Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Regulation and function of linear ubiquitination by HOIP (LUBI)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Austria
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-07-01
End date: 2020-06-30
Duration (months): 72.0
Total project cost (EUR): 1997908.0
EU funding (EUR): 1997908.0
Participants: 1
Project status: CLOSED

Ubiquitin (Ub) is a small protein modifier, regulating diverse biological functions such as signalling, DNA repair and proteasomal degradation. Ub can form polymers via 7 Lys residues of Ub itself. Recently, we have discovered that an E3 ligase complex, Linear Ubiquitin chain Assembly Complex (LUBAC) generates a novel type of Ub polymer linked via Met-1, ‘linear Ub chain’ and regulates NF-kB signalling in mice. Because linear Ub is unique and the study of it is still in infancy, the only E3 ligase known is LUBAC, comprising a catalytic protein HOIP, and two regulatory subunits SHARPIN and HOIL-1L. We have shown that SHARPIN deficiency leads inflammation in mice. A mutation in HOIL-1L gene of human was shown to lead immunodeficiency. Yet, the regulatory mechanisms of HOIP catalytic activity and the biological implications remain poorly understood. Here, we aim to - Elucidate the roles of HOIP in Drosophila - Elucidate the roles of ubiquitination and ligase activities of mammalian HOIP in vivo - Identify novel substrates of human HOIP and clarification of their roles We recently identified an orthologue of HOIP in Drosophila, yet its genome does not encode SHARPIN or HOIL-1L. We aim to elucidate how dmHOIP mediates linear ubiquitination in the absence of regulatory subunits and the roles of HOIP in the NF-kB signalling by genetically deleting HOIP in Drosophila. We further aim to elucidate the role of HOIP E3 ligase activity and ubiquitination in inflammation by generating the conditional knockin mice of HOIP mutants. Moreover, we will develop a protein chip assay to identify new substrates of HOIP and determine how they contribute to the biological functions. Since Ub plays such a wide variety of pathological functions including cancer, inflammation and neuronal diseases, I believe the expected results not only will lead to a better understanding of functional role of HOIP but will also identify novel aspects of linear ubiquitination in human diseases.

Keywords: ubiquitin,linear chain,e3 ligase,hoip,substrates,mouse models,drosophila models
Predicting environment-specific biotransformation of chemical contaminants (PRODUCTS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Medical Biotechnology
Countries involved: Switzerland
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-06-01
End date: 2019-05-31
Duration (months): 60.0
Total project cost (EUR): 1996352.0
EU funding (EUR): 1996352.0
Participants: 1
Project status: CLOSED

The ability to predict rates and products of microbial biotransformation for a broad variety of chemical contaminants accurately is essential not only for chemical risk management but also in the context of contaminated site remediation or the development of green chemical alternatives. Existing prediction methods, however, fall short of fulfilling these needs mostly because they base predictions on chemical structure only, disregarding the microbial communities responsible for degradation and their actual metabolic potential as shaped by environmental conditions. The long-term goals of the proposed research are to develop the scientific basis and appropriate modeling algorithms for considering the metabolic potential of environmental microbial communities (i.e., the available pools of catalytic enzymes) in biotransformation prediction. It is proposed that enzyme-catalyzed biotransformation reactions are established as the explicit core elements of biotransformation prediction. The reactions so defined will serve as mechanistic basis to (i) experimentally explore the linkage between microbial community gene expression profiles and their observed potential for contaminant biotransformation, and (ii) use chemometrics and pattern analysis in high-dimensional space to mine environment-specific chemical biotransformation data for probabilities of biotransformation reactions. The resulting novel algorithms for the environment-specific prediction of biotransformation rates and products will be implemented into an existing, publically-accessible biotransformation prediction system (http://www.umbbd.ethz.ch/predict). The proposed research is highly interdisciplinary and will profit from the most recent technological and scientific advances in the fields of analytical chemistry, molecular biology and chemo-/bioinformatics to develop a ground-breaking approach for profiling the capacity of microbial communities for contaminant biotransformation.

Keywords: structure-biodegradability prediction,transformation products,persistence,chemical risk assessment,xenobiotics,microbial metabolism,metatranscriptomics,functional genomics
Advancing the Study of Chemical, Structural and Surface Transformations in Colloidal Nanocrystals (TRANS-NANO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Synthetic Chemistry and Materials
Countries involved: Italy
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 2430720.0
EU funding (EUR): 2430720.0
Participants: 1
Project status: CLOSED

Colloidal inorganic nanocrystals (NCs) are among the most investigated nanomaterials in Nanoscience due to their high versatility. Research on NCs went through much advancement lately, especially on synthesis, assembly and on the study of their transformations, most notably via cation exchange (all fields in which the PI has contributed already). However, the integration of NCs with fabrication tools that employ conditions such as irradiation, etching and annealing is at a very early stage since we do not have a systematic knowledge of what transformations are triggered in the NCs under those conditions. Also, an issue related to the incorporation of NCs in materials/devices is whether, over time, the NCs will remain as they are, or they will transform into other structures. Plus, these transformations in NCs are poorly studied as they require fast recording techniques. This proposal will embark on an ambitious investigation of post-synthetic transformations in solution-grown NCs: by advancing the understanding of various aspects of chemical, structural and surface transformation of NCs, we will uncover new fabrication techniques that will employ such nanostructures as the key ingredients. This in turn will have a strong impact in opto-electronics, as several electronic components entirely made of NCs will be delivered. Four objectives are targeted: i) developing radically new sets of experimental tools for the investigation of chemical transformations in NCs, above all the ability to monitor in real time these transformations; ii) developing solution-grown nanostructures able to undergo programmed transformations under a defined stimulus; iii) understanding the role of irradiation on the fate of surface ligands and on cation exchange reactions in NCs; iv) combining chemical, structural and surface transformations towards NC-based opto-electronics. The success of the proposal hinges on the proven capabilities of the PI, with ample support from the host Institution.

Keywords: nanocrystals,transformations,cation exchange,annealing,irradiation
A systems pharmacology approach to the discovery of novel therapeutics in Alzheimer´s disease (SYSPHARMAD)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Spain
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-09-30
Duration (months): 66.0
Total project cost (EUR): 1296000.0
EU funding (EUR): 1296000.0
Participants: 1
Project status: CLOSED

Alzheimer´s disease (AD) is the most common form of dementia, with over 35 million people suffering from it worldwide, and it constitutes a personal and societal tragedy of immense proportions. Fifty years of intense research have revealed many key elements of the biology of this neurodegenerative disorder. However, our understanding of the molecular bases of the disease is still very limited, and the available medical treatments for AD are purely symptomatic and hardly effective. It is now clear that the modulation of a single target is unlikely to yield the desired outcome, and we should move from gene-centric to network-centric therapeutic strategies. In addition, we should focus on early (asymptomatic) phases of AD, before the brain damage is irreversible, and the identification of molecular biomarkers to monitor the response of patients is paramount. Accordingly, the main objective of our proposal is the identification of novel biomarkers in AD to monitor the onset and progression of the pathology from very early stages, and to discover combinations of drug targets and chemical compounds able to modify the biology of the disease. We will first run proteomics and transcriptomics experiments, in AD mouse models, to reveal the organization of proteins and genes that are up- or down-regulated at different ages and AD stages, and their potential translocation into/out of mitochondria. We will then construct the AD-associated network, incorporating clinical data, which we will use as a framework for the integration and analyses of the –omics data collected. We will transform the static data snapshots, corresponding to the different AD stages, into a dynamic model able to explain the progression of the disease, providing hints as to the best strategies to monitor and modulate AD evolution. We will finally design and validate a systems pharmacology strategy, based on concerted multi-target perturbations with small molecules, to modify the biology of the disease.

Keywords: network biology,network medicine,polypharmacology
Scaling-up multiphase microchemical reactors (MICROTOMILLI)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Belgium,United Kingdom
Call:  (FP7-PEOPLE-2013-CIG, 2013)
Start date: 2013-10-01
End date: 2017-10-25
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

The aim of chemical engineering and its unit operations is to transform raw materials into products (e.g. commodity and specialty chemicals like pharmaceuticals). However, motivated by the awareness of the world’s finite resources, it is desirable that these products are obtained in a sustainable, efficient and environmentally acceptable fashion, which means minimising waste and energy use, and make increasingly use of renewable raw materials. Novel efficient manufacturing technologies, flexible chemical plants, integrated process development, and innovative design approaches will provide the solutions to this important challenge. To reach these goals further research efforts in process intensification are needed, and there is also the demand for novel concepts for continuous reaction systems. Furthermore, many of the relevant chemical transformations involve multiphase flow, either gas-liquid, immiscible liquids, or solid-liquid. Thus, to successfully design these novel continuous reaction systems a detailed understanding of multiphase flow systems and the underlying physics of the transport processes associated with the various length scales is needed. Therefore, the aim of the proposed research is to understand interfacial transport processes and the scale-up of the involved transport coefficients in more detail. This is accomplished by identifying the physical mechanisms of heat and mass transfer on the micro- and milli-scale using non-invasive, laser-optical measurement techniques, and to use these experimental results to develop predictive multiphase flow models for computational fluid dynamics (CFD). The obtained results will bridge the gap between the micro- and milli-scale, and will directly impact the efforts in process intensification and sustainable advanced manufacturing.

Keywords: process intensification,multiphase flow,microfluidics,advanced manufacturing,piv/lif,cfd
The Leukemia-Initiating Cell: Genetic Determinants, Escape Mechanisms and Ontogenic Influence (LEUKEMIABARRIER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Sweden
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-07-01
End date: 2019-06-30
Duration (months): 60.0
Total project cost (EUR): 1999714.0
EU funding (EUR): 1999714.0
Participants: 1
Project status: CLOSED

Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults and strongly associated in incidence to advanced age. AML arises from immature hematopoietic progenitor cells via a sequential multistep process, but the nature of these steps remains to a large extent unknown. Therefore, while significant efforts have previously been invested in characterizing the molecular properties of late-stage AML, as diagnosed in patients, less information is available on the events that underlie leukemia initiation and progression. This includes the identity of potential mechanisms that restrict or eradicate developing leukemic cells; hurdles evaded at some point in time for AML to occur. We have developed an inducible transgenic mouse model of AML that, when combined with high-resolution cell fractionation of primitive hematopoietic progenitor cells, offers a unique opportunity to track development of AML from the very first stages of cancer development. Using this, I propose to: 1) Identify and functionally validate molecular determinants that underlie why only some hematopoietic progenitor cells progress into AML, 2) To explore the extent and identity of immune surveillance/editing that accompany progression into AML, and 3) By building on my previous work on hematopoietic aging, to explore AML progression in the context of aging. I anticipate the LEUKEMIABARRIER project to generate novel basic knowledge, not excluding with clinical relevance, with the potential to open up several new fields for further studies. This includes identification of novel cell-intrinsic regulators and immune responses, their underlying mechanisms, and their relationship to the increased incidence of AML with age.

Keywords: stem cells,hsc,leukemia,ageing,cancer
Efficient Resource Constrained Cryptography (ERCC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Computer Science and Informatics
Countries involved: Germany,United States
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-11-01
End date: 2019-10-31
Duration (months): 60.0
Total project cost (EUR): 1874960.0
EU funding (EUR): 1874960.0
Participants: 2
Project status: CLOSED

Traditionally, cryptographic protocols were run on servers or personal computers which have large and easily scalable computational resources. For these applications there exist a large variety of well-established cryptographic systems. Right now, we are in the midst of the shift toward ubiquitous computing on resource constrained devices (RCDs): small devices with severe constraints in terms of computing power, code size, and network capacities. RCDs are used virtually everywhere: smart phones, bank cards, electronic ID-cards, medical implants, cars, RFIDs as bar code replacement, etc. Due to their computational constraints, many current cryptographic security solutions are no longer applicable to RCDs. Existing solutions are often “ad-hoc” and do not come with a formal security treatment. The central objective of the ERCC project is to initiate an overarching formal treatment of cryptographic solutions for RCDs, particularly focusing on efficiency. The main conceptual novelty is to follow the concept of provable security. We intend to design new cryptographic protocols that have a mathematical proof of security (assuming the hardness of some mathematical problem) and are still competitive with constructions currently used on RCDs. While we certainly cannot hope that all our new provably secure constructions will be superior to existing ad-hoc constructions, recent preliminary research results give rise to optimism. Concretely, we will base our new protocols on hard problems in ideal and structures lattices and we will study weaker (yet still realistic) security models for RCDs allowing for efficient instantiations.

Keywords: cryptography,provable security,design and analysis of protocols,resource constrained devices,rfid,authentication
Computational Modeling and Design of Lithium-Ion Batteries (COMBAT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Products and Processes Engineering
Countries involved: Germany
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-06-01
End date: 2019-05-31
Duration (months): 60.0
Total project cost (EUR): 1975071.0
EU funding (EUR): 1975071.0
Participants: 1
Project status: CLOSED

Lithium-ion batteries (LIBs) are among the most promising solutions for energy storage. Compared with other resources such as bio-fuel, solar cells, fuel cells or lead acid batteries, rechargeable batteries are more portable and allow for quick energy storage and release. The higher power and energy density make batteries suitable as the energy resource for most portable elect. devices including future vehicles. Among the rechargeable batteries, LIBs have the most potential because of their quick charging rate and high power and energy density. However, ageing of LIBs and the related capacity and power fade is a major concern. For the improvement and future development of batteries, computational modeling and design is an important complementary part to experimental testing which is expensive, time-consuming and sometimes unfeasible. In this project, the PI proposes to develop, implement, verify and validate a computational multifield and multiscale framework to support the design and optimization of new batteries. The computational framework will support the design and optimization of new anode, separator and cathode materials as well as their structure inside the battery. The measurable outcome of this research will be an open-source software package that can be used to support the design and optimization of LIBs. Within the computational framework, different (mechanical-thermal-electro-chemical) fields will be linked over multiple scales: from fundamental physics to the design of new battery materials. We will quantify uncertainties in order to provide upper and lower bounds of our predictions and use graph-theory, error-estimation and adaptivity to choose the appropriate model and discretization. The computational framework will be verified and validated by comparison to experiments. Finally, multi-objective optimization over multiple scales will provide a new battery prototype that will be manufactured, tested and compared to the computational predictions.

Keywords: batteries,computational mechanics,finite elements,partial differential equations,multiscale modeling,multifield modeling,modeling and simulation
Functional analysis of uncultivated microbes using radioisotope probing (MICRO-RIP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Medical Biotechnology
Countries involved: Finland
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-03-01
End date: 2019-06-30
Duration (months): 64.0
Total project cost (EUR): 1997912.8
EU funding (EUR): 1997912.8
Participants: 1
Project status: CLOSED

Environmental microbiology calls for more advanced research methods for resolving microbial functions and regulation in environmental samples. The proposed project introduces an unconventional technology, radioisotope probing (RIP). This approach is based on the invention of radioactivity measurement via pH analysis. When the analysis of radioactivity is now combined with semiconductor sequencing, the technology offers two-dimensional analysis of millions of molecules on a sequencing chip. Hybridization of experimentally labeled RNA and radioactivity measurement would provide a second dimension for the sequencing analysis, facilitating various new applications in environmental microbiology, as well as potential applications for different needs of biochemistry and medical research. The project aims to develop and test three novel RIP applications to analyse functional diversity, transcriptional regulation and mRNA processing in microbial communities, especially focusing on prokaryotic species. The applications are utilized for studying regulation of microbial decomposition, which is the key question, when predicting the effects of climate change. It is hypothesized that more frequent flood, droughts and redox fluctuations can prime the biodegradation of otherwise stable boreal carbon pools. Functional diversity of microbes utilizing model and complex substrates is studied in terrestrial and aquatic environments using time-series samplings and labeling experiments. Prevailing mechanisms in the cellular regulation in microbial communities are investigated using community-level methylation and regulatory RNA patterns. The effect of external stressor (toxicants and changing oxygen regimes) on these patterns is analyzed using sequencing and RIP to reveal the mechanisms regulating the processes beyond mere community composition.

Keywords: microbial processes,carbon cycling,biodegradation,priming,communities,phyologenetics,physiology,epigenetics,regulation,ecosystems biology,boreal peatlands,dissolved organic carbon