ERC FUNDED PROJECTS

Aeroelastic instabilities are at the origin of large deformations of structures and are limiting the capacities of products in various industrial branches such as aeronautics, marine industry, or wind electricity production. If suppressing aeroelastic instabilities is an ultimate goal, a paradigm shift in the technological development is to take advantage of these instabilities to achieve others objectives, as reducing the drag of these flexible structures. The ground-breaking challenges addressed in this project are to design fundamentally new theoretical methodologies for (i) describing mathematically aeroelastic instabilities, (ii) suppressing them and (iii) using them to reduce mean drag of structures at a low energetic cost. To that aim, two types of aeroelastic phenomena will be specifically studied: the flutter, which arises as a result of an unstable coupling instability between two stable dynamics, that of the structures and that the flow, and vortex-induced vibrations which appear when the fluid dynamics is unstable. An aeroelastic global stability analysis will be first developed and applied to problems of increasing complexity, starting from two-dimensional free-vibrating rigid structures and progressing towards three-dimensional free-deforming elastic structures. The control of these aeroelastic instabilities will be then addressed with two different objectives: their suppression or their use for flow control. A theoretical passive control methodology will be established for suppressing linear aeroelastic instabilities, and extended to high Reynolds number flows and experimental configurations. New perturbation methods for solving strongly nonlinear problems and adjoint-based control algorithm will allow to use these aeroelastic instabilities for drag reduction. This project will allow innovative control solutions to emerge, not only in flutter or vortex-induced vibrations problems, but also in a much broader class of fluid-structure problems.

1 377 290 €

Start date: 2015-07-01, End date: 2020-06-30

Rupture of Aortic Aneurysms (AA), which kills more than 30 000 persons every year in Europe and the USA, is a complex phenomenon that occurs when the wall stress exceeds the local strength of the aorta due to degraded properties of the tissue. The state of the art in AA biomechanics and mechanobiology reveals that major scientific challenges still have to be addressed to permit patient-specific computational predictions of AA rupture and enable localized repair of the structure with targeted pharmacologic treatment. A first challenge relates to ensuring an objective prediction of localized mechanisms preceding rupture. A second challenge relates to modelling the patient-specific evolutions of material properties leading to the localized mechanisms preceding rupture. Addressing these challenges is the aim of the BIOLOCHANICS proposal. We will take into account internal length-scales controlling localization mechanisms preceding AA rupture by implementing an enriched, also named nonlocal, continuum damage theory in the computational models of AA biomechanics and mechanobiology. We will also develop very advanced experiments, based on full-field optical measurements, aimed at characterizing localization mechanisms occurring in aortic tissues and at identifying local distributions of material properties at different stages of AA progression. A first in vivo application will be performed on genetic and pharmacological models of mice and rat AA. Eventually, a retrospective clinical study involving more than 100 patients at the Saint-Etienne University hospital will permit calibrating estimations of AA rupture risk thanks to our novel approaches and infuse them into future clinical practice. Through the achievements of BIOLOCHANICS, nonlocal mechanics will be possibly extended to other soft tissues for applications in orthopaedics, oncology, sport biomechanics, interventional surgery, human safety, cell biology, etc.

1 999 396 €

Start date: 2015-05-01, End date: 2020-04-30

Cellular respiration provides energy to power essential processes of life. Respiratory complexes are macromolecular batteries coupling electron flow through a wire of metal clusters and cofactors with proton transfer across the inner membrane of mitochondria and bacteria. Waste products of these cellular factories are reactive oxygen species causing ageing and diseases. Assembly and maturation mechanisms of respiratory complexes remain enigmatic because of their membrane location, multisubunit composition and cofactor insertion. E. coli Complex I, one of the largest membrane proteins, composed of 14 conserved subunits with 9 Fe/S clusters and a flavin, is a minimal model for its 45-subunit human homologue. When proton pumping by respiratory complexes is affected, bacteria become resistant to antibiotics requiring proton gradient for uptake. Based on the latest genetic data, we realize that the huge E. coli macromolecular cage, the structure of which we recently solved by cryo-electron microscopy (cryoEM), in conjunction with a novel protein cofactor, is a specific chaperone for Fe/S cluster biogenesis and assembly of respiratory complexes. This integrated multidisciplinary project combines cryoEM and other structural, biophysical and spectroscopic techniques, to uncover the functional mechanism of this emerging chaperone. The structural plasticity of the chaperone fuelled by ATP hydrolysis, and its interaction with Fe/S cluster biogenesis systems and the main respiratory complexes as a function of stresses, will be scrutinized to gain quasiatomic insights into the way the chaperone operates on its substrates. A novel technology for synergetic in situ investigation of protein complexes in the bacterial cytoplasm by optical imaging, state-of-the-art cryogenic correlative light and electron microscopy, and subtomogram analysis, will be developed and used to obtain snapshots of the chaperone-substrate interactions in the cellular context.

1 999 956 €

Start date: 2015-10-01, End date: 2020-09-30

Corneal blindness resulting from disease, physical injury or chemical burns affects millions worldwide and has a considerable economic and social impact on the lives of people across Europe. In many cases corneal transplants can restore vision however the shortage of donor corneas suitable for transplantation has necessitated the development of alternative treatments. The aim of this project is to develop a new approach to corneal tissue regeneration. Previous approaches at engineering corneal tissue have required access to donor cells and lengthy culture periods in an attempt to grow tissue in vitro prior to implantation with only limited success and at great expense. Our approach will differ fundamentally from these in that we will design artificial corneal scaffolds that do not require donated cells or in vitro culture but instead will recruit the patient’s own cells to regenerate the cornea post-implantation. These biomaterial scaffolds will incorporate specific chemical and physical cues with the deliberate aim of attracting cells and inducing tissue formation. Studies will be undertaken to examine how different chemical, biochemical, physical and mechanical cues can be used to control the behaviour of corneal epithelial, stromal and endothelial cells. Once the optimal combination of these cues has been determined, this information will be incorporated into the design of the scaffold. Recent advances in manufacturing and material processing technology will enable us to develop scaffolds with organized nanometric architectures and that incorporate controlled growth factor release mechanisms. Techniques such as 3D bio-printing and nanofiber electrospinning will be used to fabricate scaffolds. The ability of the scaffold to attract cells and promote matrix remodelling will be examined by developing an in vitro bioreactor system capable of mimicking the ocular environment and by performing in vivo tests using a live animal model.

1 498 734 €

Start date: 2015-07-01, End date: 2020-06-30