Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RASImmune (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Mutations in RAS oncogenes are responsible for driving some 20% of all human malignancies, occurring in many major killers, such as lung, pancreatic, and colon cancers, but attempts to develop therapeutic interventions for RAS mutant cancers have yet to provide clinical benefit. By inhibiting pathways downstream of RAS along with other key signaling nodes, we have developed combination therapies that cause major regression of KRAS mutant lung cancer in mouse models. However, a major limitation is that the tumours are not eradicated and rapidly recur once treatment is withdrawn. Lung cancer is partly responsive to immunotherapies in the clinic, suggesting dependence on immune evasive signaling. We would like to understand whether RAS driven oncogenic signaling pathways act to protect tumours from the immune system. If so, what mechanisms does RAS use to evade tumour immune destruction and can these be specifically targeted to unleash the immune system on the tumour? Could we develop effective therapies rationally combining these with our existing RAS pathway therapies to achieve complete tumour eradication? We will use clinical samples to establish whether activation of RAS signaling pathways correlates with the ability of lung tumours to evade the immune system and by what mechanisms. We will develop appropriate preclinical models to test the impact of targeting immune evasion in RAS driven lung cancer, recognising the major limitations of existing mouse models for this purpose. We will also utilize these immunogenic preclinical models to seek novel mechanisms of tumour immune evasion, including through the use of in vivo functional genomic screens. Finally, we will establish how our existing optimal strategies for achieving RAS signaling pathway inhibition in lung cancer impact on the tumour immune microenvironment and establish strategies for combining these with interventions to subvert immune evasion, thus enabling optimal immune-assisted tumour destruction.

Mots-clés : lung cancer,targeted therapy,immunotherapy
Projet ERC : Stress Imaging (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University Medical Center Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMCG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1454713.75 €

My goal is to optically detect the magnetic resonance of free radicals/ROS inside cells. Radicals are suspected to play a crucial role in numerous pathogenic conditions including diseases responsible for most deaths worldwide (as arteriosclerosis, cancer, immune responses to pathogens). They are also involved in many processes in healthy cells as mitochondrial metabolism or aging of cells and part of the working mechanism of many drugs. Despite their relevance relatively little is known about where and when radicals are built, how they work or which ones play a role. Their short lifetime and reactivity poses a problem for many state of the art methods. Thus they are often a bottleneck in understanding stress responses. My goal is to develop a method, which can detect their magnetic resonance in the nanoscale. The method is based on a fluorescent defect in diamond, which changes its optical properties based on its magnetic surrounding. While this technique has been able to detect even the faint signal of a single electron spin, this technique is entirely new to biological fields. We can localize where, when and how much of a certain radical is generated with nm resolution. This is impossible with the current state of the art. Furthermore, since we obtain spectra we can also differentiate radicals to some extent. I am proposing to investigate two systems: 1) the involvement of radicals in the aging of yeast cells 2) the response of macrophages to stress. In the first project I will test the so-called free radical theory, which states that organisms age because cells accumulate free radical damage over time. In the second project I will answer the question how a macrophage reacts to the impact of a pathogen or a drug. Outcomes of this project would enable us to increase our understanding on how stress responses work on a molecular level. This will open up new possibilities to assess if and how drugs are working or how and why certain pathogens are worse than others.

Mots-clés : imaging,free radicals,nv centers,diamond
Projet ERC : GReatLaP (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

My objectives consist of laying new foundations for the representation theory of p-adic groups and making significant progress on the local, global and relative Langlands program. The Langlands program is a far-reaching collection of conjectures that relate different areas of mathematics including number theory and representation theory. Work in this area has also lead to the resolution of other major conjectures including Fermat's Last Theorem. A fundamental problem on the representation theory side is the construction of all (irreducible, smooth, complex) representations of certain matrix groups, called p-adic groups. Despite much progress in the past 40 years, we still know surprisingly little about these representations in the general setting. My first main objective is the construction of all (supercuspidal) representations in full generality. This will form the foundation for the future of the representation theory of p-adic groups and have a plethora of applications also beyond this area. Solving this problem will involve tackling all the complications that arise in the non-tame case compared to the tame case. I will then demonstrate the power of this result beyond the representation theory of p-adic groups by making significant contributions to the - global Langlands program. This will be achieved by constructing congruences between automorphic forms based on the existence of enough suitable (omni-)supercuspidal types for p-adic groups. - relative Langlands program. I will prove finite multiplicity of the representations occurring in the space of function on a spherical variety by combining my results about the shape of representations with properties of the moment map. Finally, I will use my insights to advance the explicit local Langlands correspondence by proving that the most-general construction to date, which treats non-singular representations, satisfies all required properties and suggesting a correspondence beyond non-singular representations.

Mots-clés : p adic groups,reductive groups,supercuspidal representations,bushnell  kutzko types,langlands correspondence,automorphic forms,spherical varieties
Projet ERC : Disasters (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1287755.0 €

My proposal consists of two strands linked by a common theme--namely a concern for the impact of disasters, in financial markets and more generally--and by a shared methodology. In the first of these strands, I propose to develop ways of using observable asset price data to infer the beliefs of market participants about various quantities that are central to financial economics, including (i) the equity premium; (ii) the forward-looking autocorrelation of the market (i.e., time-series momentum); (iii) the risk premia associated with individual stocks; (iv) the correlation between stocks; and (v) measures of asymmetric risk, such as the forward-looking probability of a significant downward jump in the stock market over some prescribed time period. This work will exploit theoretical techniques that I have developed in previous research, and that allow for the possibility of jumps and disasters in financial markets. I will therefore be able to avoid the unpalatable assumption—which is made, implicitly or explicitly, in much of the finance literature—that uncertainty is driven by conditionally Normally distributed shocks (or, in continuous time, by Brownian motions). The importance of doing so is underscored by the turmoil in financial markets over the last few years. These techniques will also be applied in the second strand of my proposal, which focuses on issues related to catastrophes more generally, including for example climate change; highly contagious viruses on the scale of the influenza pandemic of 1918; or nuclear or bio-terrorism. This project will be joint with Professor Robert S. Pindyck of MIT. The goal is to provide a framework within which policymakers, faced with multiple different types of potential catastrophe, can determine how society’s limited resources should best be used to alleviate the associated risks.

Mots-clés : equity premium,jumps in financial markets,cumulants,options,natural disasters
Projet ERC : PAPAstudy (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université Paris Cité — Pays : France — Rôle : PI
Acronyme de l'entité : UP Cité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1479260.0 €

My research project is focused on the biology of the podocyte during chronic kidney disease progression, one of the major public health challenges of the 21st Century. The podocyte is a highly specialized cell with foot processes expansion that function as vasculature-supporting cells, producing basement membrane components and a number of vascular growth factors. These cells play an essential role in renal physiology but their unique localization, as the primary filter, exposes them to many stresses in pathological conditions. In fact these cells are the direct target of many diseases such as diabetes or HIV. The molecular events and structural changes in podocyte during adaptation to nephron reduction are not well-characterized and efficient therapeutics dramatically lacking. In order to achieve the ultimate goal of improving care provided to patients suffering from renal failure, the dissection of the molecular pathways involved in podocyte adaptation and deterioration processes is mandatory. This project will combine complementary in vivo and in vitro approaches, experimental models of chronic kidney disease on genetically modified mice, as well as the use of a very innovative and new technology of bioengineering to explore the molecular and structural changes of the podocytes during kidney diseases. This work will be centralized on AKT2 and its partners, as we previously demonstrated its major role in podocyte adaptation to nephron reduction, but also on new players using unbiased approaches. In parallel and consistently with my previous works, we will systematically extend our findings to human through our unique Renal Biobank of Necker Hospital (Paris). The accomplishment of this project may lead to the discovery of novel therapeutic targets and strategies to slow down the progression of kidney disease.

Mots-clés : podocyte,nephron reduction,collapsing glomerulopathy
Projet ERC : 3D2DPrint (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Trinity College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : TCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499942.0 €

My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices. Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies. 3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.

Mots-clés : additive manufacturing,3d printing,nanomaterials,2 dimensional nanosheets,supercapacitors,batteries,hybrids
Projet ERC : NMDADYN (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

NMDA receptors (NMDARs) have long fascinated neuroscientists with their distinct biophysical properties and critical roles in neuronal communication and plasticity. Recent studies have revealed that these glutamate-gated ion channels are more complex than initially thought, undergoing tight subunit-specific regulation by an array of endogenous modulators and existing as multiple subtypes, each with its own anatomical, functional and signaling properties. Such complexity raises key questions regarding the conformational changes that this multi-domain receptor undergoes, the physiological relevance of its subunit plurality and the microenvironment’s impact on receptor and circuit function. To address these challenges, this project uses innovative strategies at the crossroads of protein engineering, biological chemistry and neuroscience to achieve a molecular level control of NMDARs that is subunit-specific, reversible and usable both in vitro and in vivo. Using a bottom-up approach, it contains four aims covering molecular, cellular and behavioral levels. The first two investigate NMDAR structural mechanisms and exploit this knowledge to develop new optochemical receptor tools. The next two address physiological questions using these tools as well as original biosensors and novel mouse lines. Aim 1: Characterize NMDAR conformational dynamics and allosteric transitions Aim 2: Engineer a family of light-controlled NMDARs (‘Opto-allostery’) Aim 3: Understand the role of specific NMDAR populations in neuronal functions Aim 4: Explore the receptor’s synaptic microenvironment in normal and disease states This multi-scale project creates and implements the spatially and temporally sensitive tools required to break the barriers to our understanding of NMDAR diversity and modulation. The results will provide fundamental insights into the intricate workings of an essential class of brain receptors and further our comprehension of neuronal excitatory transmission and pathology.

Mots-clés : glutamate receptors,synapses,neurotransmission,optopharmacology,protein engineering
Projet ERC : ULT-NEMS (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1966375.04 €

Nano-electro-mechanical devices (NEMS) are extremely small objects that can be actuated and detected by electric means. They are in the first place transducers that can be used as probes for forces down to the molecular level. Top-down fabricated NEMS using conventional microelectronics techniques are simple devices that intimately link mechanical and electrical degrees of freedom. As such, they can be viewed as model systems from basic (linear) harmonic motion up to complex nonlinear dynamics. The most intriguing experimental situation is attained when the devices are cold enough to behave according to the laws of quantum mechanics, instead of classical physics. This leads to a unique approach of the classical-to-quantum crossover with truly macroscopic position-states. Complementarily, at low temperatures the forces sensed by the NEMS arise from materials themselves cold enough to exhibit exotic quantum properties, originating either in the devices’ constitutive amorphous materials and their intrinsic elusive Tunneling Systems, or from their interaction with a sophisticated fluid like superfluid 3He. I propose unique research linking ultra-low temperature physics and nano-mechanics, building on my knowledge of both fields and my experience in superconducting quantum circuits. The research has two identified axes, which aim at pushing both the “sensor” and “model system” aspects of NEMS down to their quantum retrenchments. Macroscopic quantum position-states can be engineered with a hybrid quantum circuit arrangement (a combination of NEMS, microwaves and quantum bit), while topological states of confined superfluid 3He with their elementary excitations can be mechanically probed by dedicated NEMS (measuring friction). The scientific impact of this research is extremely wide, tackling fundamental questions like: what/where is the boundary between quantum and classical worlds, and do Majorana particles (potentially obtained in topological 3He) exist at all?

Mots-clés : low temperature physics,quantum fluids and solids,quantum mechanics and decoherence,non linear dynamics
Projet ERC : NanoBeam (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Kiel University — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : CAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1337095.0 €

NanoBeam will develop new directions in electron microscopy, materials, and optical sciences to control and characterize the ultrafast responses of polaritons and electronic states in materials. This will be achieved by (i) a ubiquitous control of slow and fast electron wave packets and (ii) realization of fully coherent light sources using shaped electron wave packets interacting with nanostructures. Quantum coherent control traditionally employs a sequence of optical pulses to direct the response of condensed matter systems towards a desired state, as a tool for novel quantum technologies. This control system has been only recently implemented in electron microscopes, by combining lasers and photoemission electron guns. However, this field is still it its infancy because it does not provide us with important aspects of the sample response such as spectral phase and time-energy evolution of electronic states in samples, which happens at the attosecond time scale. NanoBeam aims at quantum coherent control within electron microscopes by triggering both electron wave packets and their mechanisms of radiation, using carefully engineered nanostructures. This innovative and unconventional control system is to be achieved by an unprecedented combination of theory and experiment. On the theoretical side, I plan to develop a Maxwell-Schrödinger self-consistent numerical toolbox, to fully understand the interaction of electron wave packets with light and nanostructures beyond the routinely used adiabatic approximations, but also to utilize our expertise in theoretical modelling to propose novel methodologies for coherent control and shaping of the electron beams. On the experimental side, I intend to develop a novel spectral interferometry technique with the ability to retrieve and control the spectral phase in a scanning electron microscope to overcome the challenges in meeting both nanometer spatial and attosecond time resolution.

Mots-clés : electron photon interactions,quantum coherent control,spectral interferometry
Projet ERC : SmartSpacer (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149909.68 €

Nanofiltration (NF) and reverse osmosis (RO) membranes are widely and increasingly used for water treatment process. The efficiency of NF and RO processes is however adversely affected by biofouling. Environmental stimuli can trigger selfcleaning mechanisms of natural surfaces. Consequently there is an increasing interest in developing smart or stimuli responsive polymers as coatings to prevent biofouling. However, external chemical/physical stimuli must be selectively applied to the smart polymers to induce the cleaning mechanism; this procedure limits their applicability at industrial scale. The unique idea of this Proof of Concepts is to develop smart polymeric surfaces that, triggered by chemical (enzymatic) stimuli induced by biofouling, will exploit the self-cleaning mechanism. This concept is expected to dramatically reduce the operating costs of NF and reverse osmosis RO processes. Bio-stimulated smart polymers surfaces will be incorporated into NF/RO feed spacers which are integral to the spiral wound configuration used in full scale membrane treatment plants. The commercialisation route of the product will be through the patent protection and the licensing of the technology with a view to rapid commercialisation.

Mots-clés : water,biofouling,reverse osmosis,nanofiltration,fouling,polymer