Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
VERTICAL MICROFLUIDIC PROBE: A nanoliter "Swiss army knife" for chemistry and physics at biological interfaces (BIOPROBE)

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: Switzerland
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1488600.0
EU funding (EUR): 1488600.0
Participants: 1
Project status: CLOSED

Life is fundamentally characterised by order, compartmentalisation and biochemical reactions, which occurs at the right place right time – within, on the surface and between cells. Only a proportion of life processes can be addressed with contemporary approaches like liquid encapsulations (e.g. droplets) or engineering compartments (e.g. scaffolds). I believe these approaches are severely limited. I am convinced that a technique to study, work and locally probe adherent cells & tissues at micrometer distances from cell surfaces in “open space” would represent a major advance for the biology of biointerfaces. I therefore propose a non-contact, scanning technology, which spatially confines nanoliter volumes of chemicals for interacting with cells at the µm-length scale. This technology called the vertical microfluidic probe (vMFP) – that I developed at IBM-Zurich – shapes liquid on surfaces hydrodynamically and is compatible with samples on Petri dishes & microtiter plates. The project is organized in 4 themes: (1) Advancing the vMFP by understanding the interaction of liquid flows with biointerfaces, integrating functional elements (e.g. heaters/electrodes, cell traps) & precision control. (2) Developing a higher resolution method to stain tissue sections for multiple markers & better quality information. (3) Retrieving rare elements such as circulating tumor cells from biologically diverse libraries. (4) Patterning cells for applications in regenerative medicine. Since cells & tissues will no longer be limited by closed systems, the vMFP will enable a completely new range of experiments to be performed in a highly interactive, versatile & precise manner – this approach departs from classical “closed” microfluidics. It is very likely that such a tool by providing multifunctional capabilities akin to the proverbial ‘Swiss army knife’ will be a unique facilitator for investigations of previously unapproachable problems in cell biology & the life science.

Keywords: microfluidics,surface assays,nanobiotechnology,minaturized assays,single cell studies,immunohistochemistry
Role of endoplasmic reticulum in neurodegeneration: physiopathology of a form of hereditary spastic paraplegia as a model (ER-HSP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-04-01
End date: 2018-03-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Endoplasmic reticulum (ER) is a dynamic, tubular intracellular network implicated in a variety of cellular functions. Although it is known to play a role in neurodegeneration, its organization and precise function in neurons have been neglected. I will use the physiopathology of certain forms of hereditary spastic paraplegia (HSP) as a model to understand why and how alteration of ER dynamics in neurons can lead to neurodegeneration. I will focus on three genetic entities, SPG11, SPG15 and SPG48, which are clinically and biochemically related, since the proteins encoded by these genes (spatacsin, spastizin and KIAA0415) are all present in a multiprotein complex important for ER function. The project has three objectives: - Elucidate the role of spatacsin, spastizin and KIAA0415 in the regulation of ER morphology and dynamics; - Establish the link between abnormal ER function and neurodegeneration; - Identify new partners of spatacsin, spastizin and KIAA0415 implicated in ER function. - We will first develop and characterize physiopathological experimental models: (i) an SPG11 knockout mouse; (ii) primary cultures of neurons subjected to RNA interference to downregulate expression of the SPG11, 15 and 48 genes; (iii) neurons differentiated from induced pluripotent stem (iPS) cells derived from fibroblasts of patients with mutations in SPG11, 15 and 48. ER organization and dynamics will be analyzed in these models using electron and fluorescence microscopy (confocal microscopy, super resolution Structured Illumination Microcopy), as well as videomicroscopy on living cultured neurons. The cell culture models will allow us to determine how the functions of ER that are altered in the pathological models in culture are linked to neuronal death. This pioneering work will help understand the functions of neuronal ER in both normal and pathological conditions – HSP, but also other neurodegenerative diseases.

Keywords: hereditary spastic paraplegia,endoplasmic reticulum,neuron,ips cells,imaging,neurodegeneration
Anatomical and Functional Dissection of Neural Circuits in the Zebrafish Optic Tectum (ZEBRATECTUM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2018-06-30
Duration (months): 66.0
Total project cost (EUR): 1920000.0
EU funding (EUR): 1920000.0
Participants: 1
Project status: CLOSED

The optic tectum has emerged as a tractable visuomotor transformer, in which anatomical and functional studies can allow a better understanding of how behavior is controlled by neuronal circuits. We plan to examine the formation and function of the visual system in zebrafish larvae using in vivo time-lapse microscopy and state-of-the-art “connectomic” and “optogenetic” approaches to monitor and perturb neuronal activity. We will apply complementary cellular and molecular analyses to dissect this circuit and identify the neuronal substrate of visual behaviors. We will start by analyzing the function, development and connectivity of a newly characterized class of inhibitory interneurons located in the superficial part of the tectal neuropil named SINs (superficial inhibitory interneurons) that I have previously identified. Our work based on functional imaging has placed SINs at the center of a tectal micro-circuit for size tuning of visual stimuli. We will dissect this working model by analyzing the physiological properties of SINs. We also will investigate their development and connectivity at the level of single synapses by imaging these cells in vivo using fluorescent reporters in transgenic animals. We will then study how SINs migrate to their final position in the superficial tectum away from the zone where they are initially generated and how their processes direct tectal synaptic lamina formation. SINs are the only tectal cells expressing Reelin and we will analyze the role of this pathway in tectal development and proper synaptic lamination in the tectal neuropil. Our multidisciplinary approach aims to describe in great detail the formation and function of a neuronal circuit crucial for visual function, establishing this model for neural circuits studies in vertebrates.

Keywords: tectum,optogenetics,neural circuits,zebrafish.
Learning to read the code of large neural populations (NEURO-POPCODE)

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: Israel
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2018-10-31
Duration (months): 70.0
Total project cost (EUR): 1438996.0
EU funding (EUR): 1438996.0
Participants: 1
Project status: CLOSED

Information is represented and transmitted in the brain by the joint activity of large groups of neurons. Understanding how information is “written” in these population patterns, and how it is read and processed, is a fundamental question in neuroscience. Yet, because of the huge number of potential activity patterns and complexity of natural stimuli, most of our understanding of the code relies on single neuron studies. We will extend and apply mathematical tools from information theory, machine learning, and physics, to overcome this ‘curse of dimensionality’ and build neural dictionaries relating activity and stimuli at an unparalleled resolution of hundreds of neurons. To identify the fundamental design principles of neural population codes we will study the spatial and spatio-temporal activity of hundreds of neurons from the retina, tectum, and cortical networks responding to naturalistic and artificial stimuli. Our primary goals are: (a) to characterize the encoding ‘codebooks’ of large populations of neurons, and the effect of network noise on encoding, and thus construct a thesaurus for neural populations, (b) use this thesaurus to develop new family of decoders of population activity which would be biologically plausible and accurate for natural stimuli, (c) characterize adaptation at the level of the code of networks of neurons, and the effect of learning on population neural codes, (d) explore “learnability” as a key feature of the neural code, and construct biologically plausible models of how the brain can learn to read population codes and compute, and (e) merge these ideas into a new mathematical framework that will connect the architecture of neural interaction networks and the properties of their neural codes. Our work will establish a new mathematical framework for studying the neural code, which will entail important implications for neural prostheses and brain machine interfaces, as well as brain-inspired learning algorithms.

Keywords: neural code,neural populations,networks,information,adaptation,learning,correlation,noise,modeling
Probing organ-level stem cell dynamics on a chip (STEMCHIP)

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: Switzerland
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-12-01
End date: 2017-11-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

More than 30’000 patients with hematological malignancies greatly benefit from hematopoietic stem cell (HSC) transplants each year in Europe alone. However, availability of transplant material for afflicted patients, prognosis, and relapse-free survival are all hindered by the limited quantity of HSCs available for therapy. Despite several decades of research, HSC cannot be cultured in vitro without rapidly differentiating. This is largely due to our poor understanding of the mechanisms that regulate HSC fate in response to cues from their microenvironmental ‘niche’, and the difficulty to unveil these mechanisms using existing experimental model systems. Building on our extensive expertise in the engineering of artificial stem cell niches and microfluidic technology, here I propose to develop a novel in vitro bone marrow model to recapitulate its organ-level function in regulating HSC fate. A modular microfluidic system, termed ‘bone marrow-on-chip’, will be designed comprising a niche compartment, mimicking key anatomical, cellular and molecular characteristics of the HSC niche. This niche compartment will be coupled to a fluidic network, as a simplistic surrogate of the native circulation such as to inject and remove HSC progeny for various analyses. This should allow, for the first time, the in vitro modelling of dynamic physiological HSC processes such as the ‘homing’ of stem cells to the niche after transplantation, and the ‘mobilization’ of stem cells from the niche upon systemic stimulation. With this tool we will be able to gain insight into the cell types and factors found in HSC niches and how they influence HSC behavior in mice and humans, providing paths forward to designing novel HSC expansion procedures. The successful realization of this concept would represent a scientific and technological paradigm shift with impact beyond the field of hematopoiesis, opening up new horizons for the for the study of other stem cell and even tumor cell types.

Keywords: hematopoetic stem cells,niche,bone marrow,self-renewal,expansion,fate choice,transplantation,artificial niche,microfluidics,homing,mobilization,'bone marrow-on-chip'
Probing Druggability of Multisubunit Complexes: E3 Cullin RING Ligases (DRUGE3CRLS)

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-2012-StG_20111109, 2012)
Start date: 2013-05-01
End date: 2018-04-30
Duration (months): 60.0
Total project cost (EUR): 1499904.0
EU funding (EUR): 1499904.0
Participants: 1
Project status: CLOSED

This proposal is centred on the development and application of chemical tools to probe molecular recognition of multiprotein complexes. Although much effort has been devoted to targeting protein-protein interactions using small molecules, these have focused to date on individual gene products or truncated domains, which however do not reflect the physiological organization and activity of many functional proteins. Few successes have been achieved, yet many of the key physical determinants of druggability of surfaces within native protein complexes have remained elusive. The aim of this project is to shed light upon this problem by chemically interrogating biological systems that rely on several subunits working in concert rather than on single proteins working alone. As model system we will investigate the Cullin RING Ligases (CRLs), the largest superfamily of multisubunit E3 ligases in humans. These enzymatic machines are responsible for the recognition, poly-ubiquitination and targeting of substrate proteins to the proteasome for degradation. Many members of this family have crucial roles in cellular physiology and homeostatis, are implicated in a wide range of diseases and are attractive targets for drug discovery. Two interdependent lines of enquiry will be followed. First, we will screen for and elucidate the binding of small molecular fragments and short peptides to identify new druggable surfaces and interfaces on CRLs and their components. Second, we will exploit the nature of the interactions to develop novel chemical probes of CRLs. As the probes are selected and optimised for binding rather than for a particular functional outcome, diverse mechanisms of action are envisaged beyond conventional disruption of the interaction. The successes of this interdisciplinary research will provide a step change in how we interrogate protein-protein interactions of functional and pathological pathways with impact in many areas of chemical biology and drug discovery.

Keywords: chemical biology
Laser: driving force for a new generation of hearing aids (LASERHEARINGAIDS)

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: Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-10-01
End date: 2018-05-31
Duration (months): 68.0
Total project cost (EUR): 1276698.0
EU funding (EUR): 1276698.0
Participants: 1
Project status: CLOSED

This proposal presents an unconventional method for the stimulation of the outer and middle ear that may change the current concept of hearing aids. Photons of the visible light are known to activate the visual sensory cells through photoreceptors. However, when the so-called stress-confinement condition is fulfilled, laser light can induce an acoustic signal through an optoacoustic effect. We demonstrated previously that these light induced sound waves, the optoacoustic waves, can be used to activate the inner ear, the cochlea. Unexpectedly, we found that not just the inner ear but also the middle and outer ear are responsive to laser pulses. However, simple activation of the auditory system is not a sufficient therapy in hearing impaired people. A controlled frequency specific activation of the complete audible frequency spectrum is mandatory to make speech and complex sounds of daily life perceptible and intelligible. The overall objective of this project is to establish methods for frequency specific activation of the complete audible spectrum using monochrome laser pulses. The frequency modulation is a well known process in physics that has to be proven as valid for biological systems as well. Successfull development of parameters for frequency modulation and speech coding resulting will create / provide the basis for a novel non-contact stimulation method that will revolutionize the implantable and non-implantable hearing aids by replacing the speaker or the sound transducer (force mass transducer, the Bone Anchored Hearing Aid screw) with the non contact and focused laser pulses. We expect that the development of these novel stimulation-strategy and stimulation-devices will ameliorate patients’ quality of life by significantly improving their aided hearing and comfort using the hearing device as well as reducing medical health care expenses determined through device related complications.

Keywords: laser,light,hearing,optoacoustic,auditory prostheses
Demonstrating the industrial validity and market feasibility of IT Tool to support SMEs in systematic innovation processes (MARKET IT)

Framework: FP7 — Capacities
Programme: Research for the benefit of SMEs
Destination: Demonstration Activity
Action type: Collaborative project
Countries involved: Italy,Romania,Spain,Romania
Call:  (FP7-SME-2012, 2012)
Start date: 2012-07-01
End date: 2013-12-31
Duration (months): 18.0
Total project cost (EUR): 810976.0
EU funding (EUR): 429000.0
Participants: 5
Project status: CLOSED

The MARKET IT objective is to demonstrate the viability of applying advanced web semantic technologies to SMEs innovation processes. MARKET IT will start from the results achieved in the project TECH-IT-EASY (FP7 Research for the Benefit of SMEs - Grant Agreement number 232410) ended on the 31st of July 2011. The results of TECH IT EASY consist in a prototype information system able to support electromechanical SMEs in the product innovation process. The project will perform technical improvements of the current available software prototype, industrial validation exercises in SMEs, and will define a specific marketing strategy to guide SMEs in the commercial exploitation. The MARKET IT project success will demonstrate the following scientific and technological results: - The availability of a Web semantic driven information system able to deal with weakly structured contents and processes such as the ones related to the overall SMEs innovation-process; - The structuring of the overall SMEs innovation-process through the usage of ontologies as formal way of representing knowledge in a way understandable by machines; - The usage of such formal representation to search and filter relevant information present on the Web and in the SMEs internal knowledge base to support the innovation processes.

Keywords: it tool,innovation,ontologies,semantic web,market strategy
Reverse engineering the vertebrate molecular machinery for magnetic biomineralisation (MAGNETOGENETICS)

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: Germany,Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1469100.0
EU funding (EUR): 1469100.0
Participants: 2
Project status: CLOSED

In order to understand distributed biological networks and invent effective molecular therapies, we need to be able to image and control molecular processes across entire live organisms. Although an arsenal of genetically encoded fluorescent sensors and light-activated proteins has recently been developed to visualize and manipulate cellular activity, these methods all suffer from the poor penetration of light through biological tissue, which makes them rather invasive for practical in vivo use in animal models and prevents whole-organ coverage. To overcome these substantial limitations of optical methods, I thus propose a reverse engineering project to functionally dissect the molecular machinery for magnetic biomineralisation in eukaryotic cells and build a new bioengineering platform for genetically controlled bio-magnetic interfaces. To achieve this goal, we will use a combination of magnetic cell sorting and biophysical characterization, targeted analysis and -omics approaches as well as genetic tools. This scientific program will break the ground for non-invasive sensing and actuation of molecular processes via magnetic fields based on genetic control over the biosynthesis of magnetic biominerals.

Keywords: bioengineering,protein engineering,cellular control,molecular imaging