Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Role of the transcription factor ChREBP and its associated proteins in the development and progression of NAFLD. (LIPIDOLIV)

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-2013-StG, 2013)
Start date: 2014-02-01
End date: 2020-01-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Changes in lifestyle have resulted in a dramatic epidemic of type 2 diabetes and obesity. Among associated complications, Nonalcoholic Fatty Liver Disease (NAFLD) is emerging as the most common chronic liver disease and is gaining increasing recognition as a component of the epidemic of obesity. NAFLD is generally asymptomatic, although a minority of patients may present progressive liver injury with complications of Nonalcoholic steatohepatitis (NASH), cirrhosis and HCC. Excessive accumulation of fatty acids (FA) stored as triglycerides (TGs) in hepatocytes is the hallmark of NAFLD, which is strongly associated with insulin resistance (IR). However, despite the existing correlation between fatty liver and insulin resistance, it remains unclear whether insulin resistance causes the excessive accumulation of TG in the liver, or whether the increase in TG itself or other lipid intermediates such as diacylglycerols (DAG) and/or ceramides may trigger the development of hepatic or systemic insulin resistance. While some studies support the concept that intrahepatic accumulation of lipids precedes insulin resistance, others suggest that hepatic TG may in fact protect the liver from lipotoxicity by buffering the accumulation of FA. Such discrepancy might be explained since different pools of lipids exist within cells and only certain pools regulate insulin signaling. Consistent with such hypothesis, recent results by our group strongly support that specific FA species may influence hepatic TG storage, insulin signaling and/or inflammation. Therefore, the global aim of our proposal is to better understand the regulation of hepatic fatty acid synthesis and partitioning in addition to its impact on the detailed lipid profile. Using state-of-art technology and key genetically modified mouse models combined with original nutritional approaches and lipidomic analysis, our project aims at providing new information on the molecular basis of the pathogenesis of NAFLD.
Molecular neurobiology of a moonlight entrained circalunar clock (LUNAR.CLOCK)

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: Austria
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-12-31
Duration (months): 71.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Numerous scientific studies have established that the lunar cycle synchronizes reproductive behaviour and sexual maturation of animals as diverse as corals, polychaetes and fishes. Classical and recent work shows that in animals such as the annelid Platynereis dumerilii, dim nocturnal light serves as entrainment cue for an endogenous oscillator – a circalunar clock – that orchestrates reproductive and behavioral cycles. As circalunar clocks run with a (semi-)monthly period, they represent a fundamental biological phenomenon clearly distinct from the widely studied, solar light-entrained circadian (24h) clocks. Despite the vital importance of circalunar clocks, very little is known about the underlying molecular processes and responsible neuron types. This knowledge gap reflects the fact that until now, no suitable model system has been available to study circalunar clocks on the molecular and cellular level. This proposal takes full advantage of the recent establishment of substantial molecular resources and critical techniques for functional analyses in Platynereis, as well as our pioneering work on the first circalunar clock-regulated genes and the identification of four molecular candidates for the nocturnal light receptor. This now allows us to tackle two fundamental objectives: First, we aim to discover the molecular and cellular nature of the lunar light sensor(s) and their interplay with solar light photoreceptors. Second, we aim to characterize circalunar oscillatory genes and their associated neuron types that will pave the way to unravel the molecular and cellular nature of the circalunar oscillator. This work will provide new mechanistic insight into an unexplored biological mystery- circalunar clocks and their regulation by light. It also offers new conceptual advance into how animals accomplish the separation of diurnal versus nocturnal light information for the synchronization of reproductive behaviour, a challenge common in the natural environment.

Keywords: chronobiology
Cultured Liver Organoids for Investigation and Treatment of Inherited Cholestatic Diseases (CLOC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
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): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Bile synthesis and secretion are crucial to liver function and involve multiple proteins. Disorders due to defects in this process (Inherited Cholestatic Disorders, ICDs) lead to progressive liver disease. Many ICD patients do not respond to medical treatment and need liver transplantation (LT). Although ICDs are rare, multifactorial cholestatic diseases are common and many patients will benefit from ICD research. There is acute shortage of liver donors. 10% of patients die while waiting on the liver transplant list. Therefore alternatives to LT are urgently needed. Bioengineered tissues may reduce the need for donor organs but complexity of it's organisation makes generation of functional liver challenging. The OBJECTIVE of this project is to generate Cultured Liver Organoids (CLOs) using hepatocytes cultured on 3-D scaffolds as novel models for study of liver development and disease and potential treatment of ICDs. 3-D extracellular matrix (ECM) scaffolds derived from decellularised livers and polymeric matrices (PM) have been used to mimic liver architecture but further work is needed to establish functional bile flow. Human Induced Pluripotent Stem Cells (hIPSCs) derived from reprogrammed skin fibroblasts by overexpression of pluripotency factors can proliferate and be differentiated into various cell types including hepatocytes. hIPSCs enable production of patient specific cells, which are fully immuno-compatible. Genetically corrected mutant hIPSCs differentiated into hepatocytes have been used as cell therapy in animal models of inherited metabolic disorders but direct infusion of hepatocytes into the liver is unlikely to achieve polarised bile flow and correct ICDs. Therefore hIPSCs developed from ICD patients will be used to culture hepatocytes on decellularised mouse liver ECM to generate in vitro models of ICDs. CLOs containing hepatocytes from genetically corrected hIPSC will be tested in mouse models of ICDs as potential treatment.

Keywords: cholestatic diseases
DRAGNET: A high-speed, wide-angle camera for catching extreme astrophysical events (DRAGNET)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Universe sciences
Countries involved: Netherlands,United Kingdom
Call:  (ERC-2013-StG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 1964587.0
EU funding (EUR): 1964587.0
Participants: 3
Project status: CLOSED

Looking up on a starry night, it’s easy to imagine that the Universe is unchanging. In reality, however, the Universe is teeming with activity: there are massive explosions from accreting black holes, bright radio flashes from ultra-magnetic pulsars, and likely other spectacles that have so far escaped our prying eyes. These fleeting events can happen faster than the blink of an eye and, importantly, they trace the most extreme astrophysical phenomena. Catching these rare performances poses a major challenge for observational astronomers, but the scientific payoff is well worth the effort. With this proposal, I will mould the Low-Frequency Array (LOFAR) telescope into DRAGNET, the world's premier high-speed, wide-angle camera for radio astronomy. Radio waves are a unique and powerful way of investigating the most extreme astrophysical processes. With DRAGNET I will characterize the rate of fast radio transients, i.e. astrophysical bursts lasting less than a second, and search for new astrophysical phenomena in this largely unexplored domain. This has the potential to give us transformative insight into the extremes of gravity and dense matter. Alongside this, I will simultaneously monitor hundreds of radio-emitting neutron stars (pulsars) on a regular basis. This will allow me to understand why some neutron stars pulse regularly, while others show rapid switches in their emission properties. This will address the physics behind the strongest magnetic fields in the Universe. I have led the construction of LOFAR's high-time-resolution observing capabilities; in this project I will capitalize on that investment and do cutting-edge science that is beyond the reach of any other existing telescope. Simply put, this project will establish a world-leading research group in the emerging field of fast radio transients and will crystallize the wide-field radio telescope as an essential tool for unveiling the bustling activity that makes our Universe so interesting to study.

Keywords: pulsar,neutron star,lofar,fast transient,radio astronomy
The role of parvalbumin interneurons in cognition and behavior (COGOPTO)

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: Sweden
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1400000.0
EU funding (EUR): 1400000.0
Participants: 1
Project status: CLOSED

Cognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction. Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators. However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function. The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced. We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.

Keywords: attention,working memory,in vivo optogenetics,synchrony,behavior,inhibition,parvalbumin,gamma,theta,coherence,delatyed-aleternation,5-csrtt
Therapeutic Mechanisms and Long Term Effects of Directed Transcranial Alternating Current Stimulation in Epileptic Seizures (OSCILLINTERFERENCE)

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: Hungary
Call:  (ERC-2013-StG, 2013)
Start date: 2013-11-01
End date: 2018-10-31
Duration (months): 60.0
Total project cost (EUR): 1419000.0
EU funding (EUR): 1419000.0
Participants: 1
Project status: CLOSED

A significant proportion of patients with epilepsy are refractive to pharmaceutical treatments. Recurrent, untreated epileptic seizures are associated with risk of adverse neurological, cognitive, and psychological outcomes. Despite years of study, there are still significant barriers to the management of these disorders. In my proposal I advance the hypothesis that time-targeted perturbation of neural network oscillations by transcranial electric stimulation (TES) decreases the duration of seizures. I hypothesize further that spatially focused TES and chronically applied TES intervention can also permanently reduce seizure occurrence. Our specific aims are designed to perform in vivo studies in rodent models of two seizure types (absence seizures and complex partial seizures) to evaluate the effectiveness of TES in abrogating pathologic network activity, and to use high resolution recording techniques and optogenetical methods to assess the neural mechanisms involved. Our results may help to establish general principles of the diverse epilepsy pathophysiology and introduce novel therapeutic approaches. We will establish a focal TES stimulation protocol to selectively interfere with brain regions previously identified as key structures in the pathomechanism of epilepsy. The deliverables of these experiments will make a significant advancement in the understanding of the pathomechanisms of these disorders, and will offer a new alternative treatment option as a complimentary therapeutic approach to the state of the art pharmaceutical products. The methods used in this project are unique and advanced as the first attempt to perform 512 channel extracellular recordings in the behaving animal to investigate the evolution of epileptic seizures at the neuronal network and cellular levels and by achieving spatially selective TES. The combination of these methods are deployed for both understanding the mechanisms of seizure evolution, and termination of seizures.

Keywords: epilepsy,transcranial alternating current stimulation,optogenetics,spike-and-wave,thalamocortical,hippocampus,temporal lobe,seizure suppression
The Archaeology of Agricultural Resilience in Eastern Africa (AAREA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: The study of the human past
Countries involved: United Kingdom,United Kingdom
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2018-01-31
Duration (months): 48.0
Total project cost (EUR): 1196701.0
EU funding (EUR): 1196701.0
Participants: 2
Project status: CLOSED

The twin concepts of sustainability and conservation that are so pivotal within current debates regarding economic development and biodiversity protection both contain an inherent temporal dimension, since both refer to the need to balance short-term gains with long-term resource maintenance. Proponents of resilience theory and of development based on ‘indigenous knowledge’ have thus argued for the necessity of including archaeological, historical and palaeoenvironmental components within development project design. Indeed, some have argued that archaeology should lead these interdisciplinary projects on the grounds that it provides the necessary time depth and bridges the social and natural sciences. The project proposed here accepts this logic and endorses this renewed contemporary relevance of archaeological research. However, it also needs to be admitted that moving beyond critiques of the misuse of historical data presents significant hurdles. When presenting results outside the discipline, for example, archaeological projects tend to downplay the poor archaeological visibility of certain agricultural practices, and computer models designed to test sustainability struggle to adequately account for local cultural preferences. This field will therefore not progress unless there is a frank appraisal of archaeology’s strengths and weaknesses. This project will provide this assessment by employing a range of established and groundbreaking archaeological and modelling techniques to examine the development of two east Africa agricultural systems: one at the abandoned site of Engaruka in Tanzania, commonly seen as an example of resource mismanagement and ecological collapse; and another at the current agricultural landscape in Konso, Ethiopia, described by the UN FAO as one of a select few African “lessons from the past”. The project thus aims to assess the sustainability of these systems, but will also assess the role archaeology can play in such debates worldwide.

Keywords: geoarchaeology,archaeobotany,intensive agriculture,sustainability,resilience,agent based modelling,east africa.
Spatio-temporal specificity of miRNA function (MIRSPECIFICITY)

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: Austria
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2020-01-31
Duration (months): 72.0
Total project cost (EUR): 1499458.0
EU funding (EUR): 1499458.0
Participants: 1
Project status: CLOSED

MicroRNAs are versatile regulators of gene expression and as such, they are essential parts of the gene regulatory networks controlling development and physiology of animals and plants. In particular, a number of miRNAs have been implicated in cell-type differentiation. Adding miRNAs to existing networks in particular subsets of cells can increase the complexity of developmental programs, and thus contribute to the vast diversity of cell types found in complex multicellular organisms. In order to achieve this function, miRNAs have very diverse and highly specific spatio-temporal patterns of expression. Understanding, when and where miRNAs are expressed and how their expression is regulated is essential to place them in the correct cellular context and grasp their contribution to normal development and disease. miRNA expression can be regulated at the transcriptional and post-transcriptional levels. While transcriptional regulation is known to generate distinct patterns of miRNA production, the contribution of post-transcriptional regulation of miRNA biogenesis and function to their spatio-temporal specificity is virtually unexplored. A few RNA binding proteins have been shown to affect miRNA biogenesis mostly in cell culture yet with one exception, none have been studied in the context of a whole developing organism where their roles in providing specificity to miRNA function could be assessed. Furthermore, only a handful of miRNAs are known to be post-transcriptionally regulated in tissue or stage-specific manners, mostly in organisms not amenable to genetic analysis, thus making it difficult to identify the underlying mechanisms. I propose to use the genetic model system C. elegans to bridge these two stunted approaches. We will identify post-transcriptional regulators of miRNA biogenesis and activity and dissect their contribution to generating specific spatio-temporal domains of miRNA function and in doing so, increasing cell-type diversity.
Single Molecule Nano Electronics (SIMONE) (SIMONE)

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: Sweden
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-11-30
Duration (months): 70.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

The development of micro fabrication and field effect transistors are key enabling technologies for todays information society. It is hard to imagine superfast and omnipresent electronic devices, information technology, the Internet and mobile communication technologies without access to continuously cheaper and miniaturized microprocessors. The giant leaps in performance of microprocessors from the first personal computing machines to todays mobile devices are to a large extent realized via miniaturization of the active components. The ultimate limit of miniaturization of electronic components is the realization of single molecule electronics. Due to fundamental physical limitations, single molecule resolution cannot be achieved using classical top-down lithographic techniques. At the same time, existing surface functionalization schemes do not provide any means of placing a single molecule with high precision at a specific location on a nanostructure. This project has the ambitious goal of establishing the first method ever allowing for self-assembly of multiple single molecule devices in a parallel way and thereby provide the first method ever allowing for multiple individual single molecule components to operate together in the same device. The impact of the technology platforms described herein goes vastly beyond the field of single molecule electronics and utilization in ultra-sensitive plasmonic biosensors with a digital single molecule response will be explored in parallel with the main roadmaps of the project.