ERC FUNDED PROJECTS

Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.

1 100 000 €

Start date: 2008-09-01, End date: 2014-04-30

I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.

2 311 696 €

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

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

1 489 823 €

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

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

1 966 429 €

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

Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism. The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression. I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen. The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.

1 498 175 €

Start date: 2017-04-01, End date: 2022-03-31

Topological materials have developed rapidly in recent years, with my previous ERC-AG project 3-TOP playing a major role in this development. While so far no bulk topological superconductor has been unambiguously demonstrated, their properties can be studied in a very flexible manner by inducing superconductivity through the proximity effect into the surface or edge states of a topological insulator. In 4-TOPS we will explore the possibilities of this approach in full, and conduct a thorough study of induced superconductivity in both two and three dimensional HgTe based topological insulators. The 4 avenues we will follow are: -SQUID based devices to investigate full phase dependent spectroscopy of the gapless Andreev bound state by studying their Josephson radiation and current-phase relationships. -Experiments aimed at providing unambiguous proof of localized Majorana states in TI junctions by studying tunnelling transport into such states. -Attempts to induce superconductivity in Quantum Hall states with the aim of creating a chiral topological superconductor. These chiral superconductors host Majorana fermions at their edges, which, at least in the case of a single QH edge mode, follow non-Abelian statistics and are therefore promising for explorations in topological quantum computing. -Studies of induced superconductivity in Weyl semimetals, a completely unexplored state of matter. Taken together, these four sets of experiments will greatly enhance our understanding of topological superconductivity, which is not only a subject of great academic interest as it constitutes the study of new phases of matter, but also has potential application in the field of quantum information processing.

2 497 567 €

Start date: 2017-06-01, End date: 2022-05-31

The focus of this project is the development of algorithms that allow one to capture and analyse dynamic events taking place in the real world. For this, we intend to develop smart camera networks that can perform a multitude of observation tasks, ranging from surveillance and tracking to high-fidelity, immersive reconstructions of important dynamic events (i.e. 4D videos). There are many fundamental questions in computer vision associated with these problems. Can the geometric, topologic and photometric properties of the camera network be obtained from live images? What is changing about the environment in which the network is embedded? How much information can be obtained from dynamic events that are observed by the network? What if the camera network consists of a random collection of sensors that happened to observe a particular event (think hand-held cell phone cameras)? Do we need synchronization? Those questions become even more challenging if one considers active camera networks that can adapt to the vision task at hand. How should resources be prioritized for different tasks? Can we derive optimal strategies to control camera parameters such as pan, tilt and zoom, trade-off resolution, frame-rate and bandwidth? More fundamentally, seeing cameras as points that sample incoming light rays and camera networks as a distributed sensor, how does one decide which rays should be sampled? Many of those issues are particularly interesting when we consider time-varying events. Both spatial and temporal resolution are important and heterogeneous frame-rates and resolution can offer advantages. Prior knowledge or information obtained from earlier samples can be used to restrict the possible range of solutions (e.g. smoothness assumption and motion prediction). My goal is to obtain fundamental answers to many of those question based on thorough theoretical analysis combined with practical algorithms that are proven on real applications.

1 757 422 €

Start date: 2008-08-01, End date: 2013-11-30

Although we have extensive knowledge of many important processes in cell biology, including information on many of the molecules involved and the physical interactions among them, we still do not understand most of the dynamical features that are the essence of living systems. This is particularly true for the actin cytoskeleton, a major component of the internal architecture of eukaryotic cells. In living cells, actin networks constantly assemble and disassemble filaments while maintaining an apparent stable structure, suggesting a perfect balance between the two processes. Such behaviors are called “dynamic steady states”. They confer upon actin networks a high degree of plasticity allowing them to adapt in response to external changes and enable cells to adjust to their environments. Despite their fundamental importance in the regulation of cell physiology, the basic mechanisms that control the coordinated dynamics of co-existing actin networks are poorly understood. In the AAA project, first, we will characterize the parameters that allow the coupling among co-existing actin networks at steady state. In vitro reconstituted systems will be used to control the actin nucleation patterns, the closed volume of the reaction chamber and the physical interaction of the networks. We hope to unravel the mechanism allowing the global coherence of a dynamic actin cytoskeleton. Second, we will use our unique capacity to perform dynamic micropatterning, to add or remove actin nucleation sites in real time, in order to investigate the ability of dynamic networks to adapt to changes and the role of coupled network dynamics in this emergent property. In this part, in vitro experiments will be complemented by the analysis of actin network remodeling in living cells. In the end, our project will provide a comprehensive understanding of how the adaptive response of the cytoskeleton derives from the complex interplay between its biochemical, structural and mechanical properties.

2 349 898 €

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

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

150 000 €

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

The centriole is the largest evolutionary conserved macromolecular structure responsible for building centrosomes and cilia or flagella in many eukaryotes. Centrioles are critical for the proper execution of important biological processes ranging from cell division to cell signaling. Moreover, centriolar defects have been associated to several human pathologies including ciliopathies and cancer. This state of facts emphasizes the importance of understanding centriole biogenesis. The study of centriole formation is a deep-rooted question, however our current knowledge on its molecular organization at high resolution remains fragmented and limited. In particular, exquisite details of the overall molecular architecture of the human centriole and in particular of its central core region are lacking to understand the basis of centriole organization and function. Resolving this important question represents a challenge that needs to be undertaken and will undoubtedly lead to groundbreaking advances. Another important question to tackle next is to develop innovative methods to enable the nanometric molecular mapping of centriolar proteins within distinct architectural elements of the centriole. This missing information will be key to unravel the molecular mechanisms behind centriolar organization. This research proposal aims at building a cartography of the human centriole by elucidating its molecular composition and architecture. To this end, we will combine the use of innovative and multidisciplinary techniques encompassing spatial proteomics, cryo-electron tomography, state-of-the-art microscopy and in vitro assays and to achieve a comprehensive molecular and structural view of the human centriole. All together, we expect that these advances will help understand basic principles underlying centriole and cilia formation as well as might have further relevance for human health.

1 498 965 €

Start date: 2017-01-01, End date: 2021-12-31

Since completion of the first human genome sequence, the demand for cheaper and faster sequencing methods has increased enormously. This need has driven the development of second-generation sequencing methods, or next-generation sequencing (also known as NGS or high throughput sequencing). The creation of these platforms has made sequencing accessible to more laboratories, rapidly increasing the volume of research, including clinical diagnostics and its use in directing treatment (precision medicine). The applications of NGS are also allowing rapid advances in clinically related fields such as public health and epidemiology. Such developments illustrate why sequencing is now the fastest-growing area in genomics (+23% p.a.). The activity is said to be worth $2.5B this year, and poised to reach ~$9B by 2020. In any workflow, prior to the sequencing reactions, a number of pre-sequencing steps are required, including the fragmentation of the DNA into smaller sizes for processing, size selection, library preparation and target enrichment. This proposal is specifically concerned with this latter area, namely DNA fragmentation – now widely acknowledged across the industry as being the most important technological bottleneck in the pre-sequencing workflow. Our new method for DNA fragmentation – involving using surface acoustic waves will enable sample preparation from lower sample volumes using lower powers. It also has the potential to allow the seamless integration of fragmentation into sequencing instrumentation, opening up the possibility of “sample to answer” diagnostics. In the near term this will enable the implementation of sample preparation pre-sequencing steps within the NGS instruments. In the longer term, our techniques will also enable us to develop methods for field-based DNA sequencing – as may be required for determining “microbial resistance” and informing the treatment of infectious disease in the face of the emergence of drug resistance.

149 995 €

Start date: 2017-05-01, End date: 2018-10-31

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

150 000 €

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

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

150 000 €

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

Obesity associated disorders such as T2D, hypertension and CVD, commonly referred to as the “metabolic syndrome”, are prevalent diseases of industrialized societies. Deranged adipose tissue proliferation and differentiation contribute significantly to the development of these metabolic disorders. Comparatively little however is known, about how these processes influence the development of metabolic disorders. Using a multidisciplinary approach, I plan to elucidate molecular mechanisms underlying the altered adipocyte differentiation and maturation in different models of obesity associated metabolic disorders. Special emphasis will be given to the analysis of gene expression, postranslational modifications and lipid molecular species composition. To achieve this goal, I am establishing several novel methods to isolate pure primary preadipocytes including a new animal model that will allow me to monitor preadipocytes, in vivo and track their cellular fate in the context of a complete organism. These systems will allow, for the first time to study preadipocyte biology, in an in vivo setting. By monitoring preadipocyte differentiation in vivo, I will also be able to answer the key questions regarding the development of preadipocytes and examine signals that induce or inhibit their differentiation. Using transplantation techniques, I will elucidate the genetic and environmental contributions to the progression of obesity and its associated metabolic disorders. Furthermore, these studies will integrate a lipidomics approach to systematically analyze lipid molecular species composition in different models of metabolic disorders. My studies will provide new insights into the mechanisms and dynamics underlying adipocyte differentiation and maturation, and relate them to metabolic disorders. Detailed knowledge of these mechanisms will facilitate development of novel therapeutic approaches for the treatment of obesity and associated metabolic disorders.

1 607 105 €

Start date: 2008-07-01, End date: 2013-06-30

New insight into ever smaller microscopic units of matter as well as in ever faster evolving chemical, physical or atomic processes pushes the frontiers in many fields in science. Pump/probe experiments turned out to be the most direct approach to time-domain investigations of fast-evolving microscopic processes. Accessing atomic and molecular inner-shell processes directly in the time-domain requires a combination of short wavelengths in the few hundred eV range and sub-femtosecond pulse duration. The concept of light-field-controlled XUV photoemission employs an XUV pulse achieved by High-order Harmonic Generation (HHG) as a pump and the light pulse as a probe or vice versa. The basic prerequisite, namely the generation and measurement of isolated sub-femtosecond XUV pulses synchronized to a strong few-cycle light pulse with attosecond precision, opens up a route to time-resolved inner-shell atomic and molecular spectroscopy with present day sources. Studies of attosecond electronic motion (1 as = 10-18 s) in solids and on surfaces and interfaces have until now remained out of reach. The unprecedented time resolution of the aforementioned technique will enable for the first time monitoring of sub-fs dynamics of such systems in the time domain. These dynamics – of electronic excitation, relaxation, and wave packet motion – are of broad scientific interest and pertinent to the development of many modern technologies including semiconductor and molecular electronics, optoelectronics, information processing, photovoltaics, and optical nano-structuring. The purpose of this project is to investigate phenomena like the temporal evolution of direct photoemission, interference effects in resonant photoemission, fast adsorbate-substrate charge transfer, and electronic dynamics in supramolecular assemblies, in a series of experiments in order to overcome the temporal limits of measurements in solid state physics and to better understand processes in microcosm.

1 296 000 €

Start date: 2008-10-01, End date: 2013-09-30

Active Matter systems, such as self-propelled colloids, violate time-reversal symmetry by producing entropy locally, typically converting fuel into mechanical motion at the particle scale. Other driven systems instead produce entropy because of global forcing by external fields, or boundary conditions that impose macroscopic fluxes (such as the momentum flux across a fluid sheared between moving parallel walls). Nonequilibrium statistical physics (NeSP) is the basic toolbox for both classes of system. In recent years, much progress in NeSP has stemmed from bottom-up work on driven systems. This has provided a number of exactly solved benchmark models, and extended approximation techniques to address driven non-ergodic systems, such as sheared glasses. Meanwhile, work on fluctuation theorems and stochastic thermodynamics have created profound, model-independent insights into dynamics far from equilibrium. More recently, the field of Active Matter has moved forward rapidly, leaving in its wake a series of generic and profound NeSP questions that now need answers: When is time-reversal symmetry, broken at the microscale, restored by coarse-graining? If it is restored, is an effective thermodynamic description is possible? How different is an active system's behaviour from a globally forced one? ADSNeSP aims to distil from recent Active Matter research such fundamental questions; answer them first in the context of specific models and second in more general terms; and then, using the tools and insights gained, shed new light on longstanding problems in the wider class of driven systems. I believe these new tools and insights will be substantial, because local activity takes systems far from equilibrium in a conceptually distinct direction from most types of global driving. By focusing on general principles and on simple models of activity, I seek to create a new vantage point that can inform, and potentially transform, wider areas of statistical physics.

2 043 630 €

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

In a typical learning problem one tries to approximate an unknown function by a function from a given class using random data, sampled according to an unknown measure. In this project we will be interested in parameters that govern the complexity of a learning problem. It turns out that this complexity is determined by the geometry of certain sets in high dimension that are connected to the given class (random coordinate projections of the class). Thus, one has to understand the structure of these sets as a function of the dimension - which is given by the cardinality of the random sample. The resulting analysis leads to many theoretical questions in Asymptotic Geometric Analysis, Probability (most notably, Empirical Processes Theory) and Combinatorics, which are of independent interest beyond the application to Learning Theory. Our main goal is to describe the role of various complexity parameters involved in a learning problem, to analyze the connections between them and to investigate the way they determine the geometry of the relevant high dimensional sets. Some of the questions we intend to tackle are well known open problems and making progress towards their solution will have a significant theoretical impact. Moreover, this project should lead to a more complete theory of learning and is likely to have some practical impact, for example, in the design of more efficient learning algorithms.

750 000 €

Start date: 2009-03-01, End date: 2014-02-28

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

2 499 595 €

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

Taking inspiration from natural carriers, such as viruses, a new technology has been developed in our laboratories part of an ongoing ERC starting grant project, Molecular Engineering of Virus-like Carriers (MEViC). We created synthetic viruses using polymers and thus safer materials. They are able of delivering high payload of specific drugs into cells with no detrimental effect. While testing for anticancer therapies, we identified a synthetic virus capable of targeting almost exclusively macrophages. We performed preliminary work showing that this can be successfully applied to deliver antibiotics to rid of intracellular pathogens. This has now open a completely new possibility whereas we can expand our technology for the treatment of several infections as well as to contribute to the ongoing efforts in tackling antibiotic resistance.

149 062 €

Start date: 2017-07-01, End date: 2018-12-31

This project will develop the principles required to enable bond-modifying redox catalysis based on aluminium by preparing and studying new Al(I) compounds capable of reversible oxidative addition. Catalytic processes are involved in the synthesis of 75 % of all industrially produced chemicals, but most catalysts involved are based on precious metals such as rhodium, palladium or platinum. These metals are expensive and their supply limited and unstable; there is a significant need to develop the chemistry of non-precious metals as alternatives. On toxicity and abundance alone, aluminium is an attractive candidate. Furthermore, recent work, including in our group, has demonstrated that Al(I) compounds can perform a key step in catalytic cycles - the oxidative addition of E-H bonds. In order to realise the significant potential of Al(I) for transition-metal style catalysis we urgently need to: - establish the principles governing oxidative addition and reductive elimination reactivity in aluminium systems. - know how the reactivity of Al(I) compounds can be controlled by varying properties of ligand frameworks. - understand the onward reactivity of oxidative addition products of Al(I) to enable applications in catalysis. In this project we will: - Study mechanisms of oxidative addition and reductive elimination of a range of synthetically relevant bonds at Al(I) centres, establishing the principles governing this fundamental reactivity. - Develop new ligand frameworks to support of Al(I) centres and evaluate the effect of the ligand on oxidative addition/reductive elimination at Al centres. - Investigate methods for Al-mediated functionalisation of organic compounds by exploring the reactivity of E-H oxidative addition products with unsaturated organic compounds.

1 493 679 €

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

Mathematical proofs have always been prone to error. Today, proofs can be hundreds of pages long and combine results from many specialisms, making them almost impossible to check. One solution is to deploy modern verification technology. Interactive theorem provers have demonstrated their potential as vehicles for formalising mathematics through achievements such as the verification of the Kepler Conjecture. Proofs done using such tools reach a high standard of correctness. However, existing theorem provers are unsuitable for mathematics. Their formal proofs are unreadable. They struggle to do simple tasks, such as evaluating limits. They lack much basic mathematics, and the material they do have is difficult to locate and apply. ALEXANDRIA will create a proof development environment attractive to working mathematicians, utilising the best technology available across computer science. Its focus will be the management and use of large-scale mathematical knowledge, both theorems and algorithms. The project will employ mathematicians to investigate the formalisation of mathematics in practice. Our already substantial formalised libraries will serve as the starting point. They will be extended and annotated to support sophisticated searches. Techniques will be borrowed from machine learning, information retrieval and natural language processing. Algorithms will be treated similarly: ALEXANDRIA will help users find and invoke the proof methods and algorithms appropriate for the task. ALEXANDRIA will provide (1) comprehensive formal mathematical libraries; (2) search within libraries, and the mining of libraries for proof patterns; (3) automated support for the construction of large formal proofs; (4) sound and practical computer algebra tools. ALEXANDRIA will be based on legible structured proofs. Formal proofs should be not mere code, but a machine-checkable form of communication between mathematicians.

2 430 140 €

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

Osteoarthritis (OA) is a common joint disease affecting over 40 million Europeans. Most common consequences of OA are pain, disability and social isolation. What is alarming, the number of patients will increase 50% in developed countries during the next 20 years. Moreover, the economic costs of OA are considerable since 1) direct healthcare (hospital admissions, medical examinations, drug therapy, etc.) and 2) productivity costs due to reduced performance while at work and absence from work have been estimated to be between 1% and 2.5% of the gross domestic product (GDP) in Western countries. We have developed an algorithm that is able to predict the progression of OA for overweight subjects while healthy subjects do not develop OA. When employed in clinical use, preventive and personalised treatments can be started before clinically significant symptoms are observed. This marks a major breakthrough in improving the life quality of OA patients and patients prone to OA. Our discovery will directly lead to longer working careers and lesser absence from work, and will result subsequently increased productivity. Moreover, the patients are expected to live longer due to reduced disability and social isolation. Moreover, the discovery provides economic long-term relief for the health care system, which is burdened by increasing geriatric population and stringent economic environment. With our tool, as an example, by eliminating 25% of medical examinations annually due to overweight or obesity in Finland (150.000 patients), we estimate to decrease annual direct costs by 140M€ and indirect costs by 185M€. In the PoC project we will carry out technical proof-of-concept and perform pre-commercialisation actions to shorten the time to market. The ultimate goal after the project is to develop our innovation towards a software product, aiding the OA diagnostics in hospitals and having commercialisation potential amongst medical device companies.

150 000 €

Start date: 2018-01-01, End date: 2019-06-30

Recurrent neural networks (RNNs) are general parallel-sequential computers. Some learn their programs or weights. Our supervised Long Short-Term Memory (LSTM) RNNs were the first to win pattern recognition contests, and recently enabled best known results in speech and handwriting recognition, machine translation, etc. They are now available to billions of users through the world's most valuable public companies including Google and Apple. Nevertheless, in lots of real-world tasks RNNs do not yet live up to their full potential. Although universal in theory, in practice they fail to learn important types of algorithms. This ERC project will go far beyond today's best RNNs through novel RNN-like systems that address some of the biggest open RNN problems and hottest RNN research topics: (1) How can RNNs learn to control (through internal spotlights of attention) separate large short-memory structures such as sub-networks with fast weights, to improve performance on many natural short-term memory-intensive tasks which are currently hard to learn by RNNs, such as answering detailed questions on recently observed videos? (2) How can such RNN-like systems metalearn entire learning algorithms that outperform the original learning algorithms? (3) How to achieve efficient transfer learning from one RNN-learned set of problem-solving programs to new RNN programs solving new tasks? In other words, how can one RNN-like system actively learn to exploit algorithmic information contained in the programs running on another? We will test our systems existing benchmarks, and create new, more challenging multi-task benchmarks. This will be supported by a rather cheap, GPU-based mini-brain for implementing large RNNs.

2 500 000 €

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

The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences. My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.

1 222 329 €

Start date: 2016-12-01, End date: 2021-11-30

In most European countries social insurance programs, like welfare, unemployment insurance and disability insurance are characterized by low reemployment rates. Therefore, governments spend huge amounts of money on active labour market programs, which should help individuals in finding work. Recent surveys indicate that programs which aim at intensifying job search behaviour are much more effective than schooling programs for improving human capital. A second conclusion from these surveys is that despite the size of the spendings on these programs, evidence on its effectiveness is limited. This research proposal aims at developing an economic framework that will be used to evaluate the effectiveness of popular programs like offering reemployment bonuses, fraud detection, workfare and job search monitoring. The main innovation is that I will combine economic theory with recently developed econometric techniques and detailed administrative data sets, which have not been explored before. While most of the literature only focuses on short-term outcomes, the available data allow me to also consider the long-term effectiveness of programs. The key advantage of an economic model is that I can compare the effectiveness of the different programs, consider modifications of programs and combinations of programs. Furthermore, using an economic model I can construct profiling measures to improve the targeting of programs to subsamples of the population. This is particularly relevant if the effectiveness of programs differs between individuals or depends on the moment in time the program is offered. Therefore, the results from this research will not only be of scientific interest, but will also be of great value to policymakers.

550 000 €

Start date: 2008-07-01, End date: 2013-06-30

This interdisciplinary project investigates the transformation of Shii Islam in the Middle East and Europe since the 1950s. The project examines the formation of modern Shii communal identities and the role Shii clerical authorities and their transnational networks have played in their religio-political mobilisation. The volatile situation post-Arab Spring, the rise of militant movements such as ISIS and the sectarianisation of geopolitical conflicts in the Middle East have intensified efforts to forge distinct Shii communal identities and to conceive Shii Muslims as part of an alternative umma (Islamic community). The project focusses on Iran, Iraq and significant but unexplored diasporic links to Syria, Kuwait and Britain. In response to the rise of modern nation-states in the Middle East, Shii clerical authorities resorted to a wide range of activities: (a) articulating intellectual responses to the ideologies underpinning modern Middle Eastern nation-states, (b) forming political parties and other platforms of socio-political activism and (c) using various forms of cultural production by systematising and promoting Shii ritual practices and utilising visual art, poetry and new media. The project yields a perspectival shift on the factors that led to Shii communal mobilisation by: - Analysing unacknowledged intellectual responses of Shii clerical authorities to the secular or sectarian ideologies of post-colonial nation-states and to the current sectarianisation of geopolitics in the Middle East. - Emphasising the central role of diasporic networks in the Middle East and Europe in mobilising Shii communities and in influencing discourses and agendas of clerical authorities based in Iraq and Iran. - Exploring new modes of cultural production in the form of a modern Shii aesthetics articulated in ritual practices, visual art, poetry and new media and thus creating a more holistic narrative on Shii religio-political mobilisation.

1 952 374 €

Start date: 2018-01-01, End date: 2022-12-31

"When I asked my seven-year-old daughter ""Who is the boy in your class who was also new in school last year, like you?"", she instantly replied ""Daniel"", using the descriptive content in my utterance to identify an entity in the real world and refer to it. The ability to use language to refer to reality is crucial for humans, and yet it is very difficult to model. AMORE breaks new ground in Computational Linguistics, Linguistics, and Artificial Intelligence by developing a model of linguistic reference to entities implemented as a computational system that can learn its own representations from data. This interdisciplinary project builds on two complementary semantic traditions: 1) Formal semantics, a symbolic approach that can delimit and track linguistic referents, but does not adequately match them with the descriptive content of linguistic expressions; 2) Distributional semantics, which can handle descriptive content but does not associate it to individuated referents. AMORE synthesizes the two approaches into a unified, scalable model of reference that operates with individuated referents and links them to referential expressions characterized by rich descriptive content. The model is a distributed (neural network) version of a formal semantic framework that is furthermore able to integrate perceptual (visual) and linguistic information about entities. We test it extensively in referential tasks that require matching noun phrases (“the Medicine student”, “the white cat”) with entity representations extracted from text and images. AMORE advances our scientific understanding of language and its computational modeling, and contributes to the far-reaching debate between symbolic and distributed approaches to cognition with an integrative proposal. I am in a privileged position to carry out this integration, since I have contributed top research in both distributional and formal semantics. "

1 499 805 €

Start date: 2017-02-01, End date: 2022-01-31

This project focuses on developing quantum field theory methods and applying them to the phenomenology of elementary particles. At the Large Hadron Collider (LHC) our current best theoretical understanding of particle physics is being tested against experiment by measuring e.g. properties of the recently discovered Higgs boson. With run two of the LHC, currently underway, the experimental accuracy will further increase. Theoretical predictions matching the latter are urgently needed. Obtaining these requires extremely difficult calculations of scattering amplitudes and cross sections in quantum field theory, including calculations to correctly describe large contributions due to long-distance physics in the latter. Major obstacles in such computations are the large number of Feynman diagrams that are difficult to handle, even with the help of modern computers, and the computation of Feynman loop integrals. To address these issues, we will develop innovative methods that are inspired by new structures found in supersymmetric field theories. We will extend the scope of the differential equations method for computing Feynman integrals, and apply it to scattering processes that are needed for phenomenology, but too complicated to analyze using current methods. Our results will help measure fundamental parameters of Nature, such as, for example, couplings of the Higgs boson, with unprecedented precision. Moreover, by accurately predicting backgrounds from known physics, our results will also be invaluable for searches of new particles.

2 000 000 €

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

Normal placental angiogenesis is critical for embryonic survival and development. Epigenetic modifications, such as methylation of CpG islands, regulate the expression and imprinting of genes. Epigenetic abnormalities have been observed in embryos from assisted reproductive technologies (ART), which could explain the poor placental vascularisation, embryonic/fetal death, and altered fetal growth in these pregnancies. Both cloned (somatic cell nuclear transfer, or SNCT) and monoparental (parthogenotes, only maternal genes; androgenotes, only paternal genes) embryos provide important models for studying defects in expression and methylation status/imprinting of genes regulating placental function. Our hypothesis is that placental vascular development is compromised during early pregnancy in embryos from ART, in part due to altered expression or imprinting/methylation status of specific genes regulating placental angiogenesis. We will evaluate fetal growth, placental vascular growth, and expression and epigenetic status of genes regulating placental angiogenesis during early pregnancy in 3 Specific Aims: (1) after natural mating; (2) after transfer of biparental embryos from in vitro fertilization, and SCNT; and (3) after transfer of parthenogenetic or androgenetic embryos. These studies will therefore contribute substantially to our understanding of the regulation of placental development and vascularisation during early pregnancy, and could pinpoint the mechanism contributing to embryonic loss and developmental abnormalities in foetuses from ART. Any or all of these observations will contribute to our understanding of and also our ability to successfully employ ART, which are becoming very wide spread and important in human medicine as well as in animal production.

363 600 €

Start date: 2008-10-01, End date: 2012-06-30

ANTS aims to prove the viability of a novel thermal microsensor, with highly improved thermal, temporal and spatial resolution, to be the basis of a breakthrough micro/nano-calorimeter. The resulting device shall quantify binding rates and enthalpy/entropy changes in interactions of biological interest in a much more accurate and straightforward manner than available techniques. Consequently, ANTS-microcalorimeter will facilitate enormously drug discovery and development of biomedical products and technologies. We propose to exploit the large Nernst effect in ferromagnetic conductors for electrical sensing of temperature gradients with exceptional sensitivity. The active sensing elements are composed of a single material, thus offering important advantages for miniaturization over conventional micro-calorimetry, based on diverse Peltier modules, whereas easy to fabricate by standard, scalable deposition and photolithographic methods. Standard microcalorimeter configuration can also be maintained in the novel device, which is convenient to ensure compatibility and foster adoption by users and manufacturers.

149 250 €

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

One’s ability to remember visual material such as objects, faces, and spatial locations over a short period of time declines with age. The proposed research will examine whether these deficits are explained by a reduction in visual working memory (VWM) capacity, or an impairment in one’s ability to maintain, or ‘bind’ appropriate associations among pieces of related information. In this project successful binding is operationally defined as the proper recall or recognition of objects that are defined by the conjunction of multiple visual features. While tests of long-term memory have demonstrated that, despite preserved memory for isolated features, older adults have more difficulty remembering conjunctions of features, no research has yet investigated analogous age related binding deficits in VWM. This is a critical oversight because, given the current state of the science, it is unknown whether these deficits are specific to the long-term memory system, or if they originate in VWM. The project interweaves three strands of research that each investigate whether older adults have more difficulty creating, maintaining, and updating bound multi-feature object representations than younger adults. This theoretical program of enquiry will provide insight into the cognitive architecture of VWM and how this system changes with age, and its outcomes will have wide ranging multi-disciplinary applications in applied theory and intervention techniques that may reduce the adverse consequences of aging on memory.

500 000 €

Start date: 2008-09-01, End date: 2011-08-31

AppSAM will unlock the synthetic capability of S-adenosyl¬methionine (SAM)-dependent methyltransferases and radical SAM enzymes for application in environmentally friendly and fully sustainable reactions. The biotechnological application of these enzymes will provide access to chemo-, regio- and stereoselective methylations and alkylations, as well as to a wide range of complex rearrangement reactions that are currently not possible through traditional approaches. Methylation reactions are of particular interest due to their importance in epigenetics, cancer metabolism and the development of novel pharmaceuticals. As chemical methylation methods often involve toxic compounds and rarely exhibit the desired selectivity and specificity, there is an urgent need for new, environmentally friendly methodologies. The proposed project will meet these demands by the provision of modular in vitro and in vivo systems that can be tailored to specific applications. In the first phase of AppSAM, efficient in vitro SAM-regeneration systems will be developed for use with methyltransferases as well as radical SAM enzymes. To achieve this aim, enzymes from different biosynthetic pathways will be combined in multi-enzyme cascades; methods from enzyme and reaction engineering will be used for optimisation. The second phase of AppSAM will address the application on a preparative scale. This will include the isolation of pure product from the in vitro systems, reactions using immobilised enzymes and extracts from in vivo productions. In addition to E. coli, the methylotrophic bacterium Methylobacter extorquens AM1 will be used as a host for the in vivo systems. M. extorquens can use C1 building blocks such as methanol as the sole carbon source, thereby initiating the biotechnological methylation process from a green source material and making the process fully sustainable, as well as being compatible with an envisaged “methanol economy”.

1 499 219 €

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

AQSuS aims at experimentally implementing analogue quantum simulation of interacting spin models in two-dimensional geometries. The proposed experimental approach paves the way to investigate a broad range of currently inaccessible quantum phenomena, for which existing analytical and numerical methods reach their limitations. Developing precisely controlled interacting quantum systems in 2D is an important current goal well beyond the field of quantum simulation and has applications in e.g. solid state physics, computing and metrology. To access these models, I propose to develop a novel circuit quantum-electrodynamics (cQED) platform based on the 3D transmon qubit architecture. This platform utilizes the highly engineerable properties and long coherence times of these qubits. A central novel idea behind AQSuS is to exploit the spatial dependence of the naturally occurring dipolar interactions between the qubits to engineer the desired spin-spin interactions. This approach avoids the complicated wiring, typical for other cQED experiments and reduces the complexity of the experimental setup. The scheme is therefore directly scalable to larger systems. The experimental goals are: 1) Demonstrate analogue quantum simulation of an interacting spin system in 1D & 2D. 2) Establish methods to precisely initialize the state of the system, control the interactions and readout single qubit states and multi-qubit correlations. 3) Investigate unobserved quantum phenomena on 2D geometries e.g. kagome and triangular lattices. 4) Study open system dynamics with interacting spin systems. AQSuS builds on my backgrounds in both superconducting qubits and quantum simulation with trapped-ions. With theory collaborators my young research group and I have recently published an article in PRB [9] describing and analysing the proposed platform. The ERC starting grant would allow me to open a big new research direction and capitalize on the foundations established over the last two years.

1 498 515 €

Start date: 2017-04-01, End date: 2022-03-31

Globular clusters (GCs) are enigmatic objects that hide a wealth of information. They are the living fossils of the history of their native galaxies and the record keepers of the violent events that made them change their domicile. This proposal aims to mine GCs as living fossils of galaxy evolution to address fundamental questions in astrophysics: (1) Do satellite galaxies merge as predicted by the hierarchical build-up of galaxies? (2) Which are the seeds of supermassive black holes in the centres of galaxies? (3) How did star formation originate in the earliest phases of galaxy formation? To answer these questions, novel population-dependent dynamical modelling techniques are required, whose development the PI has led over the past years. This uniquely positions him to take full advantage of the emerging wealth of chemical and kinematical data on GCs. Following the tidal disruption of satellite galaxies, their dense GCs, and maybe even their nuclei, are left as the most visible remnants in the main galaxy. The hierarchical build-up of their new host galaxy can thus be unearthed by recovering the GCs’ orbits. However, currently it is unclear which of the GCs are accretion survivors. Actually, the existence of a central intermediate mass black hole (IMBH) or of multiple stellar populations in GCs might tell which ones are accreted. At the same time, detection of IMBHs is important as they are predicted seeds for supermassive black holes in galaxies; while the multiple stellar populations in GCs are vital witnesses to the extreme modes of star formation in the early Universe. However, for every putative dynamical IMBH detection so far there is a corresponding non-detection; also the origin of multiple stellar populations in GCs still lacks any uncontrived explanation. The synergy of novel techniques and exquisite data proposed here promises a breakthrough in this emerging field of dynamical archeology with GCs as living fossils of the past of galaxies.

1 999 250 €

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

Carbon Nanotubes (CNTs) are considered to be one of 21st century’s most promising materials and over the past decade, tremendous scientific advances have been achieved in the synthesis and processing of these materials. However, the uptake of CNTs by high-tech industry is hampered by a lack of high-throughput processes to structure CNTs into aligned and densely packed assemblies. This is key to fabricate next generation CNT devices, and to date, the CNT community is still struggling to achieve this, especially over large areas. As part of the ERC Starting Grant HiENA, we are pioneering a potentially disruptive strategy to control the packing of CNTs and to fabricate large area films of aligned CNT. In this process, we start from newly developed ultra-high density dispersion of CNTs which can form liquid crystal domains. These domains are aligned by controlling shear in a custom designed coating head which then continuously dispenses the CNTs on a roll-to-roll coater which was recently purchased by the host group. To quantify the performance of the proposed technology, the parameter space of the coating process will be mapped out in terms of throughput, film thickness, uniformity, and conductivity. Finally, we devised a two-step commercialisation plan which targets less to more demanding markets including thin film heaters, ultra-lightweight electro-magnetic shields, as well as interconnects and sensors for flexible electronics. We believe this project is timely on the one hand because of the technology push of improved CNT processing and on the other hand by the pull from several new markets including flexible electronics and the rise of the Internet of Things which will require a drastic increase in low cost electronic manufacturing technologies. The ERC Proof of Concept grant ARENA aspires to contribute to this need by taking a leap forward in the large scale processing of next generation CNT devices.

149 963 €

Start date: 2017-07-01, End date: 2018-12-31

Knowledge is an anthropological constant that is indissociable from the birth and interactions of human societies, but is at best a secondary concern for scholars of international relations and globalization. Contemporary global studies are thus unable to account for the co-constitution of knowledge and politics at a macro-scale, and remain especially blind to the historical patterns of epistemic development that operate at the level of the species as a whole and have shaped its global political history in specific, path-dependent ways up to now. ARTEFACT is the first project to pursue a knowledge-centered investigation of global politics. It is uniquely grounded in an anthropological approach that treats globalization and human knowledges beyond their modern manifestations, from the longue-durée perspective of our species’ social history. 'The global as artefact' is more than a metaphor. It reflects the premise that human collectives 'make' the political world not merely through ideas, language, or norms, but primordially through the material infrastructures, solutions, objects, practices, and skills they develop in response to evolving structural challenges. ARTEFACT takes agriculture as an exemplary and especially timely case-study to illuminate the entangled global histories of knowledge and politics, analyzing and comparing four increasingly inclusive 'global political systems' of the Ancient, Medieval, Modern, and Contemporary eras and their associated agrarian socio-epistemic revolutions. ARTEFACT ultimately aims to 1) develop an original theory of the global, 2) launch Global Knowledge Studies as a new cross-disciplinary domain of systematic empirical and theoretical study, and 3) push the respective boundaries of the anthropology of knowledge, global history, and international theory beyond the state-of-the-art and toward a holistic understanding that can illuminate how past trends of socio-epistemic evolution might shape future paths of global life.

1 428 165 €

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

The ERC starting grant GECOMETHODS, on which this POC is based, tackled problems of diffusion equations via geometric control methods. One of the most striking achievements of the project has been the development of an algorithm of image reconstruction based mainly on non-isotropic diffusion. This algorithm is bio-mimetic in the sense that it replicates the way in which the primary visual cortex V1 of mammals processes the signals arriving from the eyes. It has performances that are at the state of the art in image processing. These results together with others obtained in the ERC project show that image processing algorithms based on the functional architecture of V1 can go very far. However, the exceptional performances of the primary visual cortex V1 rely not only on the particular algorithm used, but also on the fact that such algorithm “runs” on a dedicated hardware having the following features: 1. an exceptional level of parallelism; 2. connections that are well adapted to transmit information in a non-isotropic way as it is required by the algorithms of image reconstruction and recognition. The idea of this POC is to create a dedicated hardware (called ARTIV1) emulating the functional architecture of V1 and hence having on one hand a huge degree of parallelism and on the other hand connections among the CPUs that reflect the non-isotropic structure of the visual cortex V1. Such a hardware that we plan to build as an integrated circuit with an industrial partner will be a veritable artificial visual cortex. It will be fully programmable and it will be able to perform many biomimetic image processing tasks that we expect to be exceptionally performant. ARTIV1 will come to the marked accompanied by some dedicated software for image reconstruction and image recognition. However we expect that other applications will be developed by customers, as for instance softwares for optical flow estimation or for sound processing.

149 937 €

Start date: 2017-04-01, End date: 2018-09-30

Atmospheric Gas-to-Particle conversion (ATM-GTP) is a 5-year project focusing on one of the most critical atmospheric processes relevant to global climate and air quality: the first steps of atmospheric aerosol particle formation and growth. The project will concentrate on the currently lacking environmentally-specific knowledge about the interacting, non-linear, physical and chemical atmospheric processes associated with nano-scale gas-to-particle conversion (GTP). The main scientific objective of ATM-GTP is to create a deep understanding on atmospheric GTP taking place at the sub-5 nm size range, particularly in heavily-polluted Chinese mega cities like Beijing and in pristine environments like Siberia and Nordic high-latitude regions. We also aim to find out how nano-GTM is associated with air quality-climate interactions and feedbacks. We are interested in quantifying the effect of nano-GTP on the COBACC (Continental Biosphere-Aerosol-Cloud-Climate) feedback loop that is important in Arctic and boreal regions. Our approach enables to point out the effective reduction mechanisms of the secondary air pollution by a factor of 5-10 and to make reliable estimates of the global and regional aerosol loads, including anthropogenic and biogenic contributions to these loads. We can estimate the future role of Northern Hemispheric biosphere in reducing the global radiative forcing via the quantified feedbacks. The project is carried out by the world-leading scientist in atmospheric aerosol science, being also one of the founders of terrestrial ecosystem meteorology, together with his research team. The project uses novel infrastructures including SMEAR (Stations Measuring Ecosystem Atmospheric Relations) stations, related modelling platforms and regional data from Russia and China. The work will be carried out in synergy with several national, Nordic and EU research-innovation projects: Finnish Center of Excellence-ATM, Nordic CoE-CRAICC and EU-FP7-BACCHUS.

2 500 000 €

Start date: 2017-06-01, End date: 2022-05-31

The ongoing miniaturization in nanotechnology and functional materials puts an ever increasing focus on the development of three-dimensional (3D) nanostructures, such as quantum dot arrays, structured nanowires, or non-trivial topological magnetic textures such as skyrmions, which permit a better performance of logical or memory devices in terms of speed and energy efficiency. To develop and advance such technologies and to improve the understanding of the underlying fundamental solid state physics effects, the nondestructive and quantitative 3D characterization of physical, e.g., electric or magnetic, fields down to atomic resolution is indispensable. Current nanoscale metrology methods only inadequately convey this information, e.g., because they probe surfaces, record projections, or lack resolution. AToM will provide a ground-breaking tomographic methodology for current nanotechnology by mapping electric and magnetic fields as well as crucial properties of the underlying atomic structure in solids, such as the chemical composition, mechanical strain or spin configuration in 3D down to atomic resolution. To achieve that goal, advanced holographic and tomographic setups in the Transmission Electron Microscope (TEM) are combined with novel computational methods, e.g., taking into account the ramifications of electron diffraction. Moreover, fundamental application limits are overcome (A) by extending the holographic principle, requiring coherent electron beams, to quantum state reconstructions applicable to electrons of any (in)coherence; and (B) by adapting a unique in-situ TEM with a very large sample chamber to facilitate holographic field sensing down to very low temperatures (6 K) under application of external, e.g., electric, stimuli. The joint development of AToM in response to current problems of nanotechnology, including the previously mentioned ones, is anticipated to immediately and sustainably advance nanotechnology in its various aspects.

1 499 602 €

Start date: 2017-01-01, End date: 2021-12-31

Quantum information science and atom optics are among the most active fields in modern physics. In recent years, many theoretical efforts have been made to combine these two fields. Recent experimental progresses have shown the in-principle possibility to perform scalable quantum information processing (QIP) with linear optics and atomic ensembles. The main purpose of the present project is to use atomic qubits as quantum memory and exploit photonic qubits for information transfer and processing to achieve efficient linear optics QIP. On the one hand, utilizing the interaction between laser pulses and atomic ensembles we will experimentally investigate the potentials of atomic ensembles in the gas phase to build quantum repeaters for long-distance quantum communication, that is, to develop a new technological solution for quantum repeaters making use of the effective qubit-type entanglement of two cold atomic ensembles by a projective measurement of individual photons by spontaneous Raman processes. On this basis, we will further investigate the advantages of cold atoms in an optical trap to enhance the coherence time of atomic qubits beyond the threshold for scalable realization of quantum repeaters. Moreover, building on our long experience in research on multi-photon entanglement, we also plan to perform a number of significant experiments in the field of QIP with particular emphasis on fault-tolerant quantum computation, photon-loss-tolerant quantum computation and cluster-state based quantum simulation. Finally, by combining the techniques developed in the above quantum memory and multi-photon interference experiments, we will further experimentally investigate the possibility to achieve quantum teleportation between photonic and atomic qubits, quantum teleportation between remote atomic qubits and efficient entanglement generation via classical feed-forward. The techniques that will be developed in the present project will lay the basis for future large scale

1 435 000 €

Start date: 2008-07-01, End date: 2013-12-31

In many prevalent autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) autoantibodies are used as diagnostic and prognostic tools. Several of these autoantibodies target proteins that have been post-translationally modified (PTM). Examples of such modifications are citrullination and carbamylation. The success of B cell-targeted therapies in many auto-antibody positive diseases suggests that B cell mediated auto-immunity is playing a direct pathogenic role. Despite the wealth of information on the clinical associations of these anti-PTM protein antibodies as biomarkers we have currently no insight into why these antibodies are formed. Immunization studies reveal that PTM proteins can induce antibody responses even in the absence of exogenous adjuvant. The reason why these PTM proteins have ‘autoadjuvant’ properties that lead to a breach of tolerance is currently unknown. In this proposal, I hypothesise that the breach of tolerance towards PTM proteins is mediated by complement factors that bind directly to these PTM. Our preliminary data indeed reveal that several complement factors bind specifically to PTM proteins. Complement could be involved in the autoadjuvant property of PTM proteins as next to killing pathogens complement can also boost adaptive immune responses. I plan to unravel the importance of the complement–PTM protein interaction by answering these questions: 1) What is the physiological function of complement binding to PTM proteins? 2) Is the breach of tolerance towards PTM proteins influenced by complement? 3) Can the adjuvant function of PTM be used to increase vaccine efficacy and/or decrease autoreactivity? With AUTOCOMPLEMENT I will elucidate how PTM-reactive B cells receive ‘autoadjuvant’ signals. This insight will impact on patient care as we can now design strategies to either block unwanted ‘autoadjuvant’ signals to inhibit autoimmunity or to utilize ‘autoadjuvant’ signals to potentiate vaccination.

1 999 803 €

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

This project focuses on the historical analysis of institutions and their impact on economic development through the investigation of a legal instrument – general average (GA) – which underpins maritime trade by redistributing damages’ costs across all interested parties. This will be pursued through the comparative investigation of GA in those European countries where substantial data exists: Italy, Spain, England, France and the Low Countries (1500-1800). Average and insurance were both created in the Middle Ages to facilitate trade through the redistribution of risk. Insurance has been widely studied, average – the expenses which can befall ships and cargoes from the time of their loading aboard until their unloading (due to accidents, jettison, and unexpected costs) – has been neglected. GA still plays an essential role in the redistribution of transaction costs, and being a form of strictly mutual self-protection, never evolved into a speculative financial instrument as insurance did; it therefore represents an excellent case of long-term effectiveness of a non-market economic phenomenon. Although the principle behind GA was very similar across Europe, in practice there were substantial differences in declaring and adjudicating claims. GA reports provide unparalleled evidence on maritime trade which, analysed quantitatively and quantitatively through a novel interdisciplinary approach, will contribute to the reassessment of the role played by the maritime sector in fostering economic growth during the early modern first globalization, when GA was the object of fierce debates on state jurisdiction and standardization of practice. Today they are regulated by the York-Antwerp Rules (YAR), currently under revision. This timely conjuncture provides plenty of opportunities for active engagement with practitioners, thereby fostering a creative dialogue on GA historical study and its future development to better face the challenges of mature globalization.

1 854 256 €

Start date: 2017-07-01, End date: 2022-06-30

Axions are hypothetical particles whose existence would solve two major problems: the strong P, T problem (a major blemish on the standard model); and the dark matter problem. It is a most important goal to either observe or rule out the existence of a cosmic axion background. It appears that decisive observations may be possible, but only after orchestrating insight from specialities ranging from quantum field theory and astrophysical modeling to ultra-low noise quantum measurement theory. Detailed predictions for the magnitude and structure of the cosmic axion background depend on cosmological and astrophysical modeling, which can be constrained by theoretical insight and numerical simulation. In parallel, we must optimize strategies for extracting accessible signals from that very weakly interacting source. While the existence of axions as fundamental particles remains hypothetical, the equations governing how axions interact with electromagnetic fields also govern (with different parameters) how certain materials interact with electromagnetic fields. Thus those materials embody “emergent” axions. The equations have remarkable properties, which one can test in these materials, and possibly put to practical use. Closely related to axions, mathematically, are anyons. Anyons are particle-like excitations that elude the familiar classification into bosons and fermions. Theoretical and numerical studies indicate that they are common emergent features of highly entangled states of matter in two dimensions. Recent work suggests the existence of states of matter, both natural and engineered, in which anyon dynamics is both important and experimentally accessible. Since the equations for anyons and axions are remarkably similar, and both have common, deep roots in symmetry and topology, it will be fruitful to consider them together.

2 324 391 €

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

Early life immune balance is essential for survival and establishment of healthy immunity in later life. We aim to define how age-dependent regulation of dendritic cell (DC) development contributes to this crucial immune balance. DCs are versatile controllers of immunity that in neonates are qualitatively distinct from adults. Why such age-dependent differences exist is unclear but newborn DCs are considered underdeveloped and functionally immature. Using ontogenetic tracing of conventional DC precursors, I have found a previously unappreciated developmental heterogeneity of DCs that is particularly prominent in young mice. Preliminary data indicate that distinct waves of DC poiesis contribute to the functional differences between neonatal and adult DCs. I hypothesize that the neonatal DC compartment is not immature but rather that DC poiesis is developmentally regulated to create essential age-dependent immune balance. Further, I have identified a unique situation in early life to address a fundamental biological question, namely to what extent cellular function is pre-programmed by developmental origin (nature) versus environmental factors (nurture). In this proposal, we will first use novel models to fate map the origin of the DC compartment with age. We will then define to what extent cellular origin determines age-dependent functions of DCs in immunity. Using innovative comparative gene expression profiling and integrative epigenomic analysis the cell intrinsic mechanisms regulating the age-dependent functions of DCs will be characterized. Because environmental factors in utero and after birth critically influence immune balance, we will finally define the impact of maternal infection and metabolic disease, as well as early microbial encounter on DC poiesis. Characterizing how developmentally regulated DC poiesis shapes the unique features of early life immunity will provide novel insights into immune development that are vital to advance vaccine strategies.

1 500 000 €

Start date: 2017-06-01, End date: 2022-05-31

A new generation of galaxy surveys will soon start measuring the spatial distribution of millions of galaxies over a broad range of redshifts, offering an imminent opportunity to discover new physics. A detailed comparison of these measurements with theoretical models of galaxy clustering may reveal a new fundamental particle, a breakdown of General Relativity, or a hint on the nature of cosmic acceleration. Despite a large progress in the analytic treatment of structure formation in recent years, traditional clustering models still suffer from large uncertainties. This limits cosmological analyses to a very restricted range of scales and statistics, which will be one of the main obstacles to reach a comprehensive exploitation of future surveys. Here I propose to develop a novel simulation--based approach to predict galaxy clustering. Combining recent advances in computational cosmology, from cosmological N--body calculations to physically-motivated galaxy formation models, I will develop a unified framework to directly predict the position and velocity of individual dark matter structures and galaxies as function of cosmological and astrophysical parameters. In this formulation, galaxy clustering will be a prediction of a set of physical assumptions in a given cosmological setting. The new theoretical framework will be flexible, accurate and fast: it will provide predictions for any clustering statistic, down to scales 100 times smaller than in state-of-the-art perturbation--theory--based models, and in less than 1 minute of CPU time. These advances will enable major improvements in future cosmological constraints, which will significantly increase the overall power of future surveys maximising our potential to discover new physics.

1 484 240 €

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

In the last forty years, researchers in the Field of Migration and Ethnic Studies looked at the integration of migrants and their descendants. Concepts, methodological tools and theoretical frameworks have been developed to measure and predict integration outcomes both across different ethnic groups and in comparison with people of native descent. But are we also looking into the actual integration of the receiving group of native ‘white’ descent in city contexts where they have become a numerical minority themselves? In cities like Amsterdam, now only one in three youngsters under age fifteen is of native descent. This situation, referred to as a majority-minority context, is a new phenomenon in Western Europe and it presents itself as one of the most important societal and psychological transformations of our time. I argue that the field of migration and ethnic studies is stagnating because of the one-sided focus on migrants and their children. This is even more urgent given the increased ant-immigrant vote. These pressing scientific and societal reasons pushed me to develop the project BAM (Becoming A Minority). The project will be executed in three harbor cities, Rotterdam, Antwerp and Malmö, and three service sector cities, Amsterdam, Frankfurt and Vienna. BAM consists of 5 subprojects: (1) A meta-analysis of secondary data on people of native ‘white’ descent in the six research sites; (2) A newly developed survey for the target group; (3) An analysis of critical circumstances of encounter that trigger either positive or rather negative responses to increased ethnic diversity (4) Experimental diversity labs to test under which circumstances people will change their attitudes or their actions towards increased ethnic diversity; (5) The formulation of a new theory of integration that includes the changed position of the group of native ‘white’ descent as an important actor.

2 499 714 €

Start date: 2017-11-01, End date: 2022-10-31

The aim of BAPS is to develop a ground-breaking simulation model of international migration, based on a population of intelligent, cognitive agents, their social networks and institutions, all interacting with one another. The project will transform the study of migration – one of the most uncertain population processes and a top-priority EU policy area – by offering a step change in the way it can be understood, predicted and managed. In this way, BAPS will effectively integrate behavioural and social theory with modelling. To develop micro-foundations for migration studies, model design will follow cutting-edge developments in demography, statistics, cognitive psychology and computer science. BAPS will also offer a pioneering environment for applying the findings in practice through a bespoke modelling language. Bayesian statistical principles will be used to design innovative computer experiments, and learn about modelling the simulated individuals and the way they make decisions. In BAPS, we will collate available information for migration models; build and test the simulations by applying experimental design principles to enhance our knowledge of migration processes; collect information on the underpinning decision-making mechanisms through psychological experiments; and design software for implementing Bayesian agent-based models in practice. The project will use various information sources to build models bottom-up, filling an important epistemological gap in demography. BAPS will be carried out by the Allianz European Demographer 2015, recognised as a leader in the field for methodological innovation, directing an interdisciplinary team with expertise in demography, agent-based models, statistical analysis of uncertainty, meta-cognition, and computer simulations. The project will open up exciting research possibilities beyond demography, and will generate both academic and practical impact, offering methodological advice for policy-relevant simulations.

1 455 590 €

Start date: 2017-06-01, End date: 2021-05-31

This interdisciplinary project will show that inter-imperial zones and small to mid-size regional networks of exchange were crucial for ancient Transeurasian exchange connections. It will demonstrate the significance of exchange in imperial frontier zones emerging from political, economic, infrastructural, institutional and technological development within empires. This will lead to a new conceptual frame for analyzing inter-imperiality and the morphology of exchange networks within and across imperial zones. The centuries from 300 BCE to 300 CE were a period of accelerated empire transformation involving also new regions of the Afro-Eurasian world. Consumption centres shifted, affecting production, settlement, and regional exchange networks. They changed the dynamics of exchange, created new geographies, and greater cultural convergence between imperial spheres of influence. The development of imperial frontier zones of intense exchange and mobility (e.g. Northern China, Bactria, Gandhara, Syria, and the Red Sea/Gulf/Indian Ocean coasts) was related to imperial hinterlands, their fiscal-military-administrative regimes, the development of media of exchange and infrastructures, settlement, urban growth, and so on. It was also related to new forms and levels of consumption in imperial centres. In order to understand Transeurasian connectivity, the interdependence of frontier zone and inner-imperial development is crucial. We will reveal that competitions for social power within empires mobilized and concentrated resources reclaimed from natural landscapes and subsistence economies. Greater mobility of resources, both human and material, endowed competitions for power with economic force, feeding into inter-imperial prestige economies and trade. This new model of Afro-Eurasian connectivity will abandon some problematic assumptions of Silk Road trade, while maintaining the Afro-Eurasian macro-region as a meaningful unit for cultural and economic analysis.

2 498 750 €

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

My research encompasses the application of novel methods and strategies in the field of low energy particle physics. The goal of the presented program is to lead an independent and highly competitive experiment to search for a CP violating neutron electric dipole moment (nEDM), as well as for new exotic interactions using highly sensitive neutron and proton spin resonance techniques. The measurement of the nEDM is considered to be one of the most important fundamental physics experiments at low energy. It represents a promising route for finding new physics beyond the standard model (SM) and describes an important search for new sources of CP violation in order to understand the observed large baryon asymmetry in our universe. The main project will follow a novel concept based on my original idea, which plans to employ a pulsed neutron beam at high intensity instead of the established use of storable ultracold neutrons. This complementary and potentially ground-breaking method provides the possibility to distinguish between the signal due to a nEDM and previously limiting systematic effects, and should lead to an improved result compared to the present best nEDM beam experiment. The findings of these investigations will be of paramount importance and will form the cornerstone for the success of the full-scale experiment intended for the European Spallation Source. A second scientific question will be addressed by performing spin precession experiments searching for exotic short-range interactions and associated light bosons. This is a vivid field of research motivated by various extensions to the SM. The goal of these measurements, using neutrons and protons, is to search for additional interactions such new bosons mediate between ordinary particles. Both topics describe ambitious and unique efforts. They use related techniques, address important questions in fundamental physics, and have the potential of substantial scientific implications and high-impact results.

1 404 062 €

Start date: 2017-04-01, End date: 2022-03-31