ERC FUNDED PROJECTS

What is responsible for the emergence of homochirality, the almost exclusive use of one enantiomer over its mirror image? And what led to the evolution of life’s homochiral biopolymers, DNA/RNA, proteins and lipids, where all the constituent monomers exhibit the same handedness? Based on in-situ observations and laboratory studies, we propose that this handedness occurs when chiral biomolecules are synthesized asymmetrically through interaction with circularly polarized photons in interstellar space. The ultimate goal of this project will be to demonstrate how the diverse set of heterogeneous enantioenriched molecules, available from meteoritic impact, assembles into homochiral pre-biopolymers, by simulating the evolutionary stages on early Earth. My recent research has shown that the central chiral unit of RNA, ribose, forms readily under simulated comet conditions and this has provided valuable new insights into the accessibility of precursors of genetic material in interstellar environments. The significance of this project arises due to the current lack of experimental demonstration that amino acids, sugars and lipids can simultaneously and asymmetrically be synthesized by a universal physical selection process. A synergistic methodology will be developed to build a unified theory for the origin of all chiral biological building blocks and their assembly into homochiral supramolecular entities. For the first time, advanced analyses of astrophysical-relevant samples, asymmetric photochemistry triggered by circularly polarized synchrotron and laser sources, and chiral amplification due to polymerization processes will be combined. Intermediates and autocatalytic reaction kinetics will be monitored and supported by quantum calculations to understand the underlying processes. A unified theory on the asymmetric formation and self-assembly of life’s biopolymers is groundbreaking and will impact the whole conceptual foundation of the origin of life.

1 500 000 €

Start date: 2019-04-01, End date: 2024-03-31

The key ideas motivating this project are that: 1) precise control of the properties of porous systems can be obtained by exploiting bacteria and their fantastic abilities; 2) conversely, porous media (large surface to volume ratios, complex structures) could be a major part of bacterial synthetic biology, as a scaffold for growing large quantities of microorganisms in controlled bioreactors. The main scientific obstacle to precise control of such processes is the lack of understanding of biophysical mechanisms in complex porous structures, even in the case of single-strain biofilms. The central hypothesis of this project is that a better fundamental understanding of biofilm biomechanics and physical ecology will yield a novel theoretical basis for engineering and control. The first scientific objective is thus to gain insight into how fluid flow, transport phenomena and biofilms interact within connected multiscale heterogeneous structures - a major scientific challenge with wide-ranging implications. To this end, we will combine microfluidic and 3D printed micro-bioreactor experiments; fluorescence and X-ray imaging; high performance computing blending CFD, individual-based models and pore network approaches. The second scientific objective is to create the primary building blocks toward a control theory of bacteria in porous media and innovative designs of microbial bioreactors. Building upon the previous objective, we first aim to extract from the complexity of biological responses the most universal engineering principles applying to such systems. We will then design a novel porous micro-bioreactor to demonstrate how the permeability and solute residence times can be controlled in a dynamic, reversible and stable way - an initial step toward controlling reaction rates. We envision that this will unlock a new generation of biotechnologies and novel bioreactor designs enabling translation from proof-of-concept synthetic microbiology to industrial processes.

1 649 861 €

Start date: 2019-01-01, End date: 2023-12-31

Few geophysical phenomena are as spectacular as tropical cyclones, with their eye surrounded by sharp cloudy eyewalls. There are other types of spatially organised convection (convection refers to overturning of air within which clouds are embedded), in fact organised convection is ubiquitous in the tropics. But it is still poorly understood and poorly represented in convective parameterisations of global climate models, despite its strong societal and climatic impact. It is associated with extreme weather, and with dramatic changes of the large scales, including drying of the atmosphere and increased outgoing longwave radiation to space. The latter can have dramatic consequences on tropical energetics, and hence on global climate. Thus, convective organisation could be a key missing ingredient in current estimates of climate sensitivity from climate models. CLUSTER will lead to improved fundamental understanding of convective organisation to help guide and improve convective parameterisations. It is closely related to the World Climate Research Programme (WCRP) grand challenge: Clouds, circulation and climate sensitivity. Grand challenges identify areas of emphasis in the coming decade, targeting specific barriers preventing progress in critical areas of climate science. Until recently, progress on this topic was hindered by high numerical cost and lack of fundamental understanding. Advances in computer power combined with new discoveries based on idealised frameworks, theory and observational findings, make this the ideal time to determine the fundamental processes governing convective organisation in nature. Using a synergy of theory, high-resolution cloud-resolving simulations, and in-situ and satellite observations, CLUSTER will specifically target two feedbacks recently identified as being essential to convective aggregation, and assess their impact on tropical cyclones, large-scale properties including precipitation extremes, and energetics of the tropics.

1 078 021 €

Start date: 2019-06-01, End date: 2024-05-31

Chemical samples often come as solution mixtures. While advanced analytical methods exist for samples at equilibrium, the information on components and their interactions that may be accessed for the frequent and important case of out-of-equilibrium mixtures is much more limited. The DINAMIX project will tackle this challenge and provide detailed, molecular-level information on out-of-equilibrium mixtures. The proposed concept relies on diffusion nuclear magnetic resonance (NMR) spectroscopy, a powerful method that separates the spectra of mixtures’ components and identifies interactions, in correlation with structural insight provided by NMR observables. While classic experiments require several minutes, spatial encoding (SPEN) in principle makes it possible to acquire data orders of magnitude faster, in less than a second. The PI has recently demonstrated that SPEN diffusion NMR is a general concept, with the potential to provide real-time information on out-of-equilibrium mixtures. These include a vast range of systems undergoing chemical change, as well as the important class of “hyperpolarised” solution mixtures generated by dissolution dynamic nuclear polarisation (D-DNP). D-DNP indeed provides dramatic NMR sensitivity enhancements of up to 4 orders of magnitude, which however last only for a short time in solution. In the DINAMIX project, we will develop i/ novel robust and accurate real-time diffusion NMR methods, ii/ advanced algorithms for data processing and analysis, iii/ protocols for sensitive component identification. We will exploit the resulting methodology for mechanistic investigations into catalytic organic and enzymatic reactions. The real-time diffusion NMR analysis of systems that are out-of-chemical equilibrium, far-from-spin-equilibrium or both will provide transformative insight on mixtures, with applications in chemical synthesis, supramolecular and polymer science, structural biology, and microstructural studies in materials and in vivo.

1 499 307 €

Start date: 2019-02-01, End date: 2024-01-31

Unravelling how tectonics, climate and surface processes act and interact to shape the Earth’s surface is one of the most challenging unresolved issue in Earth Sciences. The foundations of modern quantitative geomorphology have been built within the paradigm of steady-state landscapes responding to slow changes in climatic or tectonic conditions, mainly rainfall or uplift rate. Yet, recent results demonstrate that landscapes are rhythmed by (potentially extreme) storms and earthquakes. These perturbations catalyse geomorphological processes by triggering numerous landslides and lead to a prolonged and transient evolution of the landscape that dominate records of modern erosion. The FEASIBLe project therefore calls for a complete re-assessment of the role of short-term climatic and tectonic perturbations in shaping mountain landscapes and for a paradigm shift from steady-state to constantly perturbed landscapes. My ambition is to push forward our understanding of the short- to long-term dynamics of perturbed landscapes and in turn to unlock our ability to read landscapes in terms of earthquake and storm activity. To succeed in this endeavour, the FEASIBLe project will rely on the development of a new generation of landscape evolution model and of novel approaches to intimately monitor landscape heterogeneities and evolution in Taiwan, New-Zealand and Himalayas at high-resolution. The first work packages (WP1-2) will combine field-data analysis and numerical modelling to investigate landslide triggering and the post-perturbation sediment evacuation and landscape dynamics. I will then blend these elementary processes with a statistical description of climatic and tectonic perturbations in a new generation of landscape evolution model (WP3). This new model will be then applied to diagnose the geomorphological signature of fault “seismogenic” rheology (WP4) and to explore the role of post-glacial hot-moments of landscape dynamics on Quaternary landscape evolution (WP5).

1 498 829 €

Start date: 2019-06-01, End date: 2024-05-31

The last seismic sequence in Italy, responsible for 298 fatalities and important economic loss, remind us how urgent it is to improve our knowledge about earthquake physics to advance earthquake forecasting. While direct observations during laboratory earthquakes permit us to derive exhaustive physical models describing the behaviour of rocks and to forecast incoming lab-earthquakes, the complex physics governing the nucleation of earthquakes remain poorly understood in real Earth, and so does our ability to forecast earthquakes. I posit that this ‘ignorance’ emerges from our limited ability to unravel information about fault physics from geophysical data.The objective of this proposal is to introduce a new and integrated methodology to monitor the spatiotemporal evolution of elastic properties on real faults using seismological and geodetic data. We will apply machine learning and covariance matrix factorization for improved earthquake detection, and to discover ‘anomalous’ seismological signals, which will reveal unknown physical processes on faults. These novel observations will be integrated with time dependent measurements of rheology and deformation, obtained from cutting-edge techniques applied to continuous seismological and geodetic data. Our integrated monitoring approach will be applied to study how faults respond to known stress perturbations (as Earth tides). In parallel, we will analyse periods preceding significant earthquakes to assess how elastic properties and deformation evolve while a fault is approaching a critical (near rupture) state. Our natural laboratory will be Italy, given its excellent geodetic and seismological instrumentation, deep knowledge about faults geometry and the relevant risk posed by earthquakes. Our research will provide new insights about the complex physics of faults at critical state, necessary to understand how real earthquakes nucleate. This project will also have a major impact on observational earthquake forecast.

1 393 174 €

Start date: 2019-01-01, End date: 2023-12-31

Over the last decades, new discoveries have revealed an ever-increasing diversity of RNA functions, profoundly modifying the conceptual framework of molecular biology. This is the case of micro-RNAs (miRNA), a fascinating class of small non-coding RNA that play essential roles in RNA induced gene silencing and are estimated to target up to 60% of protein-coding genes in humans. RNA functional diversity is often triggered by conformational changes, so capturing the dynamics of these molecules is key to a precise understanding of their function, which in turn is essential to control their activity. Nuclear Magnetic Resonance (NMR) spectroscopy is extremely well suited to investigate dynamical processes. However, the sparsity of measureable NMR data in a RNA sample represents a major bottleneck, preventing so far an accurate description of RNA conformational fluctuations. This project aims to overcome this barrier by developing paramagnetic NMR for RNA. By chemically modifying an RNA, I will introduce paramagnetic tags to strategic positions so as to acquire NMR data from otherwise silent substrate. Adequate computational and analytical models will be developed to decode the experimental data into an atomic-level description of dynamics. These goals require a leap forward with respect to today’s approaches. I propose to achieve this by combining innovative sample preparation strategies and NMR experiments, high magnetic fields, and MD simulations. With these methods, I will enable the determination of the dynamic landscape of let-7, the first miRNA discovered in humans, involved in cell proliferation and differentiation and oncogenesis. This project will yield a broadly applicable method for the structural and dynamic characterization of RNA with unprecedented details. This knowledge will improve our fundamental biochemical and biophysical conception of RNA, opening new avenues for bioengineering and establishing the bases for rational RNA-oriented drug discovery.

1 633 500 €

Start date: 2019-02-01, End date: 2024-01-31

How do earthquakes begin? Answering this question is essential to understand fault mechanics but also to determine our ability to forecast large earthquakes. Although it is well established that some events are preceded by foreshocks, contrasting views have been proposed on the nucleation of earthquakes. Do these foreshocks belong to a cascade of random failures leading to the mainshock? Are they triggered by an aseismic nucleation phase in which the fault slips slowly before accelerating to a dynamic, catastrophic rupture? Will we ever be able to monitor and predict the slow onset of earthquakes or are we doomed to observe random, unpredictable cascades of events? We are currently missing a robust tool for quantitative estimation of the proportion of seismic versus aseismic slip during the rupture initiation, cluttering our attempts at understanding what physical mechanisms control the relationship between foreshocks and the onset of large earthquakes. The current explosion of available near-fault ground-motion observations is an unprecedented opportunity to capture the genesis of earthquakes along active faults. I will develop an entirely new method based a novel data assimilation procedure that will produce probabilistic time-dependent slip models assimilating geodetic, seismic and tsunami datasets. While slow and rapid fault processes are usually studied independently, this unified approach will address the relative contribution of seismic and aseismic deformation. The first step is the development of a novel probabilistic data assimilation method providing reliable uncertainty estimates and combining multiple data types. The second step is a validation of the method and an application to investigate the onset of recent megathrust earthquakes in Chile and Japan. The third step is the extensive, global use of the algorithm to the continuous monitoring of time-dependent slip along active faults providing an automated detector of the nucleation of earthquakes.

1 499 545 €

Start date: 2019-01-01, End date: 2023-12-31

Current methods in organic synthesis only enable reactions at the most reactive bonds or at bonds predisposed by specific directing groups. Consequently, many less reactive bonds, including numerous C-H and C-C bonds, cannot be functionalized, enormously limiting the scope of possible transformations. To overcome these limitations, I propose Reverse&Cat, a revolutionary strategy using a novel method to change the reactivity pattern of molecules. This strategy combines the dynamic equilibrium mediated by the first catalyst and a functionalization reaction catalyzed by the second catalyst. The originality of the transformation stems from exploiting three simultaneous processes: (i) the dynamic exchange of one functional group (FG) for another FG that modulates the reactivity of the substrate; (ii) the functionalization of the temporarily activated bond; and (iii) the restoration of the initial FG. In essence, the processes (i) and (iii) – the components of the dynamic equilibrium – realize the novel concept of the temporary creation of non-inherent reactivity of a substrate. The program is divided in three phases, which will establish the full potential of the strategy. In phase A, I will develop a set of new reactions enabled by the bi-catalytic systems. I will exploit two types of reversible reactions: (1) reversible oxidation of alcohols, which delivers temporarily activated aldehydes/ketones, with the distinct reactivity of their C-H bonds; and (2) reversible retro-hydrofunctionalization of nitriles or their analogues, which delivers temporarily activated alkenes, containing allylic C-H and C=C bonds. In phase B, I will conduct detailed mechanistic studies to gain the mechanistic understanding and enable further rational development. In phase C, I will establish the utility of this new strategy in practical organic synthesis. Overall, the strategy will open a new dimension of reactivity, with prospective applications in production of fine-chemicals and materials.

1 731 250 €

Start date: 2018-11-01, End date: 2023-10-31