ERC FUNDED PROJECTS

The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research. The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation. The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event. Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.

1 489 823 €

Start date: 2017-03-01, End date: 2022-02-28

The fundamental 3D-BioMat project aims at providing a biomineralization model to explain the formation of microscopic calcareous single-crystals produced by living organisms. Although these crystals present a wide variety of shapes, associated to various organic materials, the observation of a nanoscale granular structure common to almost all calcareous crystallizing organisms, associated to an extended crystalline coherence, underlies a generic biomineralization and assembly process. A key to building realistic scenarios of biomineralization is to reveal the crystalline architecture, at the mesoscale, (i. e., over a few granules), which none of the existing nano-characterization tools is able to provide. 3D-BioMat is based on the recognized PI’s expertise in the field of synchrotron coherent x-ray diffraction microscopy. It will extend the PI’s disruptive pioneering microscopy formalism, towards an innovative high-throughput approach able at giving access to the 3D mesoscale image of the crystalline properties (crystal-line coherence, crystal plane tilts and strains) with the required flexibility, nanoscale resolution, and non-invasiveness. This achievement will be used to timely reveal the generics of the mesoscale crystalline structure through the pioneering explorations of a vast variety of crystalline biominerals produced by the famous Pinctada mar-garitifera oyster shell, and thereby build a realistic biomineralization scenario. The inferred biomineralization pathways, including both physico-chemical pathways and biological controls, will ultimately be validated by comparing the mesoscale structures produced by biomimetic samples with the biogenic ones. Beyond deciphering one of the most intriguing questions of material nanosciences, 3D-BioMat may contribute to new climate models, pave the way for new routes in material synthesis and supply answers to the pearl-culture calcification problems.

1 966 429 €

Start date: 2017-03-01, End date: 2022-02-28

In the coming few decades, two major global grand challenges will continue to attract the attention of scientists and engineers in academia and industry: achieving clean water and clean energy. This PoC establishes the development of two prototypes, water oxidation catalyst and water purification filter, by creating inexpensive, abundant and versatile hierarchical structures of inorganic nanomaterials (HSINs). The formation of HSINs has been one of the major obstacles toward achieving a technological progress in various applications. Presently, fabrication of well-defined 3-D structures can be achieved either by photo/electro lithography, assembly, 3D printing or template-mediated methods. Various structures with high quality/yield can be obtained through those techniques, however, these methods suffer from high cost, difficulty of fabrication of free-standing structures, and sometime the throughput is limited. On the other hand, the templated approaches usually are facile, low cost and offer several and complex structures in particular the ones obtained from nature. Our invention is based on forming the HSINs using fossil templates from nature. We propose to harness the naturally designed morphologies of the fossil templates to rationally form hierarchical structures of nanomaterials. These structures have many advantageous, compared to the current state-of-the-art catalyst and filter, for example high surface area, high porosity, confined space (nano-reactor) and divers functionalities obtained by controlling the chemical composition of the inorganic material shell. Since these properties are important for achieving high performance, we propose HSINs as next generation water oxidation electrocatalyst and water purification filter.

150 000 €

Start date: 2017-03-01, End date: 2018-08-31

Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy

2 149 228 €

Start date: 2017-12-01, End date: 2022-11-30

"Antibodies are among the most widely monitored class of diagnostic biomarkers. Immunoassays market now covers about 1/3 of the global market of in-vitro diagnostics (about $50 billion). However, current methods for the detection of diagnostic antibodies are either qualitative or require cumbersome, resource-intensive laboratory procedures that need hours to provide clinicians with diagnostic information. A new method for fast and low-cost detection of antibodies will have a strong economic impact in the market of in-vitro diagnostics and Immunoassays. During our ERC Starting Grant project ""Nature Nanodevices"" we have developed a novel diagnostic technology for the detection of clinically relevant antibodies in serum and other body fluids. The platform (here named Ab-switch) supports the fluorescent detection of diagnostic antibodies (for example, HIV diagnostic antibodies) in a rapid (<3 minutes), single-step and low-cost fashion. The goal of this Proof of Concept project is to bring our promising platform to the proof of diagnostic market and exploit its innovative features for commercial purposes. We will focus our initial efforts in the development of rapid kits for the detection of antibodies diagnostic of HIV. We will 1) Fully characterize the Ab-switch product in terms of analytical performances (i.e. sensitivity, specificity, stability etc.) with direct comparison with other commercial kits; 2) Prepare a Manufacturing Plan for producing/testing the Ab-switch; 3) Establish an IP strategy for patent filing and maintenance; 4) Determine a business and commercialization planning."

150 000 €

Start date: 2017-02-01, End date: 2018-07-31

In tissues, cells have their physical space constrained by neighbouring cells and extracellular matrix. In the PROMICO ERC project, our team proposed to specifically address the effect of physical confinement on normal and cancer cells that are dividing and migrating, using new pathophysiologically relevant in vitro approaches based on innovative micro-fabrication techniques. One of the devices we developed was meant to quantitatively control two key parameters of the cell environment: its geometry and its surface chemical properties. The main technical breakthrough was achieved using micro-fabricated elastomeric structures bound to a hard substrate (Le Berre Integrative Biology, 2012). The method led to important fundamental discoveries in cell biology (Lancaster Dev Cell 2013, Le Berre PRL 2013, Liu Cell 2015, Raab Science 2016). In part based on our findings, the notion that confinement is a crucial parameter for cell physiology has spread through the cell biology. Based on this, our idea is that cell confinement could be used as a powerfull cell conditioning technology, to change the cell state and offer new opportunities for fundamental research in cell biology, but also in cell therapies and drug screening. However, our current method to confine cells is not adapted to large scale cell conditioning applications, because the throughput and reliability of the device is still too low and because the recovery of cells after confinement remain poorly controlled. It is thus now timely to develop a robust and versatile cell confiner adapted to use in any cell biology lab, in academy and in industry, with no prior experience in micro-fabrication. Achieving this goal involves a complete change of technology compared to the ‘homemade’ PDMS device we have been using so far. We will also perform proofs of concept of its use for its application in cell based therapies, such as cancer immunotherapy, by testing the possibility to mechanically activate dendritic cells.

150 000 €

Start date: 2017-06-01, End date: 2018-11-30

Robot-assisted and minimally invasive medical procedures are impacting medical care by increasing accuracy, reducing cost, and minimizing patient discomfort and recovery times after interventions. Developers of commercial robotic surgical systems and medical device manufacturers look for realistic phantoms that can be used in place of animal experiments or cadavers to test procedures and to train medical personnel. Existing phantoms are either made from hard materials, or they lack anatomical detail, and they are mainly passive and thus unrealistic. Here, we use recently developed fabrication know-how and expertise within our ERC-funded research to develop the first active artificial urinary tract model that includes a kidney, a bladder, and a prostate. Rapid prototyping is combined with a fabrication step that we have developed to permit the incorporation of active elements, such as a peristaltic system and fluidic valves in the phantom. We have developed smart material composites that reproduce the mechanical and haptic properties, and that give ultrasound contrast indistinguishable from real organs, while permitting anatomical details to be reproduced with a mean error of as little as 500 microns. Feedback from a major medical device company indicates that ours is a unique phantom with unprecedented accuracy for which there is a market. Within this POC grant we want to develop a complete prototype, and to demonstrate a series of medical interventions on the phantom, including endoscopic diagnostic procedures (cystoscopy and ureterorenoscopy) and endoscopic treatment procedures (laser lithotripsy). The grant will allow us to protect our know-how, identify further markets, and develop a commercialization strategy. Overall, this project will generate the first active phantom system that permits the testing of surgical instruments and procedures, with a sizeable market potential.

150 000 €

Start date: 2017-03-01, End date: 2018-08-31

The understanding of spatial, social and dynamical organization of large numbers of agents is presently a fundamental issue in modern science. ADORA focuses on problems motivated by biology because, more than anywhere else, access to precise and many data has opened the route to novel and complex biomathematical models. The problems we address are written in terms of nonlinear partial differential equations. The flux-limited Keller-Segel system, the integrate-and-fire Fokker-Planck equation, kinetic equations with internal state, nonlocal parabolic equations and constrained Hamilton-Jacobi equations are among examples of the equations under investigation. The role of mathematics is not only to understand the analytical structure of these new problems, but it is also to explain the qualitative behavior of solutions and to quantify their properties. The challenge arises here because these goals should be achieved through a hierarchy of scales. Indeed, the problems under consideration share the common feature that the large scale behavior cannot be understood precisely without access to a hierarchy of finer scales, down to the individual behavior and sometimes its molecular determinants. Major difficulties arise because the numerous scales present in these equations have to be discovered and singularities appear in the asymptotic process which yields deep compactness obstructions. Our vision is that the complexity inherent to models of biology can be enlightened by mathematical analysis and a classification of the possible asymptotic regimes. However an enormous effort is needed to uncover the equations intimate mathematical structures, and bring them at the level of conceptual understanding they deserve being given the applications motivating these questions which range from medical science or neuroscience to cell biology.

2 192 500 €

Start date: 2017-09-01, End date: 2022-08-31

Parameterized mathematical models have been central to the understanding and design of communication, networking, and radar systems. However, they often lack the ability to model intricate interactions innate in complex systems. On the other hand, data-driven approaches do not need explicit mathematical models for data generation and have a wider applicability at the cost of flexibility. These approaches need labelled data, representing all the facets of the system interaction with the environment. With the aforementioned systems becoming increasingly complex with intricate interactions and operating in dynamic environments, the number of system configurations can be rather large leading to paucity of labelled data. Thus there are emerging networks of systems of critical importance whose cognition is not effectively covered by traditional approaches. AGNOSTIC uses the process of exploration through system probing and exploitation of observed data in an iterative manner drawing upon traditional model-based approaches and data-driven discriminative learning to enhance functionality, performance, and robustness through the notion of active cognition. AGNOSTIC clearly departs from a passive assimilation of data and aims to formalize the exploitation/exploration framework in dynamic environments. The development of this framework in three applications areas is central to AGNOSTIC. The project aims to provide active cognition in radar to learn the environment and other active systems to ensure situational awareness and coexistence; to apply active probing in radio access networks to infer network behaviour towards spectrum sharing and self-configuration; and to learn and adapt to user demand for content distribution in caching networks, drastically improving network efficiency. Although these cognitive systems interact with the environment in very different ways, sufficient abstraction allows cross-fertilization of insights and approaches motivating their joint treatment.

2 499 595 €

Start date: 2017-10-01, End date: 2022-09-30