR): 1498686.0
Participants: 1
Project status: CLOSED

The actual view of cellular transformation and cancer progression supports the notion that cancer cells must undergo metabolic reprogramming in order to survive in a hostile environment. This field has experienced a renaissance in recent years, with the discovery of cancer genes regulating metabolic homeostasis, in turn being accepted as an emergent hallmark of cancer. Prostate cancer presents one of the highest incidences in men mostly in developed societies and exhibits a significant association with lifestyle environmental factors. Prostate cancer recurrence is thought to rely on a subpopulation of cancer cells with low-androgen requirements, high self-renewal potential and multidrug resistance, defined as cancer-initiating cells. However, whether this cancer cell fraction presents genuine metabolic properties that can be therapeutically relevant remains undefined. In CancerMetab, we aim to understand the potential benefit of monitoring and manipulating metabolism for prostate cancer prevention, detection and therapy. My group will carry out a multidisciplinary strategy, comprising cellular systems, genetic mouse models of prostate cancer, human epidemiological and clinical studies and bioinformatic analysis. The singularity of this proposal stems from the approach to the three key aspects that we propose to study. For prostate cancer prevention, we will use our faithful mouse model of prostate cancer to shed light on the contribution of obesity to prostate cancer. For prostate cancer detection, we will overcome the consistency issues of previously reported metabolic biomarkers by adding robustness to the human studies with mouse data integration. For prostate cancer therapy, we will focus on a cell population for which the metabolic requirements and the potential of targeting them for therapy have been overlooked to date, that is the prostate cancer-initiating cell compartment.

Keywords: cancer metabolism,mouse models,prostate cancer,cellular/molecular biology,cancer therapy,cancer-initiating cell metabolism,obesity,clinical studies,translational research,preclinical studies
Chromosome inheritance from mammalian oocytes to embryos (CHROMHERITANCE)

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: Austria
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2020-01-31
Duration (months): 72.0
Total project cost (EUR): 1499738.0
EU funding (EUR): 1499738.0
Participants: 1
Project status: CLOSED

One of the most dramatic transitions in biology is the oocyte-to-zygote transition. This refers to the maturation of the female germ cell or oocyte, which undergoes two rounds of meiotic chromosome segregation and, following fertilization, is converted to a mitotically dividing embryo. We aim to establish an innovative research program that addresses fundamental questions about the molecular processes controlling the mammalian oocyte-to-zygote transition to ensure faithful inheritance of genomes from one generation to the next. We are taking an interdisciplinary approach combining germ cell and chromosome biology with cell cycle and epigenetic studies to understand how maternal factors regulate chromosome segregation in oocytes and chromatin organization in the zygote. A molecular understanding of key players regulating these processes is a requisite step for investigating how their deterioration contributes to maternal age-related aneuploidy and infertility. Aneuploidy is the leading cause of mental retardation and spontaneous miscarriage. The current trend towards advanced maternal age has increased the frequency of trisomic fetuses by 71% in the past ten years. A better understanding of mammalian meiosis is therefore relevant to human reproductive health. A special feature of the female germ line is that meiotic DNA replication occurs in the embryo but oocytes remain arrested until the first meiotic division is triggered months (mouse) or decades (human) later. The longevity of oocytes poses a challenge for the cohesin complex that must hold together sister chromatids from DNA synthesis until chromosome segregation. We specifically aim to: 1) elucidate how sister chromatid cohesion is maintained in mammalian oocytes, 2) identify mechanisms regulating cohesion in young and aged oocytes, and 3) investigate how the inheritance of genetic and resetting of epigenetic information is coordinated with cell cycle progression at the oocyte-to-zygote transition.

Keywords: fertility
A Diagonal Approach to CO2 Recycling to Fine Chemicals (CO2RECYCLING)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Materials and Synthesis
Countries involved: France
Call:  (ERC-2013-StG, 2013)
Start date: 2013-11-01
End date: 2018-10-31
Duration (months): 60.0
Total project cost (EUR): 1494734.0
EU funding (EUR): 1494734.0
Participants: 1
Project status: CLOSED

Because fossil resources are a limited feedstock and their use results in the accumulation of atmospheric CO2, the organic chemistry industry will face important challenges in the next decades to find alternative feedstocks. New methods for the recycling of CO2 are therefore needed, to use CO2 as a carbon source for the production of organic chemicals. Yet, CO2 is difficult to transform and only 3 chemical processes recycling CO2 have been industrialized to date. To tackle this problem, my idea is to design novel catalytic transformations where CO2 is reacted, in a single step, with a functionalizing reagent and a reductant that can be independently modified, to produce a large spectrum of molecules. The proof of concept for this new “diagonal approach” has been established in 2012, in my team, with a new reaction able to co-recycle CO2 and a chemical waste of the silicones industry (PMHS) to convert amines to formamides. The goal of this proposal is to develop new diagonal reactions to enable the use of CO2 for the synthesis of amines, esters and amides, which are currently obtained from fossil materials. The novel catalytic reactions will be applied to the production of important molecules: methylamines, acrylamide and methyladipic acid. The methodology will rely on the development of molecular catalysts able to promote the reductive functionalization of CO2 in the presence of H2 or hydrosilanes. Rational design of efficient catalysts will be performed based on theoretical and experimental mechanistic investigations and utilized for the production of industrially important chemicals. Overall, this proposal will contribute to achieving sustainability in the chemical industry. The results will also increase our understanding of CO2 activation and provide invaluable insights into the basic modes of action of organocatalysts in reduction chemistry. They will serve the scientific community involved in the field of organocatalysis, green chemistry and energy storage.

Keywords: carbon dioxide,organocatalysis,hydrosilylation,mechanisms,silicon,hydrogen,transition metals,main group elements,coordination chemistry,small molecules activation,density functional theory
Lipid antigens in intestinal inflammation and tumor development (IBDLIPIDS)

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-2013-StG, 2013)
Start date: 2014-01-01
End date: 2019-12-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

Lipids play crucial roles in metabolism, immunity and cancer. In addition to their function as inflammatory mediators, lipids serve as antigens presented by CD1d and activate a subset of T cells called natural killer T (NKT) cells. While NKT cells are critical for human immunity, their uncontrolled activation contributes to inflammatory bowel disease (IBD), a group of diseases characterized by chronic intestinal inflammation and an increased risk of colorectal cancer (CRC). Specifically, NKT cells are the major source of pathogenic TH2 cytokines in the inflammatory bowel disease ulcerative colitis (UC), are sufficient to cause intestinal inflammation in mice, and are required for colitis and colitis-associated cancer in a mouse model of UC. These observations suggest that targeting of lipid antigen presentation may be of therapeutic value in IBD, where current therapies are of limited efficacy and aim at control rather than cure of disease. Here, I propose to identify the lipid antigens responsible for NKT cell-mediated intestinal inflammation and colitis-associated cancer in human IBD and mouse models of intestinal inflammation and to develop therapeutic strategies for interference with pathogenic lipid antigen presentation. Specifically, I propose to characterize the intestinal inflammation- and cancer-associated CD1d lipidome based on novel in vitro and in vivo models of cleavable CD1d and a recently established lipidomics approach. Furthermore, I propose to develop strategies for inhibition of the generation, loading and presentation of inflammation- and cancer-associated lipid antigens. These studies combine biochemical, immunological and high-throughput technologies in an interdisciplinary manner to provide the knowledge required for the generation of novel, efficacious therapies for the treatment of IBD. These studies will have major implications for IBD and other inflammatory, infectious, and neoplastic diseases at mucosal barriers.

Keywords: natural killer t cells,cd1d,lipid antigens,lipidomics,inflammatory bowel diseases,colitis-associated cancer
Multilaser Additive Layer Manufacturing of Tiles (MALT)

Framework: FP7 — Cooperation
Programme: Joint Technology Initiatives (Annex IV-SP1)
Theme: Public-private partnerships
Destination: Clean Sky
Action type: Article 171 of the Treaty
Partnership: CLEAN-SKY (Art-185)
Countries involved: Germany,United Kingdom
Call:  (SP1-JTI-CS-2012-03, 2012)
Start date: 2013-06-01
End date: 2016-12-31
Duration (months): 43.0
Total project cost (EUR): 2399662.79
EU funding (EUR): 1319664.6
Participants: 3
Project status: CLOSED

Laser Additive Layer Manufacturing of tiles in various nickel superalloys has been demonstrated at TRL4. Considerable investment has been made in developing materials data for the processes of record employed on the current generation of equipment, however this equipment is for general purpose prototyping and is not capable of high volume, low cost production of flight parts. The objective of this project is to develop a second generation machine suitable for low cost manufacture while maintaining process equivalence to the current processes of record. This will be achieved by the use of multiple lasers to address a larger build envelope and will otherwise be in line with the capability requirements stated in the topic call. The Participants will first agree the requirements for the machine with the Topic Manager. From this a functional specification will be developed, embodying the essential design concepts to be realised. A test rig will be constructed and operated in order to explore methods for controlling the overlap areas between laser fields. An alpha system will be designed, constructed and tested in accordance with the functional specification and incorporating the learning from the test rig. A subsequent prototype machine, being a development of the alpha machine, will be designed built & tested prior to installation in a representative production environment. Validation testing will be performed on this machine in order to establish (1) metallurgical equivalence to the current processes of record, (2) accuracy, in particular in overlap regions, (3) system reliability and (4) cost of ownership metrics.

Keywords: lean burn combustion liner tiles laser powder bed additive economic manufacturing nickel superalloy high temperature