ERC FUNDED PROJECTS

By 2040, all major sectors of the European economy will be deeply digitalized. By then, the EU aims at reducing greenhouse gas emissions by 60% with respect to 1990 levels. Digitalization will affect decarbonization efforts because of its impacts on energy demand, employment, competitiveness, trade patterns and its distributional, behavioural and ethical implications. Yet, the policy debates around these two transformations are largely disjoint. The aim of the 2D4D project is ensure that the digital revolution acts as an enabler – and not as a barrier – for decarbonization. The project quantifies the decarbonization implications of three disruptive digitalization technologies in hard-to-decarbonize sectors: (1) Additive Manufacturing in industry, (2) Mobility-as-a-Service in transportation, and (3) Artificial Intelligence in buildings. The first objective of 2D4D is to generate a one-of-a-kind data collection to investigate the technical and socio-economic dynamics of these technologies, and how they may affect decarbonization narratives and scenarios. This will be achieved through several data collection methods, including desk research, surveys and expert elicitations. The second objective of 2D4D is to include digitalization dynamics in decarbonization narratives and pathways. On the one hand, this entails enhancing decarbonization narratives (specifically, the Shared Socio-economic Pathways) to describe digitalization dynamics. On the other hand, it requires improving the representation of sector-specific digitalization dynamics in Integrated Assessment Models, one of the main tools available to generate decarbonization pathways. The third objective of 2D4D is to identify no-regret, robust policy portfolios. These will be designed to ensure that digitalization unfolds in an inclusive, climate-beneficial way, and that decarbonization policies capitalize on digital technologies to support the energy transition.

1 498 375 €

Start date: 2020-10-01, End date: 2025-09-30

This project will contribute toward a better understanding of inequality and its macroeconomic implications. We will study inequality and its dynamics along three dimensions: Consumption, Income and Wealth, “3D Inequality.” With novel microdata we can measure the entirety of the economy down to the single household along the 3 dimensions. In macroeconomics, much theoretical progress has been made in understanding when distributions matter for aggregates. Newer heterogeneous agent models deliver strikingly different implications for monetary and fiscal policies than what the traditional representative agent models do, and also allow us to study the distributional implications of different policies across households. In principle, this class of models can incorporate the potentially rich interactions between inequality and the macroeconomy: on the one hand, inequality shapes macroeconomic aggregates; on the other hand, macroeconomic shocks and policies affect inequality. However, absent precise micro-level facts it is difficult to establish which of the potential mechanisms highlighted by these models are the most important in reality. Our empirical efforts will be disciplined by these recent developments in modelling macroeconomic phenomena with microeconomic heterogeneity. Our overarching motivation is to quantify the type of micro heterogeneity that matters for macroeconomic theory and thereby inform the development of current and future macroeconomic models. The novel insights we aim to provide could lead to substantial improvements in both fiscal and monetary policy tools. Furthermore, a better understanding of the forces behind growing inequality will inform the current debate on this issue and provide important lessons to policy makers who see economic inequality as a problem in itself.

1 376 875 €

Start date: 2020-05-01, End date: 2025-04-30

Actual implementation of impactful applications for microfluidic devices in a commercial setting has been surprisingly limited so far. The cause can be to a great extent attributed to the main feature of microfluidic devices: their small dimensions. While miniaturized structures are essential in generating key functionalities, they are also ideal nucleation and anchor sites for solid material present in the liquid that flows through the channels, a phenomenon called fouling. This subsequently results in a reduced or loss of functionality and eventually plugging of the entire flow system. The solution to avoiding fouling is measuring the flow in microfluidic devices in 3D, by particle image velocimetry (PIV), either when designing or using them. However, achieving 3D imaging of flows is currently an extremely difficult task due to the amount of work, high costs and lengthy timelines required. Our value proposition in the ERC Proof of Concept project ‘3D-PIV’ is a table-top device able to efficiently analyse the velocimetry of particles in 3D, offering an unprecedented level of detail of the fluid motion through micron-sized channels/inlets/outlets, opening new possibilities in microfluidics design and validation with significant impact on multiple applications. One of the killer applications we envision, and our focus in this ERC Proof of Concept project, is in the pharmaceutical and chemical industries, for the manufacturing of drugs or chemical components, to enable, adjust or improve their separation. In this project we will focus on building a strong business case for our 3D-PIV technology through prototyping, optimizing software, market analysis and business development.

150 000 €

Start date: 2020-01-01, End date: 2021-06-30

Predicting clinical response to novel and existing anticancer drugs remains a major hurdle for successful cancer treatment. Studies indicate that the tumor ecosystem, resembling an organ-like structure, can limit the predictive power of current therapies that were evaluated solely on tumor cells. The interactions of tumor cells with their adjacent microenvironment are required to promote tumor progression and metastasis, determining drug responsiveness. Such interactions do not form in standard research techniques, where cancer cells grow on 2D plastic dishes. Hence, there is a need to develop new cancer models that better mimic the physio-pathological conditions of tumors. Here, we create 3D-bioprinted tumor models based on a library of hydrogels we developed as scaffold for different tumor types, designed according to the mechanical properties of the tissue of origin. As PoC, we bioprinted a vascularized 3D brain tumor model from brain tumor cells co-cultured with stromal cells and mixed with our hydrogels, that resemble the biophysics of the tumor and its microenvironment. Our patient-derived models consist of cells from a biopsy, constructed according to CT/MRI scans, and include functional vessels allowing for patients' serum to flow when connected to a pump. These models will facilitate reproducible, reliable and rapid results, determining which treatment suits best the specific patient's tumor. Taken together, this 3D-printed model could be the basis for potentially replacing cell and animal models. We predict that this powerful platform will be used in translational research for preclinical evaluation of new therapies and for clinical drug screening, which will save critical time, reduce toxicity and significantly decrease costs generating a major societal benefit. Our platform offers a highly attractive business case, as pharmaceutical and biotech companies heavily invest in preclinical predictive tools for novel personalized drug screening strategies.

150 000 €

Start date: 2019-09-01, End date: 2021-08-31

"Bridging the fields of Computer Animation and Computational Fabrication, this proposal will establish the foundations for algorithmic design of physical structures that can generate lifelike movements. Driven by embedded actuators, these types of structures will enable an abundance of possibilities for a wide array of real-world technologies: animatronic characters whose organic motions will enhance their ability to awe, entertain and educate; soft robotic creatures that are both skilled and safe to be around; patient-specific prosthetics and wearable devices that match the soft touch of the human body, etc. Recent advances in additive manufacturing (AM) technologies are particularly exciting in this context, as they allow us to create designs of unparalleled geometric complexity using a constantly expanding range of materials. And if past developments are an indication, within the next decade we will be able to fabricate physical structures that approach, at least at the macro scale, the functional sophistication of their biological counterparts. However, while this unprecedented capability enables fascinating opportunities, it also leads to an explosion in the dimensionality of the space that must be explored during the design process. As AM technologies keep evolving, the gap between ""what we can produce"" and ""what we can design"" is therefore rapidly growing. To effectively leverage the extraordinary design possibilities enabled by AM, 3DPBio will develop the computational and mathematical foundations required to study a fundamental scientific question: how are physical deformations, mechanical movements and overall functional capabilities governed by geometric shape features, material compositions and the design of compliant actuation systems? By enabling computers to reason about this question, our work will establish new ways to algorithmically create digital designs that can be turned into mechanical lifeforms at the push of a button."

2 000 000 €

Start date: 2020-02-01, End date: 2025-01-31

Understanding how the brain processes information is one of the unsolved grand challenges in science. Moreover, neurological disorders, which disrupt information processing, have an enormous societal and economic impact. Studying information processing in the brain requires measurements of signals as they flow through neural circuits. However, the 3D nature of brain circuits and the speed of information transfer makes it difficult for neuroscientists to measure their properties with sufficiently high spatial and temporal resolution. During the NEUROGAIN ERC project, we developed a novel type of Acousto-Optic Lens (AOL)-based high-speed 3D laser scanner. This technology enables the focusing and scanning of a laser beam at 20-40 kHz. This scanning technology can be added to existing two-photon microscopes to enable 3D imaging of neurons and circuits with unprecedented spatio-temporal resolution. Moreover, it also automatically corrects for brain movement in real-time providing sharper images. This ERC PoC will facilitate commercialization of this 3D scanning technology by providing support to explore the markets in biosciences and beyond, protect the IP and facilitate early stage manufacture and assembly of AOL 3D scanners to supply biomedical researchers.

150 000 €

Start date: 2019-06-01, End date: 2020-11-30

We propose an unprecedented class of soft, self-assembled and self-motile micro-machines. The combined qualities of active fluids and colloidal liquid crystals can be leveraged to design intrinsically out-of- equilibrium hierarchal structures, or ‘Living’ Colloidal Liquid Crystals [LC]2. The study of colloidal interactions and self-assembly in active nematics has yet to be considered and constitutes an unexplored and inter-disciplinary application of the emerging sciences of active matter and colloidal liquid crystals. Activity will endow dynamical multi-scale colloidal structures with autonomous functionality, including self-motility, self-revolution and dynamical self-transformations, which are exactly the characteristics one would desire for a first generation of autonomous components of micro-biomechanical systems and soft micro-machines. As hybrids between biological active fluids and man-made materials, [LC]2 structures represent an early foray into ‘living’ metamaterials, in which active self-assembly of simple components produces a rich diversity of behaviours and the potential for autonomously tunable material properties, mimicking biological complexity. In particular, we hypothesize self-assembled [LC]2 dimer turbines, colloidal flagella and ant-like group retrieval. These systems represent a fundamentally innovative concept that we propose to drive nanotechnology into a new future of soft materials that biomimetically self-assemble and autonomously enact functions. It is our multiscale coarse-grained simulations and expertise in flowing active nematic fluids that generates the opportunity for this unique line of research.

1 402 345 €

Start date: 2019-12-01, End date: 2024-11-30

Ever increasing atmospheric CO2 concentrations and global emissions of 36 Gt/year impose unprecedented threats to the world’s ecosystem and endanger industrial human activities in their entirety. This AACCT project will establish a new advanced technology that facilitates efficient CO2 capture from air and results in a commercial, stand-alone prototype that will demonstrate its economical and ecological viability, outperforming all other emerging approaches to atmospheric CO2 capture. The technology takes advantage of unique, intrinsic micro- and macro-molecular structures of porous materials that were developed within the ERC SUPRAMOL and Science Foundation Ireland funded projects. These adsorbents reveal extraordinary affinity to CO2, are non-corrosive, non-toxic and are based on stable, cheap and abundant silica materials. The system operates in moist air whereby the CO2 recovery is facilitated at mild conditions under which the adsorbent is regenerated. These intrinsic characteristics in combination with the macro-structure of sub-millimetre pellets that enhances the ad/desorption kinetics, results in exceptionally low operational CO2 capture costs. The technology is modular and the number of capture units scales linearly with the desired CO2 quantity. It is not restricted to fixed locations or CO2 point sources and thus, can conceptionally lead to negative or net zero CO2 emissions. The AACCT technology will provide pure CO2 that can be sold, used or transformed within established or emerging chemical processes (i.e. methanol synthesis). Initially, it is envisaged that the systems, using low-grade waste heat, will be employed in energy-intensive industrial sectors requiring air circulation and cooling devices. A very modest adaptation of the AACCT prototypes can facilitate the reduction of Ireland’s greenhouse gas emissions by >10%, thus highlighting the potential impact and scalability of the proposed technology at European and global levels.

150 000 €

Start date: 2019-10-01, End date: 2021-09-30

In this project we will push the limits of microscale ultrasound-based technology to gain access to diagnostically important rare constituents of blood within minutes from blood draw. To meet the demands for shorter time from sampling to result in healthcare there is an increased interest to shift from heavy centralized lab equipment to point-of-care tests and patient self-testing. Key challenges with point-of-care equipment is to enable simultaneous measurement of many parameters at a reasonable cost and size of equipment. Therefore, microscale technologies that can take in small amounts of blood and output results within minutes are sought for. In addition, the high precision and potential for multi-stage serial processing offered by such microfluidic methods opens up for fast and automated isolation of rare cell populations, such as circulating tumor cells, and controlled high-throughput size fractionation of sub-micron biological particles, such as platelets, pathogens and extracellular vesicles. To achieve effective and fast separation of blood components we will expose blood to acoustic radiation forces in a flow-through format. By exploiting a newly discovered acoustic body force, that stems from local variations the acoustic properties of the cell suspension, we can generate self-organizing configurations of the blood cells. We will tailor and tune the acoustic cell-organization in novel ways by time modulation of the acoustic field, by altering the acoustic properties of the fluid by solute molecules, and by exploiting a novel concept of sound interaction with thermal gradients. The project will render new fundamental knowledge regarding the acoustic properties of single cells and an extensive theoretical framework for the response of cells in any aqueous medium, bounding geometry and sound field, potentially leading to new diagnostic methods.

1 999 720 €

Start date: 2019-11-01, End date: 2024-10-31

Resting on our demonstration of laser-driven nanophotonics-based particle acceleration, we propose to build a miniature particle accelerator on a photonic chip, comprising high gradient acceleration and fully optical field-based electron control. The resulting electron beam has outstanding space-time properties: It is bunched on sub-femtosecond timescales, is nanometres wide and coherent. We aim at utilizing this new form of all-optical free electron control in a broad research program with five exciting objectives: (1) Build a 5 MeV accelerator on a photonic chip in a shoebox-sized vessel, (2) Perform ultrafast diffraction with attosecond and even zeptosecond electron pulses, (3) Generate photons on chip at various wavelengths (IR to x-ray), (4) Couple quantum-coherently electron wavepackets and light in multiple interaction zones, and (5) Conduct radiobiological experiments, akin to the new FLASH radiotherapy and Microbeam cell treat-ment. AccelOnChip will enable five science objectives potentially shifting the horizons of today’s knowledge and capabilities around ultrafast electron imaging, photon generation, (quantum) electron-light coupling, and radiotherapy dramatically. Moreover, AccelOnChip promises to democratize accelerators: the accelerator on a chip will be based on inexpensive nanofabrication technology. We foresee that every university lab can have access to particle and light sources, today only accessible at large facilities. Last, AccelOnChip will take decisive steps towards an ultracompact electron beam radiation device to be put into the tip of a catheter, a potentially disruptive radiation therapy device facilitating new treatment forms. AccelOnChip is a cross-disciplinary high risk/high return project combining and benefiting nanophotonics, accelerator science, ultra-fast physics, materials science, coherent light-matter coupling, light generation, and radiology - and is based on my group’s unique expertise acquired in recent years.

2 498 508 €

Start date: 2020-10-01, End date: 2025-09-30

ACHIEVE focuses on the application of Excluded Volume Effect in cell culture systems in order to enhance Extracellular Matrix (ECM) deposition. It represents a new horizon in in vitro cell culture which will address major challenges in medical advancement and food security. ACHIEVE will elucidate extracellular processes which occur during tissue generation, identifying favourable conditions for optimum tissue cultivation in vitro. These results will be applied in the diverse fields of regenerative medicine, drug discovery and cellular agriculture which all require advancements in in vitro tissue engineering to overcome current bottlenecks. Effective in vitro tissue culture is currently limited by lengthy culture periods. An inability to maintain physiologic (in vivo) conditions during this lengthy in vitro culture leads to cellular phenotype drift, ultimately resulting in generation of an undesired tissue. Enhanced tissue generation in vitro will greatly reduce culture times and costs, effecting improved in vitro tissue substitutes which remain true to their original phenotype. The research will be addressed under four work-packages. WP1 will investigate biochemical, biophysical and biological responses to varying culture conditions; WP 2, 3 and 4 will apply results in the fields of Tissue Engineering, Drug Discovery and Cellular Agriculture respectively. Research will involve extensive characterisation of derived- and stem-cell cultures in varying conditions of expansion and relevant health and safety and preclinical testing. The five year programme will be undertaken at the National University of Ireland, Galway, a centre of excellence in tissue engineering research, at a cost of € 2,439,270.

2 076 770 €

Start date: 2020-09-01, End date: 2025-08-31

Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life. I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets. The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.

1 491 350 €

Start date: 2020-02-01, End date: 2025-01-31

AlzheimerAlzheimer’s disease (AD) is a crucial problem in our society, raising the need for new therapeutic targets. Evidence suggests multiple non-neuronal cells are implicated in the systemic deficits of AD, but the complex cellular diversity in the brain hampers the investigation of specific cells and their interactions. Moreover, the course of the disease is highly variable, due to multiple risk factors, including aging and gender, which have overlapping molecular signatures with AD that might be further masking disease mechanisms. I propose to expand the resolution from tissues to cellular environments, and to untangle overlapping molecular signatures of gender and aging, in order to unmask molecular mechanism of AD. Technological advances in genomics and imaging, including the single nucleus RNA-sequencing methods developed by me, as well as my expertise in computational analysis and CRIPSR perturbations, provide a unique opportunity to address this challenge. I obtained preliminary results strongly suggesting that multiple cell types are indeed altered in AD brains of mice and humans, and that gender, aging, and AD have overlapping molecular features. I hypothesize that age-dependent cellular/molecular alterations are key drivers of cognitive decline, and that the dynamics of these alterations determine risk and resilience levels in individuals. We will test this hypothesis by: 1) Charting the cellular microenvironments and tissue topology of the human AD brain, to reveal cells, pathways, and cellular interactions driving AD; 2) Mapping the dynamic cellular/molecular trajectories in aging and AD in w.t. and AD mice, to untangle AD, aging, and gender dimorphism; and 3) Identifying regulators of cognitive resilience and decline in AD and aging, and connecting genes to function by detailed mechanistic investigations in vivo. Overall, our innovative proposal is expected to advance our understanding of AD mechanism, and the link to aging and gender dimorphism.

1 500 000 €

Start date: 2020-06-01, End date: 2025-05-31

Alzheimer's disease (AD) is a heterogeneous disease in which multiple detrimental factors contribute to cognitive loss and disease escalation. Currently there are no effective therapies for AD. Targeting any single symptom of disease-escalating factor (e.g. amyloid beta, tau, neuroinflammation etc.), even if successful, is not sufficient to modify the disease, as seen in the multiple failures of recent phase-III clinical trials. Thus, there is a desperate need for new approaches for development of AD therapeutics, which will be more comprehensive and not etiology-specific. Using single cell genomic analysis of the immune system in AD mouse models, we discovered a novel microglia type, disease associated microglia (DAM), intrinsic immune cells of the brain that fight AD and neurodegenerative disease. There are several revolutionary aspects to our approach to modify AD course. Fundamentally, based on our unique DAM pathways and target discovery platform we will develop novel AD-immunotherapy for boosting the brain’s innate neuroprotective mechanisms that fight neurodegeneration in AD. Development of targets that boost DAM cells is a major activity of this PoC plan, and we are in different phases of development of several targets that increase DAM activity including advanced stages of the targets Trem2 and P2ry12. The first goal of this PoC grant is to develop and strengthen our IP around AD immunotherapy targets. The second goal is to design a viable and scalable business model with venture capital and establish a startup (ADAMtheraputics) that will translate our novel technology for effective AD-immunotherapy for Alzheimer patients. We believe that our unique approach of targeting the brain’s intrinsic protective immune cells, to boost their activity and numbers, will dramatically impact AD therapy.

150 000 €

Start date: 2019-10-01, End date: 2021-03-31

Communication networks have become a critical infrastructure of our digital society. However, with the explosive growth of data-centric applications and the resulting increasing workloads headed for the world’s datacenter networks, today’s static and demand-oblivious network architectures are reaching their capacity limits. The AdjustNet project proposes a radically different perspective, envisioning demand-aware networks which can dynamically adapt their topology to the workload they currently serve. Such self-adjusting networks hence allow to exploit structure in the demand, and thereby reach higher levels of efficiency and performance. The vision of AdjustNet is timely and enabled by recent innovations in optical technologies which allow to flexibly reconfigure the physical network topology. The goal of AdjustNet is to lay the theoretical foundations for self-adjusting networks. We will identify metrics that serve as yardstick of what can and cannot be achieved in a self-adjusting network for a given demand, devise algorithms for online adaption, and validate our framework through case studies. Our novel methodology is motivated by an intriguing connection of self-adjusting networks to known datastructures and to information theory. AdjustNet comes with significant challenges since, similar to self-driving cars, self-adjusting networks require human network operators to give away control, and since more autonomous network operations may lead to instabilities. AdjustNet will overcome these risks and achieve its objectives by pursuing a rigorous approach, devising a theoretical well-founded framework for self-adjusting networks which come with provable guarantees and incorporate self–protection mechanisms. The PI is well-equipped for this project and recently obtained first promising results. As the community is currently re-architecting communication networks, there is a unique opportunity to bridge the gap between theory and practice, and have impact.

1 670 823 €

Start date: 2020-03-01, End date: 2025-02-28

Digital technology has fundamentally changed the action repertoire of political campaigning and advocacy in the last decade. Despite its fundamental role in contemporary political strategy and potential to affect the quality of democracy, there is still little systematic evidence to assess and compare the real effects of online and offline advocacy tools. ADVODID will implement the first large-scale quantitative project designed to provide rich correlational and causal evidence on the effects of advocacy on citizens and policymakers, in both online and offline settings. It sets out to address - theoretically and empirically - the potentials and challenges for modern democracies that arise from digital advocacy tools. Its novelty lies in analyzing the use, impact and democratic consequences of digital advocacy strategies by assessing interactions of advocacy groups with both citizens and political representatives in a diverse set of eight countries (Australia, Chile, Denmark, India, the Netherlands, Spain, the UK, and the US). ADVODID will collect data on the advocacy agenda and strategy use of at least 400 carefully sampled advocates in these countries, and will assess agenda congruence with political and public agendas, and their dynamic development over time. Correlational analyses of different measures of advocacy success will be complemented by field experiments in cooperation with advocates in two countries, to supply causal evidence on how advocacy affects the positions and actions of policymakers and citizens. The project’s rich datasets will be used to assess and refine theories of democratic representation and the role of digital advocacy across different types of policy issues. ADVODID will greatly advance understanding of how modern advocacy impacts its target audiences and potentially changes participatory democracy. Its findings will have interdisciplinary and social relevance and inform ways to strengthen representative democracy in an online age.

1 986 922 €

Start date: 2021-08-01, End date: 2026-07-31

The historiography of Euro-American abolitionism is so vast that it has a history of its own (Brown 2006). By contrast, research on African abolitionism is a narrow field focused primarily on European anti-slavery activities. It presupposes that when Europe abolished slavery in Africa, Africans became abolitionists. This conclusion is unfounded. Many general questions have never been asked: When and where did African abolitionist movements develop? Who are the main ideologues of African abolitionism? How did abolitionism spread, among which groups? What forms of political struggle did African anti-slavery give rise to? While individual African abolitionists and regional movements have attracted limited attention, there is no major review of the phenomenon on a continental scale. AFRAB fills this gap. It contributes to African and global history and slavery studies by analyzing and comparing African abolitionist ideas and anti-slavery movements, the long-term consequences of European abolitionism, and the resilience of pro-slavery discourses.

2 499 951 €

Start date: 2020-10-01, End date: 2025-09-30

Drones are disrupting industries, such as agriculture, package delivery, inspection, and search and rescue. However, they are still either controlled by a human pilot or heavily rely on GPS for navigating autonomously. The alternative to GPS are onboard sensors, such as cameras: from the raw data, a local 3D map of the environment is built, which is then used to plan a safe trajectory to the goal. While the underlying algorithms are well understood, we are still far from having autonomous drones that can navigate through complex environments as good as human pilots. State-of-the-art perception and control algorithms are mature but not robust: coping with unreliable state estimation, low-latency perception, real-time planning in dynamic environments, and tight coupling of perception and action under severe resource constraints are all still unsolved research problems. Another issue is that, because battery energy density is increasing at a very slow rate, drones need to navigate faster in order to accomplish more within their limited flight time. To obtain more agile robots, we need faster sensors and low-latency processing. The goal of this project is to develop novel scientific methods that would allow me to demonstrate autonomous, vision-based, agile quadrotor navigation in unknown, GPS-denied, and cluttered environments with possibly moving obstacles, which can be as effective in terms of maneuverability and agility as those of professional drone pilots. The outcome would not only be beneficial for disaster response scenarios, but also for other scenarios, such as aerial delivery or inspection. To achieve this ambitious goal, I will first develop robust, low-latency, multimodal perception algorithms that combine the advantages of standard cameras with event cameras. Then, I will develop novel methods that unify perception and state estimation together with planning and control to enable agile maneuvers through cluttered, unknown, and dynamic environments.

2 000 000 €

Start date: 2020-09-01, End date: 2025-08-31

As global climates warmed ca. 10,000 years ago came a remarkable convergent transformation of human lifestyles that occurred independently in multiple continents and human populations. This transition from hunter-gatherer subsistence to food-production catalysed large-scale population growth, offering the opportunity for increased rates of adaptation, but also rapidly presented a large number of independent human populations with a new evolutionary challenge. This project will use ancient population genomics—the only way to directly reconstruct human genetic evolution—to study whether evolutionary processes during the agricultural transition differed in differed regions. Which genomic adaptations were associated with the agricultural transition? Did adaptation to hunter-gatherer and agricultural lifestyles act on similar genetic architecture in different instances? To which extent did adaptation in domestic dogs—the only species domesticated prior to the agricultural transition—occur in convergence with humans? To answer these questions, the project will generate ancient genomic data from pre-agricultural and early agricultural populations from multiple human- and domestic dog populations from Africa, Central America, and Southeast Asia. This will be achieved with direct sequencing as well as a new human ~850,000 SNP capture panel designed to avoid bias towards Eurasian ancestry. We will also develop new computational methods robust to the challenges posed by ancient genomes to identify adaptive admixture, analyse copy number variation, test continuous population models, and statistically assess convergence in the genomic architecture of adaptation. Leveraging cutting-edge ancient genomics and two model organisms for the genomic basis of phenotypic variation, this project aims to reconstruct the universal evolutionary phenomena underpinning a watershed evolutionary episode that shapes global biodiversity and the human condition to this day.

1 500 000 €

Start date: 2019-11-01, End date: 2024-10-31

The Type 6 secretion system (T6SS) allows Gram-negative bacteria to deliver toxins into both eukaryotic and bacterial target cells and thus cause disease or kill competitors. T6SS is composed of four main parts: a membrane complex, a baseplate and a long spring-like sheath wrapped around an inner tube. Sheath contraction generates a large amount of energy to push the tube with associated toxins through the baseplate and membrane complex out of the cell. However, the reach of the T6SS tube is limited and thus a direct contact with the target membrane and precise positioning of T6SS assembly is required for protein translocation. In this proposal, we will unravel principles of spatial and temporal coordination of T6SS assembly that we have recently observed in several bacterial species. We will study how cells sense attacks from neighboring bacteria to dynamically localize its T6SS. We will describe how bacteria initiate and position T6SS assembly in response to physical cell-cell interactions. We will identify the principles and the role of T6SS localization in intracellular pathogens. Using genetic and biochemical approaches, we will identify and characterize proteins interacting with the core components of T6SS and test their role in initiation and positioning of T6SS assembly. We will search for peptidoglycan remodeling enzymes required for T6SS assembly. We will use advanced microscopy techniques to describe dynamic localization of proteins upon T6SS activation to establish the order of their assembly. We will quantify how much T6SS aiming increases efficiency of protein delivery and T6SS function during bacterial competition and pathogenesis. Overall, we will unravel novel principles of spatial and temporal control of localization of protein complexes and show how this allows bacteria to quickly respond to external cues and interact with their environment.

2 493 650 €

Start date: 2021-01-01, End date: 2025-12-31

"Digital geometry representations are nowadays a fundamental ingredient of many applications, as for instance CAD/CAM, fabrication, shape optimization, bio-medical engineering and numerical simulation. Among volumetric discretizations, the ""holy grail"" are hexahedral meshes, i.e. a decomposition of the domain into conforming cube-like elements. For simulations they offer accuracy and efficiency that cannot be obtained with alternatives like tetrahedral meshes, specifically when dealing with higher-order PDEs. So far, automatic hexahedral meshing of general volumetric domains is a long-standing, notoriously difficult and open problem. Our main goal is to develop algorithms for automatic hexahedral meshing of general volumetric domains that are (i) robust, (ii) scalable and (iii) offer precise control on regularity, approximation error and element sizing/anisotropy. Our approach is designed to replicate the success story of recent integer-grid map based algorithms for 2D quadrilateral meshing. The underlying methodology offers the essential global view on the problem that was lacking in previous attempts. Preliminary results of integer-grid map hexahedral meshing are promising and a breakthrough is in reach. We identified five challenges that need to be addressed in order to reach practically sufficient hexahedral mesh generation. These challenges have partly been resolved in 2D, however, the solutions do not generalize to 3D due to the increased mathematical complexity of 3D manifolds. Nevertheless, with our experience in developing and evaluating the 2D techniques, we identified the key properties that are necessary for success and accordingly propose novel volumetric counterparts that will be developed in the AlgoHex project."

1 482 156 €

Start date: 2020-02-01, End date: 2025-01-31

ALGOSOC develops a new approach to understanding and responding to the consequences of machine learning algorithms for contemporary societies. Rapid advancements in machine learning technologies are transforming social and political life in ways that uniquely challenge how we live in relation to others. The life chances of a person are now intimately connected to the attributes that an algorithm has learned from the data patterns of unknown others. From judgements in the criminal justice system to decisions on treatment pathways in health, the outputs of algorithms have become pivotal to the decisions and adjudications on the probable futures of individuals. While there is substantial academic and public emphasis on defining ethical codes of conduct for algorithmic decisions, there is a lack of attention to how machine learning algorithms remake the ethical relations that define a society. In short, existing research is focused on limiting the harms of the actions of algorithms, whereas ALGOSOC focuses on how algorithms are redefining the thresholds of what harmful, good, bad, or risky behaviour means in a society. The ALGOSOC project will examine how 21st century machine learning algorithms are learning to recognize, to attribute, and to infer the characteristics of entities (people, groups, and objects). In order to do this, the project will conduct a series of path-defining studies of societal domains of machine learning that, though they share algorithms in common, have not previously been researched in combination: behavioural biometrics and biomedical object recognition; consumer recommendation and criminal justice scoring; oncology treatment pathways and anomaly detection for security. The ALGOSOC project will provide new social science knowledge of what is taking place as machine learning algorithms travel across different domains and sites, and how precisely they learn by their exposure to different worlds of data.

2 150 686 €

Start date: 2020-10-01, End date: 2025-09-30

Organ colonization is the most inefficient step of metastasis. However, once a few cancer cells manage to re-initiate their growth in the brain, the initial naïve microenvironment, which was not favouring and even actively limiting the number of potential metastasis initiating cells, is slowly rewired into a different ecosystem with pro-metastatic properties. In this project (ALTER-brain), we will study the biology of microenvironment reprogramming to explore innovative ways of treating metastasis. Microenvironment reprogramming relies on altered molecular patterns that emerge in specific brain cell types simultaneously to the outgrowth of metastases. Dissecting the biology of these emerging patterns and their functional consequences could provide the basis to prevent metastasis but also to treat advances lesions. A key objective of ALTER-brain is the identification of newly established functional networks among previously non-connected components of the microenvironment that are critical to nurture tumour growth. This research proposal focuses on metastasis in the brain given its rising incidence, poor therapeutic options and short survival rates upon diagnosis. ALTER-brain will use novel (i.e. spontaneous metastasis) and clinically relevant (i.e. relapse after therapy) experimental mouse models of brain metastasis combined with genetically engineered mice in which we will target specific components of the microenvironment. In addition, we will apply novel lineage tracing technologies to understand the origin and emerging heterogeneity of the reprogrammed microenvironment. Given the clinical relevance of our research, human brain metastasis provided by our clinical network will be used to validate key findings. ALTER-brain will identify key principles underlying the unknown biology of the brain under a specific pathological pressure that might be translated to other highly prevalent disorders affecting this organ in the future.

1 897 437 €

Start date: 2020-07-01, End date: 2025-06-30

Four years ago, the LIGO/Virgo observation of a black-hole binary merger heralded the dawn of gravitational-wave astronomy. The promise of future observations calls for an invigorated effort to underpin the theoretical framework and supply the predictions needed for detecting future signals and exploiting them for astronomical and astrophysical studies. Ampl2Einstein will take ideas and techniques from recent years' dramatic advances in Quantum Scattering Amplitudes, creating new tools for taking their classical limits and using it for gravitational physics. The powerful `square root' relation between gravity and a generalization of electrodynamics known as Yang--Mills theory will play a key role in making this route simpler than direct classical calculation. We will transfer these ideas to classical General Relativity to compute new perturbative orders, spin-dependent observables, and the dependence on the internal structure of merging objects. We will exploit symmetries and structure we find in order to extrapolate to even higher orders in the gravitational theory. We will make such calculations vastly simpler, pushing the known frontier much further in perturbation theory and in complexity of observables. These advances will give rise to a new generation of gravitational-wave templates, dramatically extending the observing power of detectors. They will allow observers to see weaker signals and will be key to resolving long-standing puzzles about the internal structure of neutron stars. We will apply novel technologies developed for scattering amplitudes to bound-state calculations in both quantum and classical theory. Our research will also lead to a deeper understanding of the classical limit of quantum field theory, relevant to gravitational-wave observations and beyond. The transfer of ideas to the new domain of General Relativity will dramatically enhance our ability to reveal new physics encoded in the subtlest of gravitational-wave signals.

2 372 571 €

Start date: 2021-01-01, End date: 2025-12-31

How did politics and inequality work in prehistoric Europe? Traditionally, politics has been seen in terms of discrete political ranks identified through differential treatment of individual burials. But this results in classifying much of prehistory, where the dead were treated in ways which effaced individual identity, as egalitarian. The result is an artificially dichotomous history: Neolithic people had landscapes, rituals and ancestors, Bronze and Iron Age people had politics and inequality. In the last two decades this approach has been strongly critiqued. Burial treatment rarely relates to status so directly; the dead serve many different political roles. Inequality in pre-state groups rarely consists of clear strata; inequality and equality exist in tension within groups. Inequality may have been present throughout European prehistory, but manifest situationally through differential life chances, kinship, ritual or ancestorhood, rather than overtly through political command, wealth or identity. But this new perspective has never been tested empirically. This project tests alternative models of prehistoric inequality and deathways. To investigate social relations in life, it uses osteobiography, reconstructing life stories from skeletons through scientific data on identity, health, diet, mobility and kinship. To understand deathways, it employs a second new methodology, funerary taphonomy. Combining osteobiography and taphonomy allows us to connect ancient lives and deaths. Peninsular Italy provides a substantial test sequence typical of much of Europe. For each of three key periods (Neolithic, 6000-4000 BC; Final Neolithic to Early Bronze Age, 4000-1800 BC; Middle Bronze Age to Iron Age, 1800-600 BC), 200+ individuals will be analysed. The results will allow us to evaluate for the first time how inequality affected lives in prehistoric Europe and what role ancestors played in it.

1 943 548 €

Start date: 2020-10-01, End date: 2024-09-30

Chromosome segregation errors cause aneuploidy, a state of karyotype imbalance that accelerates tumor formation and impairs embryonic development. Even though mitotic errors have been studied extensively in cell cultures, the mechanisms generating various errors, their propagation and effects on genome integrity are not well understood. Moreover, very little is known about mitotic errors in complex tissues. The main goal of this project is to uncover the molecular origins of mitotic errors and their contribution to karyotype aberrations in healthy and diseased tissues. To achieve our goal, we have assembled an interdisciplinary team of experts in molecular and cell biology, cell biophysics, chromosomal instability in cancer, and theoretical physics. Our team will introduce novel approaches to study aneuploidy (superresolution microscopy, optogenetics, laser ablation, single cell karyotype sequencing) and apply them to state-of-the-art tissue cultures (mammalian organoids and tumoroids). In close collaboration, Tolić will establish assays to detect and quantify error types in cells, and Kops and Amon will use the assays on various healthy and cancer tissues. Tolić and Kops will uncover the molecular origins of errors, their propagation and impact on genome integrity, while Amon will lead the investigation of the mechanisms that ensure high chromosome segregation fidelity in healthy tissues. Interwoven in these collaborations are the efforts of Pavin, who will develop a theoretical model to describe the origin of errors and to quantitatively link chromosome segregation fidelity in single cells and tissues. Model and experiment will continuously inspire each other, to achieve deep understanding of how mitotic errors arise, how they propagate and how they impact on cell populations. Thus, the extensive sets of expertise present in our team will be combined and expanded with novel technologies to tackle the big challenge of the origins of aneuploidy in humans.

9 999 750 €

Start date: 2020-04-01, End date: 2026-03-31

The detection of circulating disease biomarkers in bodily fluids, also known as liquid biopsy, has taken important strides toward the implementation of personalized medicine. However, it still suffers from low sensitivity and high costs, which render its clinical implementation not practical or affordable. In particular, the identification and quantification of oligonucleotide biomarkers is hampered by the need to employ long- and short-read sequencing tools that are expensive, require highly trained personnel, and are prone to error. Nonetheless, the recent clinical breakthroughs demonstrating the importance of detecting cancerous or viral biomarker to susceptibility, onset, and aggressiveness of the disease, motivate the need for further research that could render their detection simpler, cheaper, and thus more widely available. By leveraging the intrinsic amplification capability of surface enhanced Raman scattering (SERS), in ANFIBIO I will address the issues of low sensitivity and high costs by combining plasmonic nanoparticles synthesized ad hoc to maximize SERS signal amplification with direct SERS sensing and machine learning tools for the rapid analysis of the complex spectral responses obtained by screening bodily fluids for specific target biomarkers. I will focus in particular on prostate cancer (PCa) DNA and influenza A viral (IAV) RNA in blood, urine, and saliva, to quantify and correlate their amounts to those detected in tissues and cells. At completion, the proposed work will deliver a breakthrough sensing technology capable of detecting and quantifying cancerous and viral biomarkers in bodily fluids, with minimal sample pretreatment, no target amplification, and that uses SERS as novel and reliable transduction mechanism with distinct advantages over those currently employed. Furthermore, the fundamental insight garnered will likely assess the feasibility of using direct SERS sensing to develop beyond-third generation sequencing technologies.

2 725 510 €

Start date: 2021-06-01, End date: 2026-05-31

Recent studies of halide perovskite semiconductors (SCs) showed that they exhibit a unique combination of very-low defect density, self-healing properties and low exciton binding energies that result in excellent photovoltaic activity. I hypothezise that the fundamental property that sets the halide perovskites apart from conventional SCs and gives rise to their beneficial properties is strongly anharmonic lattice dynamics. Large amplitude, local polar fluctuations that result from lattice anharmonicity localize the electronic states and enhance the screening of electric charges within the material. In other words, in some aspects, halide perovskites behave more like a liquid than a crystalline solid. Stimulated by the recent discoveries on halide perovskites, I aim to generalize our understanding of the relationship between lattice anharmonicity and the electronic properties of SCs. The potential outcome of this investigation will be a novel scheme to design SCs with desirable properties where lattice anharmonicity is used as a new material-engineering tool. My strategy is to perform comparative studies in both inorganic ionic crystals and small-molecule organic crystals. We will use low-frequency Raman spectroscopy to quantify anharmonic lattice dynamics and compare between different crystals to identify the factors that induce anharmonicity in solids. Photoluminescence, reflectance, time-resolved terahertz and impedance spectroscopies will be used to probe the SCs optical properties, carrier mobilities and lifetimes, and their dielectric response. I expect to find that as anharmonicity increases, the dielectric response and carrier lifetimes increase while carrier mobility decreases. Finally, we will develop a modulated Raman spectroscopic methodology that will identify specific lattice motions that are coupled to band-edge carriers, thus elucidating the microscopic mechanism of carrier-lattice interactions.

1 700 000 €

Start date: 2019-11-01, End date: 2024-10-31

"In a time of accelerating human-caused ecological catastrophe, questions of organizational resilience have become extremely timely. In bringing the archaeological perspective of a 4200-year timespan, ANTHEA seeks to to radically alter our knowledge of resilient forms of self-organisation in past land-use regimes and human-nature entanglements. Based on seven case study areas, ANTHEA will show how collaborative institutions of common land use were organized in the North European heathland regimes (3200 BC-AD 1000), with a particular emphasis on their earliest emergence, their adaption to internal and external factors as well as their ecological, temporal, spatial, and social fabric. More than 4,000 years ago, farming communities across northern Europe began the first fire-based expansion of naturally occurring heather. Pollen evidence suggests that some of these grazing areas, spanning thousands of hectares, existed until the 18th-19th century. Without frequent intervention and management, anthropogenic heathland will turn into forest. So the survival of these areas suggests the existence of highly specialised forms of social organization with the unique capacity to persist. Still, we know little about the actual stability of these heathlands or what caused their unprecedented resilience. By shifting attention away from seeing institutional robustness as equilibrium, stability and continuity and placing the questions of instability, uncertainty, and areal flexibility at the centre, ANTHEA envisages a new cultural history of heathlands that breaks with rooted ideas of these areas being marginal and underdeveloped. ANTHEA is truly multidisciplinary and links landscape and settlement archaeology with paleoenvironmental modelling, social anthropology and philosophy. Moreover, the project introduces a pioneering theoretical and methodological advancement in the temporality of resilience, to be made usable in contemporary land-use policies. The long-term perspective will allow detailed historical trajectories to be established of how common land-use institutions emerged and reorganized according to changing circumstances, challenging the ""tragedy of the commons"" narrative."

1 499 457 €

Start date: 2020-08-01, End date: 2025-07-31

Pain is one of the most problematic symptoms of rheumatic disease such as rheumatoid arthritis (RA) and fibromyalgia (FM). We have earlier discovered that antibodies (immunoglobulin, IgG) purified from blood of seropositive rheumatoid arthritis (RA) patients induce pain-like behavior when transferred to mice, independent of inflammatory reactions. Even though FM is not considered an autoimmune disease, it has been suggested that neuroimmune dysregulation contribute to the pathogenesis. Therefore, we purified IgG from FM patients and found that also IgG from FM patients, but not healthy controls, have pronociceptive properties in mice, and surprisingly, bind to satellite glial cells in dorsal root ganglia. Our findings highlights the importance of expanding our view on which chronic pain conditions that could have an underlying autoimmunity as part of the pain pathology. Thus, the overall objective of this project is to investigate both general, and disease specific, pain-inducing mechanisms mediated by RA and FM IgG. Objective 1. Investigate how IgG from RA and FM patients induce pain-like behavior after transfer to mice Objective 2. Search for RA and FM IgG induced maladaptive changes in sensory neurons that mediate hyperexcitability and long-term pain-like behavior Using patient and healthy control samples, in vivo mouse behavioral assays, primary neuronal and non-neuronal cell cultures together with stat-of-the-art methodology, we will investigate how RA and FM-associated autoantibodies alter sensory neuronal excitability. If successful our project will not only challenge the view of how antibodies can contribute to pain but also pin-point specific mechanisms by which disease-relevant antibodies induce and maintain pain independent of previously described inflammatory mechanisms. Such findings promise to resolve currently unanswered questions concerning symptoms of pain in RA and FM, and to pave the way for the development of new pain-relieving therapies.

1 993 763 €

Start date: 2020-10-01, End date: 2025-09-30

The main aim of the ANTIGONE project is to investigate how the disappearance of practices for managing shared environmental resources played a role in the abandonment and political marginalisation of European mountain areas from the 18th c onwards. The legacy of these processes can be seen in population levels in these areas, and in the worsening of their natural and cultural heritage. Current policies – aiming to promote their ‘heritagisation’ – do not seem likely to be more effective, in the long-term, as development interventions than the drive for rationalisation in the 19th c. and modernisation in the 20th c. A new historical perspective is needed which addresses the process of abandonment and marginalisation in its entire complexity. ANTIGONE will analyse the critical period from the 18th to the 21st c. and provide new insights into the links between individuals, communities, central States and landscape, grounded in a new understanding of the relationship between practices, resources and objects. By means of archaeological, historical, environmental, ethnological analyses, and through the comparison of case studies from European mountain areas, ANTIGONE aims to verify if alleged ‘improvement’ practices involved not just changes in management technique, but also contributed to decline in the sharing of work, time and space, with knock-on effects on the social dimension of the whole historic system. Through its multidisciplinary approach ANTIGONE aims at provide: new knowledge on the historical mechanisms underlying the abandonment of mountain and, more broadly, rural areas, as a key to understanding marginalisation; new knowledge on landscapes, practices and their features; a new methodological toolbox for interdisciplinary investigations driven by archaeology; a new role for archaeology, beyond the acknowledged one as a heritage science; new contributions to community based policies for local sustainable development and landscape management.

1 498 000 €

Start date: 2020-11-01, End date: 2025-10-31

Antarctic sea ice is a critical component of Earth’s climate system. Seasonal fluctuations support unique ecosystems and impact planetary albedo, ocean-atmosphere exchanges of heat and climatically-active gases (e.g. CO2), and formation of intermediate and deep water masses which create the world’s largest sink of heat and carbon. The properties of the sea-ice pack are complex: despite its climatic significance, Antarctic sea ice is challenging to observe and to model, leading to low confidence in future projections in a warming climate. The geological record offers a longer-term context for recent trends. At the last glacial maximum (LGM) a likely doubling of Antarctic sea-ice extent relative to today is hypothesised to have driven an ocean drawdown of atmospheric CO2. However, a combination of sparse empirical datasets and uncertainties in sea-ice modelling means that the properties and climatic impacts of the LGM Antarctic sea-ice pack are poorly understood. The narrow focus of the geological record on key primary producers and grazers further limits our understanding of Antarctic ecosystem responses to changes in sea ice. ANTSIE will exploit a unique biological archive of Antarctic sea-ice conditions to generate a novel ecosystem perspective on the patterns and properties of sea ice during and since the LGM. ‘Antarctic mumiyo’ sequences are preserved remains of regurgitated stomach contents from snow petrels, which feed within and at the edges of the sea-ice pack. A network of mumiyo sequences, which sample across the climatically important Weddell Sea region, will be geochemically analysed to determine snow petrel diet and sea-ice properties with unprecedented century-scale resolution. The results will be used to evaluate new state-of-the-art simulations of the LGM sea-ice pack. By integrating multi-disciplinary perspectives, ANTSIE will provide new understanding of Antarctic sea-ice controls and impacts, to facilitate improved confidence in future project.

1 999 929 €

Start date: 2020-06-01, End date: 2025-11-30

In our quest to fully understand the processes that shape the genomic variation of species, describing variation of the past is a fundamental objective. However, the origins and the extent of great ape variation, the genomic description of extinct primate species and the genomic footprints of introgression events all remain unknown. Even today, and in contraposition to human evolutionary biology, the almost null presence of ancient great ape samples has precluded a comprehensive exploration of such diversity. Here, I present two approaches that will expose great ape diversity throughout time and will allow me to compare the genomic impact of introgression events across lineages. First, I would like to take advantage of ancient ape samples that will provide us with a direct view of the genomes of extinct populations. Second, I would like to exploit current and recent diversity to indirectly access the parts of extinct ape genomes that became hybridized with current species in the past. For the latter, we will analyse hundreds of non-invasive samples taken from present-day great apes as well as historical specimens. Altogether, this information will enable me to decipher novel genomes that until now have been lost in time. In this way, I will be able to properly understand the origins and dynamics of genomic variants and to study how admixture has contributed to today´s adaptive landscape. By completing this proposal and performing analogies to the human lineage, fundamental insights will be revealed about (i) the spatial-temporal history of our closest species and (ii) the functional consequences of introgressed events. On top of that, these results will help to annotate functional consequences of novel mutations in the human genome. In so doing, a fundamental insight will be provided into the evolutionary history of these regions and into human mutations with multiple repercussions in the understanding of evolution and human biology.

1 896 875 €

Start date: 2020-06-01, End date: 2025-05-31

Mathematical models of human decision making are a widely used tool for advising policy makers and industry by making predictions of future demand for products and services. The reliability of the predictions depends on the robustness of the underlying mathematical models. A very active field of academic research is concerned with the refinement of existing model structures and the development of new approaches. Over the last two decades, fuelled by the availability of ever more powerful computing resources, there has been a major step change in the mathematical complexity of these models. However, the vast majority of real world users of choice models, and also many academic users, lack a programming background. This means that most users are restricted to those models which are covered in existing software, and models developed by analysts who lack programming skills fail to be used in practice. A core output from the ERC-CoG grant DECISIONS (615596) has been the development of the Apollo package. Apollo is a powerful open source solution for the estimation and application of choice models. The current PoC proposal seeks to fully explore the innovative research that led to the development of Apollo and to take the first steps in establishing Apollo as a next generation tool for choice modelling, with full customisation possibilities including for inexperienced users. We propose to make changes to the existing implementation of Apollo to provide users with an easy to use template for developing code and to create a system for testing user-developed functions for new models, standardise the code used in them, and incorporate them in releases of new versions of Apollo to make them available to other users. In addition, we propose to introduce a pay-to-program service where users can pay to have new features developed. These features will be released to all users after an embargo period during which they are limited to the user who paid for their development.

150 000 €

Start date: 2020-02-01, End date: 2022-01-31

Most chemical reactions in lifeforms take place in aqueous environments and probing biochemical molecules and their reactions in the aqueous phase is indispensable for advancing fundamental and applied science. Equally, intermolecular effects involving chiral complexes are highly relevant to life sciences, where hydration and chiral recognition are fundamental biochemical processes, typically occurring at aqueous interfaces. All of these processes are driven by electronic structure interactions with water molecules and are intimately connected with aqueous-phase electron binding energies. The prime experimental tool to access these properties is photoelectron spectroscopy (PES). With the recent invention of liquid-microjet-(LJ) PES, compatible with highly volatile liquid water and aqueous solutions, this technique has significantly contributed to modern water research, providing important insights into formerly elusive water properties, such as absolute energetics and solute interfacial distributions. I propose to explore chirality in aqueous solution using a novel aspect of photoelectron emission: photoelectron circular dichroism (PECD). It is site-specific and sensitive to chemical environment and structure. Furthermore, PECD exceeds absorption-based chiroptical signals by orders of magnitude, allowing application to dilute samples, potentially including interfacial layers, akin to PES. PECD has been demonstrated for isolated chiral molecules and clusters, and measurement of PECD effects in aqueous solution would mark a scientific breakthrough. The aim of AQUACHIRAL is to combine LJ-PES with PECD to (1) probe aqueous-phase chirality using enantioselective electronic-structure fingerprints of solutes and to (2) follow the stereochemistry of prominent chemical reactions in aqueous solution, e.g. slow glucose mutarotation. To achieve this, experimental technology must be extended, with novel liquid jets and electron detection systems being developed and optimized.

2 490 250 €

Start date: 2021-01-01, End date: 2025-12-31

Compelling evidence is now emerging that tropical environments were cradles of innovation and complexity from prehistory to the present. Tropical forests in particular have long been considered marginal and inhospitable, but recent work suggests that several critical milestones were achieved in these landscapes. Vast expanses were terraformed by increasingly complex societies, often in a quest to mitigate the sharp seasonality of the monsoon. Ostensibly wild and pristine rainforests are now characterised as managed 'gardens'. The giant low-density settlement complexes of 'rainforest civilisations' anticipate the sprawling megacities of our contemporary world, and offer a laboratory for understanding the profound challenges that they create. To date, these emerging perspectives have largely been driven by advances in palaeobotany, archaeogenetics, isotopic analyses, and contemporary rainforest ecology. Remote sensing has so far played only a modest role in this broader agenda, in spite of the unique capability of lidar technology to 'strip away' vegetation and reveal archives of human activity inscribed in the Earth's surface. This program will tackle the core problems that currently constrain the 'lidar revolution' in archaeology: We will use a new generation of lidar technologies to greatly expand coverage in Southeast Asia, home to many of the most important and understudied rainforest landscapes. We will develop open access frameworks and infrastructures for aggregating, sharing and collaborating on new and existing lidar datasets. We will build on recent advances in artificial intelligence to develop generic models for automation and analysis, in order to move beyond localised, culturally-specific lidar applications. The net result of this work will be to create consistent, comparable datasets of human impacts on the Earth's surface, with a view to understanding trajectories of innovation and complexity in the tropical world from the deep past to the present.

2 748 285 €

Start date: 2020-10-01, End date: 2025-09-30

Large-scale genome-wide association studies (GWAS) have yielded thousands of genetic as-sociations to heritable traits, but for most common diseases, these signals collectively explain only a small fraction of phenotypic variation. The phenotypic impact of recent, rare genetic variants, in particular, is poorly understood, but currently available data sets and analytical tools cannot be used to effectively study this class of variation. To address this problem, we propose to develop new computational methodology that will enable studying the phenotypic role of recent, rare genetic variation. This will improve our understanding of the architecture of heritable complex traits, inform the design of future studies, and increase our ability to detect novel associations. This project will address three specific aims. The first aim is to devise new methods to accurately reconstruct the complex network of genealogical relationships of individuals using high/low-coverage sequencing or microarray data. The second is to leverage these genealogical structures to infer the presence of unobserved genetic variation, with the goal of analyzing variance components of narrow sense heritability attributable to rare variants and studying the evolutionary history of heritable traits. Finally, in the third aim, we will develop new approaches to detect association to both rare and common variants, increasing the statistical power of GWAS methodology.

1 499 665 €

Start date: 2020-01-01, End date: 2024-12-31

ArmEn seeks to establish a new framework for studying the southern Caucasus, eastern Anatolia and northern Mesopotamia (CAM) as a space of cultural entanglements between the 9th to 14th centuries. It argues that this region is key to understanding the history of medieval Eurasia but has so far been completely neglected by the burgeoning field of Global Middle Ages. The CAM was on the crossroads of expanding Eurasian empires and population movements, but was removed from major hubs of power. Poly-centrism; political, ethno-linguistic, and religious heterogeneity; frequently shifting hegemonic hierarchies were key aspects of its, nevertheless, inter-connected landscape. This fluidity and complexity left its mark on the cultural products – textual and material – created in the CAM. ArmEn aims to trace shared features in the multi-lingual textual and artistic production of CAM and correlate them to the circulation of ideas and concepts, as well as to real-life interactions, between multiple groups, identifying the locations and agents of entanglements. The large but under-utilised body of Armenian sources to be explored together with those in Arabic, Georgian, Greek, Persian, Syriac, and Turkish, will illuminate cultural entanglements between Muslim and Christian Arabs, Byzantines, Syriac Christians, Georgians, Caucasian Albanians, Turko-Muslim dynasties, Kurds, Iranians, Western Europeans, and Mongols, that inhabited, conquered, or passed through and produced cultural goods in CAM. Evidence from manuscript illuminations and numismatics will provide a material cultural dimension to the analysis. ArmEn will create a trans-cultural vision of the CAM, bridging area studies into a unifying framework, bringing together various disciplinary approaches (philology, literary criticism, religious studies, art history, numismatics, etc.), to build a narrative synthesis in which the dynamics of cross-cultural entanglements in the CAM emerge in their spatial and temporal dimensions.

1 999 994 €

Start date: 2020-10-01, End date: 2025-09-30

Concise, massively ideological texts have long been perceived as constitutive of the development and transformation of opinion and policy in the public sphere. At least since the early Enlightenment, the pamphlet has been at the forefront of major philosophical, social, and political transformations, including processes of democratization and dedemocratization, colonization and decolonization, the universalization of civil and civic rights, the enforcement of political or territorial autonomy, and the critique of labor exploitation. Since the fall of the Berlin Wall, pamphleteering has reemerged as a vital transformative and polemical force in liberal Western societies, prompting often polarized discussions of contentious issues. By integrating philological, historical, and politological research perspectives, ArtsAutonomy will produce a first systematic, large-scale account of contemporary pamphleteering and shed new light on the perceived ongoing radicalization of political, cultural, and social ideals and discourses in contemporary Europe and the United States. We intend to achieve our epistemic goals by studying “pamphletary events”, i.e. events which unfold in the public sphere and which engage both a pamphletary text and interpretative competences widely distributed among the general reading public. ArtsAutonomy will produce several thematically organized case studies of pamphletary events, including analytic “slices” of evolving public opinion on pamphletary statements, as recorded in transcripts of public deliberations, open letters, online commentary, user and consumer feedback, and social media. Our multidisciplinary approach will provide a unique insight into the concrete current political agency of one of the oldest literary forms, as well as into the philological-interpretative competences upon which pamphletary events and their normalization are predicated.

1 229 665 €

Start date: 2020-03-01, End date: 2025-02-28

Astaxanthin is a carotenoid with a high commercial value. Its high anti-oxidant activity makes Astaxanthin being used as a food/feed supplements, in cosmetics, and in nutraceutics. Microalgae are the main primary sources of Astaxanthin, being produced at industrial level mainly by cultivation of the green alga Haematococcus pluvialis with high costs for cultivation and extraction, hindering its market. In the ERC-StG-SOLENALGAE project the investigation of the role of carotenoids in photoprotection in microalgae led to the development of an innovative platform for Astaxanthin production. Strains with high Astaxanthin accumulation were indeed obtained by metabolic engineering in the green alga Chlamydomonas reinhardtii (usually not accumulating Astaxanthin), producing up to 4 mg/L per day in non-optimized growth conditions. Astaxanthin production by bkt15 strain revealed unique advantages compared to other source of natural Astaxanthin: production of Astaxanthin in continuous, in a single cultivation step; high bio-accessibility for animal or human assimilation; easier extraction of astaxanthin even without costly cell pre-treatments; lower extraction costs and no contamination from oxidant molecules as chlorophylls during extraction process. These advantages lead to a potential increase in pure Astaxanthin productivity up to 16-fold higher than the current methods. ASTEASY PoC aims to the technological development of the new system, by optimizing the cultivation conditions and extraction processes of Astaxanthin from the bkt15 strain and validating the performances in 60 litres demonstrator units. We will also identify and protect the IP generated and analyse the certification needed for commercialization. A business plan will be drafted as a result of interactions with stakeholders and literature analysis, to define market size and trends, and consolidate the business model (Astaxanthin production through a dedicated spin-off vs licensing to Astaxanthin producers).

150 000 €

Start date: 2020-03-01, End date: 2021-08-31

The Sun and the surrounding heliosphere move through a low-density region in the Galaxy, which is filled with partially ionized gas and interstellar dust. While the Voyager 1 and 2 missions are currently exploring the heliosphere boundary regions that are shaped by both the Sun and by the Local Interstellar Medium (LISM), fundamental questions about our galactic neighbourhood remain unanswered: how is the structure and dynamics of the heliosphere, how does the heliosphere-LISM interaction work, and what is the nature of the LISM, including magnetic fields and contemporary interstellar dust composition, diversity, density and size distribution? In situ measurements of interstellar dust moving through the solar system provide unique ground truth information, but they have also been puzzling the community: they are not yet understood in the frame of dust dynamics simulations - related to the heliosphere properties. Also Voyager measurements at the heliosphere boundary kept surprising and challenging our views on the outer heliosphere to the very fundamental level. ASTRODUST will combine unique in situ interstellar dust observations in the solar system, with interstellar dust trajectory simulations that are coupled to a dynamic heliosphere, including its boundary regions and the ISM. ASTRODUST will build a synergy between two fields (heliosphere, dust) in order to answer fundamental questions about the dust and the heliosphere-LISM interaction. With ASTRODUST, we use a new way to explore and understand our local galactic neighbourhood. It also serves as an essential step towards understanding galaxy evolution (via the dust), how stars interact with their surroundings (astrospheres), and the history and future of the solar system on its continuous journey through the galaxy.

1 484 038 €

Start date: 2020-01-01, End date: 2024-12-31

Although Nakamoto’s original blockchain protocol has spurred significant innovation and financial interest in the last decade, its energy consumption becomes problematic. Besides, transaction latencies are prohibitively high and the system sustains a very low throughput. We have witnessed hundreds of alternative solutions in the last decade. Each seeks to reduce energy consumption, to obtain lower latency, or to improve throughput. All proposed alternatives, however, sacrifice either trustworthiness or efficiency. In retrospect, this is not surprising. All these solutions seek to solve a notoriously difficult problem: consensus. In short, the set of nodes in the network have to agree on the same position of a block in the chain, despite the possibility of malicious behaviour of some of the nodes, or network delays. The consensus problem has been the most studied problem in distributed computing, and many impossibility and lower bound results were established. These results translate into inherent trade-offs between trust and efficiency. In the context of our ERC AOC (Adversary-Oriented Computing) project (advanced grant), we worked on classifying distributed computing problems according to their hardness. While doing so, we revisited the issue of implementing a trustworthy payment system, i.e., the problem solved in Nakamoto’s paper. This led us to a very interesting discovery: Current blockchain protocols are tackling a problem, i.e., consensus, which is unnecessarily strong for their purpose of building a payment system. More specifically, we have shown that it is enough to solve a problem called secure causal broadcast to implement trust in any tokenized application. This is significantly simpler than consensus. We devised a generic asynchronous protocol to solve the secure causal broadcast problem, which we called AT2, Asynchronous Trustworthy Transactions, which we patented. The goal of this project is to pave the path to its commercialization.

150 000 €

Start date: 2019-10-01, End date: 2021-06-30

The marine ecosystem covers around 70% of the planet. Today, every single part of this vast ecosystem is affected by at least one anthropogenic driver of change. This fact should cause us to pause and think: such a huge space, yet habitat and species loss are occurring at an unprecedented rate. The marine ecosystem provides us with a wealth of services and has an economic value exceeding 20 trillion US Dollars. In addition, the marine ecosystem is considered crucial for our sustainable future and is often regarded as the “next economic frontier”. However, despite its importance for humankind, the marine ecosystem is significantly underrepresented in sustainability research. We currently have no holistic approach to quantify the impacts caused by a large number of human pressures in the marine ecosystem. A powerful tool for identifying such impacts is life cycle assessment (LCA). LCA is the best available tool to assess potential environmental impacts of products and processes in a comprehensive way. However, methods have never been properly developed for including marine impacts in LCA results. I will contribute to closing this substantial research gap by developing novel models for quantifying impacts on ecosystem service losses (“whales”), as well as impacts of marine plastic debris (“waste”) and of marine invasive species (“sea walnuts”) within the LCA framework. These models will be developed based on impacts on species richness and ecosystem service potential. Including ecosystem services will be a paradigm extension and a substantial advancement for the LCA framework. All models will be tested in an overarching case study. Currently we are unable to determine whether planned marine activities and processes are sustainable. By developing these models, we will be able to do so with a holistic perspective. This is of unprecedented importance, if we want to manage this vital ecosystem in a sustainable way and preserve it for future generations.

1 500 000 €

Start date: 2020-04-01, End date: 2025-03-31

Interfaces in oxide materials offer amazing opportunities for fundamental and applied research, giving a new dimension to functional properties, such as magnetism, multiferroicity and superconductivity. Ferroelectric domain walls recently emerged as a new type of interface, where the dynamic characteristics of ferroelectricity introduce the element of spatial mobility, allowing for the real-time adjustment of position, density and orientation of the walls. This mobility adds an additional degree of flexibility that enables domain walls to take an active role in future devices and hold great potential as functional 2D systems for electronics. Up to now, application concepts rely on injecting and deleting domain walls in micrometer-size devices to control electric conductivity. While this approach achieves a step beyond conventional interfaces by utilizing the wall mobility, it does not break the mould of classical device architectures. Completely new strategies are required to functionalize the versatile electronic properties and atomic-scale feature size of ferroelectric domain walls. ATRONICS will establish a new conceptual approach for developing domain-wall-based technology. At the length scale of only a few atoms, we will use individual walls in improper ferroelectrics to emulate key electronic components such as diodes, transistors and logic gates. Crucially, as the functionality of the components is intrinsic to the domain walls, the walls themselves are the devices, instead of the previous approach of writing and erasing domain walls within a much larger classical device architecture. Beyond demonstrating individual devices, we will integrate multiple domain-wall devices, and develop quasi-2D circuitry and networks with a higher order of complexity then is currently achievable. ATRONICS will represent a major advancement in 2D functional materials for future technologies and play an essential role in the transition from nano- to atomic-scale electronics.

1 845 338 €

Start date: 2020-09-01, End date: 2025-08-31

Strong-field-driven electric currents in condensed-matter systems open new frontiers in manipulating electronic and optical properties on petahertz frequency scales. In this regime, new challenges arise as the role of the band structure and the quantum nature of ultrafast electron-hole dynamics have yet to be resolved. While petahertz spectroscopy and control of condensed-matter systems holds great potential, revealing the underlying attosecond (1 attosecond – 10(-18) second) dynamics of electrons in solids is still in its infancy. The proposed research aims at the development of a state-of-the-art attosecond metrology scheme that integrates the concept of holography with attosecond gating. Attosecond-gated holography will provide direct insight into the instantaneous evolution of the complex quantum wavefunctions in solid-state systems. This scheme will enable us to follow the electron-hole wavepacket evolution during ultrafast band structure deformation, probing a range of fundamental processes – from sub-cycle phase transitions to ultrafast dynamics in correlated systems. In ATTO-GRAM, we will establish attosecond-gated holography and then apply it to study field-induced transient band structures, resolve electron-hole dynamics during lattice deformation and reveal attosecond phenomena in strongly correlated systems. Integrating state-of-the-art experimental schemes, supported by advanced theoretical analysis, will lead to the discoveries of new phenomena previously deemed inaccessible. The impact of the proposed research reaches beyond attosecond metrology – opening new routes in the establishment of compact solid-state extreme ultraviolet sources, petahertz electronics and optically induced metamaterials.

2 000 000 €

Start date: 2020-01-01, End date: 2024-12-31

Speed and performances of contemporary digital electronics are limited by the available device architectures and heat dissipation. Two-dimensional (2D) materials are emerging as one of the main candidates for designing new structures capable to overcome the current device limitations and foster the establishment of the electronics of the future. Due to the electron confinement in two directions, they are characterised by exotic physical, electronic and chemical properties, which are neither fully investigated nor understood. In particular, the lack of suitable tools hinders the possibility to study the ultrafast processes unfolding during light-matter interaction. Nevertheless, a clear understanding is required in order to leverage the unique properties of 2D materials. AuDACE aims to enter this unexplored region and investigate ultrafast electron, exciton and spin dynamics happening in advanced materials on time scales below few femtoseconds with unprecedented and ground-breaking possible outcome. To reach this ambitious goal AuDACE will go beyond the state of the art and develop an innovative pump-probe beamline for transient absorption and reflectivity measurements based on arbitrarily polarised attosecond pulses in a two-foci geometry. Once the experimental techniques are established, my team and I will concentrate on ultrafast exciton dynamics in monolayer transition metal dichalcogenides (ML-TMDCs). In the final phase, AuDACE will focus on a new class of materials such as ferromagnetic ML-TMDCs to investigate the elusive physical mechanism responsible for ultrafast spin and magnetic dynamics. For the first time, a comprehensive investigation of these phenomena will become feasible on these little studied time scales. Due to the wide spectrum of relevant applications for 2D materials, I expect the outcome of AuDACE to have a crucial impact on the development of many key technological areas like optoelectronics, spintronics, valleytronics and photovoltaics.

1 466 250 €

Start date: 2020-02-01, End date: 2025-01-31

Weapons systems with an increasing number of autonomous features are emerging as revolutionary technologies of war. In particular, this concerns systems with autonomy in their critical functions that relate to selecting and engaging targets without human input. This weaponisation of Artificial Intelligence (AI) signals the looming absence of meaningful human control in warfare, which has become a central focus of the debate on autonomous weapons systems (AWS). Here, states either seek to introduce new norms governing AWS or to leave the field open in order to increase their room of manoeuvre. These uncertainties make monitoring to what extent AWS will shape and transform international norms governing the use of force a matter of great importance. But existing International Relations research on norms despite producing excellent critical work does not yet enable us to understand the dynamics of this vital process because it does not capture adequately how norms emerge and develop. The state of the art conceptually connects norms predominantly to international law and limits attention to how norms emerge in deliberative international forums. Instead, the AUTONORMS project will develop a new ground-breaking theoretical approach that allows us to study how norms, understood as standards of appropriateness, manifest and change in practices. Taking this bottom-up perspective, we will monitor norm emergence and change across four contexts of practices (military, transnational political, dual-use, and popular imagination) in four countries (USA, China, Japan, Russia). This flexible portrayal allows us to adequately understand how norms related to AWS will develop, as well as considering the impact such emerging norms have on the current international security order of which norms are constitutive building blocs. The project thus provides an innovative analytical model for studying uncertain processes of technological innovation associated with the AI revolution.

1 499 759 €

Start date: 2020-08-01, End date: 2025-07-31

The inappropriate use of antibiotics has rapidly accelerated antibiotic resistance evolution in pathogens, rendering several existing antibiotics ineffective. However, many pharmaceutical companies have discontinued their antibiotic research programs. This is foremost due to the rapid spread of multi-drug resistant bacteria, which makes the commercial success of new antimicrobial drugs unpredictable. Antibiotic developers do not have a toolset to appropriately test antibiotic candidates for resistance evolution. Specifically, in the early phase of drug development, researchers typically identify numerous lead molecules with antimicrobial activities. It would be imperative to estimate the rate of resistance evolution at this early stage of development to all lead candidates in order to choose those that are the least prone to resistance evolution. The applicant and his team developed a technology, they term DIvERGE. It enables the exploration of resistance in a manner that is more comprehensive and effective than any other currently used approach. In a nutshell, DIvERGE finds resistance mutations in antibiotic resistance genes at an unprecedentedly comprehensive manner . DIvERGE offers a unique opportunity for pharmaceutical companies to identify antimicrobial agents with potentially longer clinical efficacy at an early stage of drug development. Thus, the goal is simple and bold – to identify antibiotics that are less prone to resistance development. Here the team aims to commercialise the technology.

150 000 €

Start date: 2019-11-01, End date: 2021-10-31

This proposal aims at understanding how B cell specificity and immunodominance shape primary and secondary humoral responses to influenza A virus. Influenza A virus is a relevant human pathogen causing a considerable yearly death toll and economic burden to society. Immunodominance is a major driving force of adaptive immunity and defines the hierarchical recognition of epitopes on the same antigen. Previous studies analysing B cell dynamics in primary and secondary responses have been mainly focusing on simple antigens and competition between B cell clones of the same family. Investigation using complex antigens and examining interclonal competition are surprisingly scarce. Influenza hemagglutinin (HA) is a prime candidate to study immunodominance in B cells. I have generated a set of mutant viruses that will allow for an unprecedented investigation into immunodominance and B cell interclonal competition in primary and secondary responses. These viruses can be used to isolate and enumerate antibody and B cells specific for different epitopes on the same complex antigen (HA). I will use these unique tools in combination with state-of-the-art immunological methods, multi-colour flow cytometry and single cells RNA sequencing paired with B cell receptor sequencing to gain fundamental insights into B cell regulation and anti-viral humoral responses. I will i) study the link between B cell receptor characteristics, specificity and B cell fate decisions in primary responses, ii) characterize the relative contribution of pre-existing B cells, serum antibodies and CD4 T cells for immunodominance of secondary responses, iii) define immunodominance in human individuals, repeatedly exposed to influenza virus. I expect this project to critically improve our understanding of basic B cell biology with the long-term benefit of improving current vaccination against variable viral pathogens.

1 481 697 €

Start date: 2019-12-01, End date: 2024-11-30