ERC FUNDED PROJECTS

Many anti-angiogenic drugs are clinically used in several types of cancer to block angiogenesis, impair tumor growth, progression and dissemination. Nevertheless, clinical trials report emergence of resistance to treatment and a failure in long-lasting effects of these therapies. To date, resistant patients do not currently have any established, proven alternative therapeutic possibility and the medical field is moving towards a careful selection of subgroups or subtypes of patients that have to be treated with each one of the available second-line targeted drugs. For this relevant unmet medical need, many laboratories and pharmaceutical companies have focused on developing new biomarkers and new drugs to fight anti-angiogenic resistance, but up to date, there is no proven established biomarker or method to predict which patient’s tumor is resistant to antiangiogenic therapies and which drug is capable of blocking this resistance to therapy. AngioResist PoC aims at solving the existing patient selection gap in the treatment of cancer that is therapeutically resistant to antiangiogenic drugs. Based on data generated from our ERC project and two filed European Patent applications, AngioResist PoC will transform the acquired basic knowledge into an Innovation project, to validate a novel biomarker of response/resistance to antiangiogenics together with a new inhibitor for the treatment of these selected patients. The project will coordinately perform the preclinical phases of development of the drug compound and the biomarker, with the final aim of licensing them both to a selected partner during the clinical phases. Together with our licensee, we aim at the final distribution of a therapeutic drug that will be delivered with a biomarker kit for the selection and treatment of cancer patients resistant to antiangiogenic drugs.

149 932 €

Start date: 2016-09-01, End date: 2018-02-28

In many European countries with ostensibly liberal abortion laws, women face legal restrictions to abortion beyond the first trimester of pregnancy, as well as other barriers to legal abortion, in particular shortages of providers willing and able to offer abortion due to poor training and to conscientious objection among physicians. The Council of Europe has recognized that conscientious objection can make access to safe abortion more difficult or impossible, particularly in rural areas and for low income women, who are forced to travel far to seek abortion care, including abroad. The WHO also highlights that delaying abortion care increases risks for women’s reproductive health. Despite the relevance of this topic from a public health and human rights perspective, the impact of procedural and social barriers to legal abortion on women in countries with ostensibly liberal abortion laws has not been studied by social scientists in Europe. This five-year research project is envisaged as a ground-breaking multi-disciplinary, mixed-methods investigation that will fill this gap, by capitalizing on previous, pioneer anthropological research of the PI on abortion and conscientious objection. It will contribute to the anthropology of reproduction in Europe, and particularly to the existing literature on abortion, conscientious objection and the medicalization of reproduction, and to the international debate on gender inequalities and citizenship, by exploring how barriers to legal abortion are constructed and how women embody and challenge them in different countries, by travelling or seeking illegal abortion, as well as their conceptualizations of abortion and their self perception as moral/political subjects. The project will be carried out in France, Italy and Spain, where the few existing studies show that women face several barriers to legal abortion as well as in the UK, the Netherlands and Spain, where Italian and French women travel to seek abortion care.

1 495 753 €

Start date: 2016-10-01, End date: 2021-09-30

The two fundamental challenges of this project are the integration of medieval Jewries and their histories within the framework of European history without undermining their distinct communal status and the creation of a history of everyday medieval Jewish life that includes those who were not part of the learned elite. The study will focus on the Jewish communities of northern Europe (roughly modern Germany, northern France and England) from 1100-1350. From the mid-thirteenth century these medieval Jewish communities were subject to growing persecution. The approaches proposed to access daily praxis seek to highlight tangible dimensions of religious life rather than the more common study of ideologies to date. This task is complex because the extant sources in Hebrew as well as those in Latin and vernacular were written by the learned elite and will require a broad survey of multiple textual and material sources. Four main strands will be examined and combined: 1. An outline of the strata of Jewish society, better defining the elites and other groups. 2. A study of select communal and familial spaces such as the house, the synagogue, the market place have yet to be examined as social spaces. 3. Ritual and urban rhythms especially the annual cycle, connecting between Jewish and Christian environments. 4. Material culture, as objects were used by Jews and Christians alike. Aspects of material culture, the physical environment and urban rhythms are often described as “neutral” yet will be mined to demonstrate how they exemplified difference while being simultaneously ubiquitous in local cultures. The deterioration of relations between Jews and Christians will provide a gauge for examining change during this period. The final stage of the project will include comparative case studies of other Jewish communities. I expect my findings will inform scholars of medieval culture at large and promote comparative methodologies for studying other minority ethnic groups

1 941 688 €

Start date: 2016-11-01, End date: 2021-10-31

The global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the global fishery has provided large economic benefits, but in so doing has restructured ecosystems by removing most of the large animal biomass, a major top-down change. Although there has been a tremendous amount of research into isolated aspects of these impacts, the development of a holistic understanding of the full interactions between physics, chemistry, ecology and economic activity might appear impossible, given the myriad complexities. This proposal lays out a strategy to assemble a team of trans-disciplinary expertise, that will develop a unified, data-constrained, grid-based modeling framework to represent the most important interactions of the global human-ocean system. Building this framework requires solving a series of fundamental problems that currently hinder the development of the full model. If these problems can be solved, the resulting model will reveal novel emergent properties and open the doors to a range of previously unexplored questions of high impact across a range of disciplines. Key questions include the ways in which animals interact with oxygen minimum zones with implications for fisheries, the impacts fish harvesting may have on nutrient recycling, spatio-temporal interactions between managed and unmanaged fisheries, and fundamental questions about the relationships between fish price, fishing cost, and multiple markets in a changing world. Just as the first coupled ocean-atmosphere models revealed a wealth of new behaviours, the coupled human-ocean model proposed here has the potential to launch multiple new fields of enquiry. It is hoped that the novel approach will contribute to a paradigm shift that treats human activity as one component within the framework of the Earth System.

1 600 000 €

Start date: 2016-07-01, End date: 2021-06-30

In order to celebrate mathematics in the new millennium, the Clay Mathematics Institute established seven $1.000.000 Prize Problems. One of these is the conjecture of Birch and Swinnerton-Dyer (BSD), widely open since the 1960's. The main object of this proposal is developing innovative and unconventional strategies for proving groundbreaking results towards the resolution of this problem and their generalizations by Bloch and Kato (BK). Breakthroughs on BSD were achieved by Coates-Wiles, Gross, Zagier and Kolyvagin, and Kato. Since then, there have been nearly no new ideas on how to tackle BSD. Only very recently, three independent revolutionary approaches have seen the light: the works of (1) the Fields medalist Bhargava, (2) Skinner and Urban, and (3) myself and my collaborators. In spite of that, our knowledge of BSD is rather poor. In my proposal I suggest innovating strategies for approaching new horizons in BSD and BK that I aim to develop with the team of PhD and postdoctoral researchers that the CoG may allow me to consolidate. The results I plan to prove represent a departure from the achievements obtained with my coauthors during the past years: I. BSD over totally real number fields. I plan to prove new ground-breaking instances of BSD in rank 0 for elliptic curves over totally real number fields, generalizing the theorem of Kato (by providing a new proof) and covering many new scenarios that have never been considered before. II. BSD in rank r=2. Most of the literature on BSD applies when r=0 or 1. I expect to prove p-adic versions of the theorems of Gross-Zagier and Kolyvagin in rank 2. III. Darmon's 2000 conjecture on Stark-Heegner points. I plan to prove Darmon’s striking conjecture announced at the ICM2000 by recasting it in terms of special values of p-adic L-functions.

1 428 588 €

Start date: 2016-09-01, End date: 2021-08-31

Clinical experience with globally-acting cannabinoid-1 receptor (CB1R) antagonists revealed the benefits of blocking CB1Rs for the treatment of obesity and diabetes. However, their use is hampered by increased CNS-mediated side effects. Recently, I have demonstrated that peripherally-restricted CB1R antagonists have the potential to treat the metabolic syndrome without eliciting these adverse effects. While these results are promising and are currently being developed into the clinic, our ability to rationally design CB1R blockers that would target a diseased organ is limited. The current proposal aims to develop and test cell- and organelle-specific CB1R antagonists. To establish this paradigm, I will focus our interest on the kidney, since chronic kidney disease (CKD) is the leading cause of increased morbidity and mortality of patients with diabetes. Our first goal will be to characterize the obligatory role of the renal proximal tubular CB1R in the pathogenesis of diabetic renal complications. Next, we will attempt to link renal proximal CB1R with diabetic mitochondrial dysfunction. Finally, we will develop proximal tubular (cell-specific) and mitochondrial (organelle-specific) CB1R blockers and test their effectiveness in treating CKD. To that end, we will encapsulate CB1R blockers into biocompatible polymeric nanoparticles that will serve as targeted drug delivery systems, via their conjugation to targeting ligands. The implications of this work are far reaching as they will (i) point to renal proximal tubule CB1R as a novel target for CKD; (ii) identify mitochondrial CB1R as a new player in the regulation of proximal tubular cell function, and (iii) eventually become the drug-of-choice in treating diabetic CKD and its comorbidities. Moreover, this work will lead to the development of a novel organ-specific drug delivery system for CB1R blockers, which could be then exploited in other tissues affected by obesity, diabetes and the metabolic syndrome.

1 500 000 €

Start date: 2016-04-01, End date: 2021-03-31

An innovative methodology has been developed in the field of copper-catalyzed cross coupling catalysis, with the goal of developing more efficient and sustainable synthetic protocols used by Chemical and Pharmaceutical Industries. Successful research developed within the ERC-2011-StG-277801 project has led to discover new methodologies for sustainable catalytic transformations using copper catalysts to form C-C or C-heteroatom bonds, finding out the feasibility of uncommon copper(III) species as key intermediates. This new methodology features three main advantages: a) Precise design of the auxiliary ligands used in these transformations is a pathway of a more sustainable reactivity; b) competitive alternative to the price and toxicity disadvantages of Pd-based catalysts; and c) it can impart distinct selectivity that will broaden the scope of synthetic tools. The goal of the present CatalApp project is to study the feasibility of bringing this technology into a pre-commercial stage, with the aim of accelerating the access to the market of this new methodology. The pre-commercial stage will be orientated into: 1) A technical perspective that will be achieved by scaling-up current gram-scale methodologies to kilogram scale procedures. 2) An Economic and legal perspective, which include an analysis of Intellectual Property (IP) protection needs, evaluation of patent filling procedures required to provide an adequate protection of the different developed methodologies, a market study to identify specific potential uses of these synthetic tools, and a review of potential commercialisation partners. The expected outcomes of the PoC project will be the commercial availability of a portfolio of synthetic methodologies based on Copper, designed for specific applications. The strive of the CatalApp PoC project is making available these new methodologies in response to the demand of the industry and investors in order to ensure its results will be exploited successfully.

147 500 €

Start date: 2016-08-01, End date: 2018-01-31

We propose to carry out a project which will produce a decisive step towards improving the accuracy of the Hubble constant as determined from the Cepheid-SN Ia method to 1%, by using 28 extremely rare eclipsing binary systems in the LMC which offer the potential to determine their distances to 1%. To achieve this accuracy we will reduce the main error in the binary method by interferometric angular diameter measurements of a sample of red clump stars which resemble the stars in our binary systems. We will check on our calibration with similar binary systems close enough to determine their orbits from interferometry. We already showed the feasibility of our method which yielded the best-ever distance determination to the LMC of 2.2% from 8 such binary systems. With 28 systems and the improved angular diameter calibration we will push the LMC distance uncertainty down to 1% which will allow to set the zero point of the Cepheid PL relation with the same accuracy using the large available LMC Cepheid sample. We will determine the metallicity effect on Cepheid luminosities by a) determining a 2% distance to the more metal-poor SMC with our binary method, and by b) measuring the distances to LMC and SMC with an improved Baade-Wesselink (BW) method. We will achieve this improvement by analyzing 9 unique Cepheids in eclipsing binaries in the LMC our group has discovered which allow factor- of-ten improvements in the determination of all basic physical parameters of Cepheids. These studies will also increase our confidence in the Cepheid-based H0 determination. Our project bears strong synergy to the Gaia mission by providing the best checks on possible systematic uncertainties on Gaia parallaxes with 200 binary systems whose distances we will measure to 1-2%. We will provide two unique tools for 1-3 % distance determinations to individual objects in a volume of 1 Mpc, being competitive to Gaia already at a distance of 1 kpc from the Sun.

2 360 500 €

Start date: 2016-11-01, End date: 2021-10-31

The ERC-funded project BIDECASEOX ERC-239910 has produced a series of chiral catalysts with broad applicability in various commercial fields associated with synthetic organic chemistry. These catalysts are based in earth abundant metals and activate hydrogen peroxide to perform asymmetric introduction of oxygen atoms into readily available and cheap non chiral organic molecules, producing highly valuable chiral products, leaving water as the only byproduct. By virtue of these reactions, valuable chiral products that nowadays are only accessible by expensive enzymatic methods, or in some cases by toxic, expensive and large waste-producing traditional stoichiometric oxidants, become available in a sustainable manner. Pharmaceutical and agricultural industry, polymer chemistry and fine chemistry are envisioned as potential targets for the interest of the catalysts. With the aim of accelerating their access to the market, the present Proof of Concept (PoC) project, named CHIROXCAT, will target to study the feasibility of bringing these catalysts into a pre-commercial stage. This will be achieved by scaling-up current mg-scale synthetic methods, in order to establish economically optimized multigram scale procedures, and by validating their use in the production of representative chiral molecules of potential interest to the fine chemical industry. This PoC activity will also include an analysis of intellectual property (IP) protection needs within the field of application, as well as setting up the basis for any patent filling procedure required to provide an adequate protection of the catalysts and their uses. Moreover, a market study will be conducted to identify specific potential uses of these compounds, and a review of potential commercialisation partners will be carried out. The expected outcomes of the PoC project will be the commercial availability of a portfolio of chiral catalysts based in earth abundant metals with application in chemical

149 750 €

Start date: 2016-05-01, End date: 2017-10-31

This five years research proposal is focused on the development of novel information theoretic concepts and techniques and their usage, as to identify the ultimate communications limits and potential of different cloud radio network structures, in which the central signal processing is migrated to the cloud (remote central units), via fronthaul/backhaul infrastructure links. Moreover, it is also directed to introduce and study the optimal or close to optimal strategies for those systems that are to be motivated by the developed theory. We plan to address wireless networks, having future cellular technology in mind, but the basic tools and approaches to be built and researched are relevant to other communication networks as well. Cloud communication networks motivate novel information theoretic views, and perspectives that put backhaul/fronthaul connections in the center, thus deviating considerably from standard theoretical studies of communications links and networks, which are applied to this domain. Our approach accounts for the fact that in such networks information theoretic separation concepts are no longer optimal, hence isolating simple basic components of the network is essentially suboptimal. The proposed view incorporates, in a unified way, under the general cover of information theory: Multi-terminal distributed networks; Basic and timely concepts of distributed coding and communications; Network communications and primarily network coding, Index coding, as associated with interference alignment and caching; Information-Estimation relations and signal processing, addressing the impact of distributed channel state information directly; A variety of fundamental concepts in optimization and random matrix theories. This path provides a natural theoretical framework directed towards better understanding the potential and limitation of cloud networks on one hand and paves the way to innovative communications design principles on the other.

1 981 782 €

Start date: 2016-07-01, End date: 2021-06-30

Melanoma tumours develop in the pigment cells located in the skin. It is the most aggressive and treatment-resistant type of skin cancer as well as the leading cause of death among skin diseases. Moreover, melanoma’s alarming increase in incidence, especially in the young population, in combination with its propensity for lethal metastasis, illustrates an urgent need for new treatment strategies. In this PoC project, we propose developing an innovative tool, called COMbAT, for designing highly personalized therapies for melanoma patients. Each therapy will be based on existing, already designed drugs and will specifically target the driver mutations present in a patient’s melanoma genome. COMbAT involves the use of novel unique preclinical models designed to express patient-derived mutated genes in melanoma cells in a physiological manner. These models will undergo systematic combinatorial drug screens aiming to target the exact driver mutations present in patients. Such personalized targeting of the patient’s melanoma genetic landscape is key to a significantly improved mortality. Specifically, COMbAT can serve as a unique preclinical tool in the delivery of healthcare, from redefining clinical trials to targeted treatments of melanoma patients to start and a wide range of other cancer types later. Importantly, as COMbAT will allow the increased use of specific targeting of molecular drug targets, it will help to significantly lower the patient’s economic and psychological burden caused by unnecessary chemotherapy. COMbAT also holds the promise of realizing value from enormous past investments in drug candidates that were eliminated due to person-specific toxicities or lack of efficacy. We thus believe that COMbAT will enable the creation of new business models for the pharmaceutical industry which is suffering from patent expirations, threats from biotech companies, regulatory pressures, costly drug development timelines, and backlash from adverse drug reactions.

150 000 €

Start date: 2015-10-01, End date: 2017-03-31

Measurement based quantum computing is one of the most fault-tolerant architectures proposed for quantum information processing. It opens the possibility of performing quantum computing tasks using linear optical systems. An efficient route for measurement based quantum computing utilizes highly entangled states of photons, called cluster states. Propagation and processing quantum information is made possible this way using only single qubit measurements. It is highly resilient to qubit losses. In addition, single qubit measurements of polarization qubits is easily performed with high fidelity using standard optical tools. These features make photonic clusters excellent platforms for quantum information processing. Constructing photonic cluster states, however, is a formidable challenge, attracting vast amounts of research efforts. While in principle it is possible to build up cluster states using interferometry, such a method is of a probabilistic nature and entails a large overhead of resources. The use of entangled photon pairs reduces this overhead by a small factor only. We outline a novel route for constructing a deterministic source of photonic cluster states using a device based on semiconductor quantum dot. Our proposal follows a suggestion by Lindner and Rudolph. We use repeated optical excitations of a long lived coherent spin confined in a single semiconductor quantum dot and demonstrate for the first time practical realization of their proposal. Our preliminary demonstration presents a breakthrough in quantum technology since deterministic source of photonic cluster, reduces the resources needed quantum information processing. It may have revolutionary prospects for technological applications as well as to our fundamental understanding of quantum systems. We propose to capitalize on this recent breakthrough and concentrate on R&D which will further advance this forefront field of science and technology by utilizing the horizons that it opens.

2 502 974 €

Start date: 2016-06-01, End date: 2021-05-31

This project aims at making a breakthrough contribution in the broad area of Control of Partial Differential Equations (PDE) and their numerical approximation methods by addressing key unsolved issues appearing systematically in real-life applications. To this end, we pursue three objectives: 1) to contribute with new key theoretical methods and results, 2) to develop the corresponding numerical tools, and 3) to build up new computational software, the DYCON-COMP computational platform, thereby bridging the gap to applications. The field of PDEs, together with numerical approximation and simulation methods and control theory, have evolved significantly in the last decades in a cross-fertilization process, to address the challenging demands of industrial and cross-disciplinary applications such as, for instance, the management of natural resources, meteorology, aeronautics, oil industry, biomedicine, human and animal collective behaviour, etc. Despite these efforts, some of the key issues still remain unsolved, either because of a lack of analytical understanding, of the absence of efficient numerical solvers, or of a combination of both. This project identifies and focuses on six key topics that play a central role in most of the processes arising in applications, but which are still poorly understood: control of parameter dependent problems; long time horizon control; control under constraints; inverse design of time-irreversible models; memory models and hybrid PDE/ODE models, and finite versus infinite-dimensional dynamical systems. These topics cannot be handled by superposing the state of the art in the various disciplines, due to the unexpected interactive phenomena that may emerge, for instance, in the fine numerical approximation of control problems. The coordinated and focused effort that we aim at developing is timely and much needed in order to solve these issues and bridge the gap from modelling to control, computer simulations and applications.

2 065 125 €

Start date: 2016-10-01, End date: 2021-09-30

The aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptive penetrating peptides (adaptamers) for targeted delivery. It is known that the recently developed therapeutic technologies (i.e. gene therapy, chemotherapy, hyperthermia, etc.) cannot reach their expected potential due to limitations in the current delivery strategies, which hinder the efficient targeting of the appropriate tissues, cells and organelles. Despite the enormous therapeutic potential of short penetrating peptides, these molecules suffer from drawbacks such as toxicity, instability to protease digestion and lack of specificity. Dynamic covalent chemistry has significant synthetic advantages. In the proposed research, peptide scaffolds with clickable reversible groups (e.g. hydrazide) will be conjugated with collections of aldehydes to afford self-adaptive biomimetic transporters, whose secondary structure and penetrating properties will be systematically characterized by biophysical, cell-biology and pattern recognition techniques. The versatility of dynamic supramolecular “peptide adaptamers” with precisely positioned protein ligands will be explored for multivalent specific recognition, protein transport, cell targeting of drugs and probes and membrane epitoping. Additionally, we propose to synthesise dynamic and environmentally sensitive fluorescent probes for biocompatible membrane labelling and uptake signalling. The resulting discoveries of this research will allow the formulation of novel transfecting reagents for gene therapy, selective platforms for drug-delivery and the development of dynamic fluorescent membrane probes. The potential results of this proposal will shake the fields of drug-delivery and non-viral gene transfection and will resolve the limitations of the current approaches.

1 492 525 €

Start date: 2016-02-01, End date: 2021-01-31

More than 250 years after establishing the electrical nature of the lightning flash, we still do not understand how a lightning channel advances. Most of these channels progress not continuously but in a series of sudden jumps and, as they jump, they emit bursts of energetic radiation. Despite increasingly accurate observations, there is no accepted explanation for this stepped progression. This proposal addresses this open question. First, we propose a methodological breakthrough that will allow us to tackle the main bottleneck in the theoretical understanding of lightning: the wide disparity between length-scales within a lightning flash. We plan to apply techniques that have succeeded in other fields, such as multi-model coupled simulations and moving-mesh finite elements methods. Acting as a computational microscope, these techniques will reveal the small-scale electrodynamics around a lightning channel. We will then apply these techniques to elucidate the intertwined problems of lightning channel stepping and thunderstorm-related high-energy emissions. The main hypothesis that we will test is that stepping is due to the formation of low-conductivity spots within the filamentary-discharge region that surrounds a lightning channel. This idea is motivated by observations from high-altitude atmospheric discharges. By resolving the small-scale dynamics, with our numerical method, we will also test hypothesis for high-energy emissions from the lighting channel, which crucially depend on the microscopic distribution of electric fields. This interdisciplinary proposal, straddling between geophysics and gas discharge physics, seeks a double breakthrough: the methodological one of building multi-scale lightning simulations and the hypothesis-driven one of finding out the reason for stepping. If it succeeds, it will achieve a leap forward in our knowledge of lightning, undoubtedly one of the greatest spectacles in our planet's repertoire.

1 960 826 €

Start date: 2016-06-01, End date: 2021-05-31

"The Environmental Justice Atlas (www.ejatlas.org) is a global database built by us, drawing on activist and academic knowledge. It maps 1500 conflicts. To improve geographical and thematic coverage it will grow to 3000 by 2019. It systematizes conflicts across 100+ fields documenting the commodities at stake, the actors involved, impacts, forms of mobilizations and outcomes allowing analyses that will lead to a general theory of ecological distribution conflicts. We shall research the links between changes in social metabolism and resource extraction conflicts at the “commodity frontiers”. Also other questions in political ecology and social movement theory such as the effectiveness of direct action by grassroots protesters compared to institutional forms of contention. Does the involvement of different actors, e.g. indigenous groups, relate to different conflict outcomes? How often does the IUCN ally itself to ""the environmentalism of the poor""? Do mobilizations and outcomes vary across sectors (mining, hydroelectric dams, waste incinerators) according to project differences in economic and biophysical dimensions, environmental and health risks? Are conflicts on point resources (mining, oil extraction) regularly different from conflicts in agriculture? Can we track networked resistances against Western companies, compared to those from China or other countries? Resistance to environmental damage has brought into being many local and some international EJOs pushing for alternative social transformations. We shall study the Vocabulary of Environmental Justice they deploy: climate justice, water justice, food sovereignty, biopiracy, sacrifice zones, and other terms specific to countries: Chinese “cancer villages”, Indian “sand mafias”, Brazilian “green deserts” (eucalyptus plantations). Finally, are there signs of an alliance between the Global Environmental Justice Movement and the small European movement for “prosperity without growth”, décroissance, Post-Wachstum?"

1 910 811 €

Start date: 2016-06-01, End date: 2021-05-31

The last decade has witnessed a new spring for dynamical systems. The field - initiated by Poincare in the study of the N-body problem - has become essential in the understanding of seemingly far off fields such as combinatorics, number theory and theoretical computer science. In particular, ideas from ergodic theory played an important role in the resolution of long standing open problems in combinatorics and number theory. A striking example is the role of dynamics on nilmanifolds in the recent proof of Hardy-Littlewood estimates for the number of solutions to systems of linear equations of finite complexity in the prime numbers. The interplay between ergodic theory, number theory and additive combinatorics has proved very fruitful; it is a fast growing area in mathematics attracting many young researchers. We propose to tackle central open problems in the area.

1 342 500 €

Start date: 2016-05-01, End date: 2021-04-30

"UN-Water has recently warned that in only ten years' time, by 2025, water scarcity will be affecting 1.8 billion people, with two-thirds of the world population possibly living under conditions of water stress. There exists, hence, a strong need to rigorously manage drinking water resources. The production of potable water by membrane water treatment systems is relatively economic and benign. 80 million m3 of potable water are already produced nowadays using membranes. However, the efficiency of membrane water treatment processes may severely be impeded by a phenomenon known as "membrane fouling". Hereby, organic matter present in the water to be treated adsorbs on the surface of the porous membrane filters, resulting in the build-up of a surface layer which then increasingly closes the membrane pores and, hence, dramatically diminishes the potable water production. If detected at an early stage, such fouling could be counteracted by adequate process operating conditions. Once a rigid fouling layer is formed, however, chemically aggressive membrane cleaning procedures need to be employed with respective negative environmental impact. ESSENS proposes a monitoring device that outperforms existing fouling detection techniques and allows optimizing both fouling prevention and membrane cleaning cycles. The result is a significantly more efficient and sustainable membrane water treatment processes, enabling a greatly improved management of the drinking water production."

149 760 €

Start date: 2016-10-01, End date: 2018-03-31

As a result of the research undertaken in the NANOFORCELLS project (ERC-StG-2011-278860), Dr Montserrat Calleja’s team has successfully developed instrumentation for the investigation of cell mechanics. The NANOFORCELLS project proposes a tool-box of three converging technologies for the aim of discriminating cancer and healthy cells from their physical properties: AFM, label-free microscopy and nanomechanical sensors. The instrument object of commercialization through the FAST-SPECTRO project is the output of the second key technology development: label-free microscopy. The research undertaken under ERC support has evidenced that cell lines with different degrees of tumorigenicity show different mechanical properties, a result confirmed by AFM and nanomechanical tests. Such results are found to have a potential interest for cancer diagnostics, We envision a high commercial potential of the technique. In order to accelerate the market entry of the results, the FAST SPECTRO “Proof of Concept” (PoC) project will focus on conducting a market feasibility study of the SMS instrument developed, as well as clarifying the IP position strategy and making an initial approach to potential partners and investors.

149 922 €

Start date: 2015-11-01, End date: 2017-04-30

Anomalies in surface temperatures, winds, and precipitation can significantly alter energy supply and demand, cause flooding, and cripple transportation networks. Better management of these impacts can be achieved by extending the duration of reliable predictions of the atmospheric circulation. Polar stratospheric variability can impact surface weather for well over a month, and this proposed research presents a novel approach towards understanding the fundamentals of how this coupling occurs. Specifically, we are interested in: 1) how predictable are anomalies in the stratospheric circulation? 2) why do only some stratospheric events modify surface weather? and 3) what is the mechanism whereby stratospheric anomalies reach the surface? While this last question may appear academic, several studies indicate that stratosphere-troposphere coupling drives the midlatitude tropospheric response to climate change; therefore, a clearer understanding of the mechanisms will aid in the interpretation of the upcoming changes in the surface climate. I propose a multi-pronged effort aimed at addressing these questions and improving monthly forecasting. First, carefully designed modelling experiments using a novel modelling framework will be used to clarify how, and under what conditions, stratospheric variability couples to tropospheric variability. Second, novel linkages between variability external to the stratospheric polar vortex and the stratospheric polar vortex will be pursued, thus improving our ability to forecast polar vortex variability itself. To these ends, my group will develop 1) an analytic model for Rossby wave propagation on the sphere, and 2) a simplified general circulation model, which captures the essential processes underlying stratosphere-troposphere coupling. By combining output from the new models, observational data, and output from comprehensive climate models, the connections between the stratosphere and surface climate will be elucidated.

1 808 000 €

Start date: 2016-05-01, End date: 2021-04-30

Plants evolved a unique molecular mechanism that spatially regulate auxin, forming finely tuned gradients and local maxima of auxin that inform and direct developmental patterning and adaptive growth processes. Recent findings call into question the uniqueness of polar auxin transport in the sense that more plant hormones seem to be actively transported. Although still lacking many mechanistic details, as well as comprehensive functional connotations, these findings warrant a more thorough investigation into the prospect of a broader scope for plants spatial regulation capacity in the context of additional hormones. Critically, we lack an effective set of tools to directly investigate and dissect the particulars of plant hormones mobility at the molecular level. My long-term goal is to provide a molecular and mechanistic understanding of plant hormones dynamics that will augment our evolving model of how they are regulated and how they convey information. Here, I hypothesize that GA mobility in plants is controlled and directed by an active transport mechanism to form distinct distribution patterns that affect signaling. I will test my hypothesis with a multi-faceted and multi-disciplinary approach, combining: fluorescent labeling of key gibberellins to map their accumulation sites in whole plants and at the sub-cellular level; chemical-biology strategies that facilitate manipulation of GA “origin point” in planta to map and quantify GA flow pathways; probe-based genetic screens and un-biased photo-affinity labeling to identify proteins affecting GA mobility; and genetic and molecular biology techniques to characterize identified proteins’ functions. I expect to offer an exceptional, detailed view into the inner workings of gibberellins dynamics in planta and into the mechanisms driving it. I further anticipate that the strategies developed here to specifically address gibberellins could be straightforwardly re-tailored to investigate additional plant hormones.

1 500 000 €

Start date: 2016-02-01, End date: 2021-01-31

In the last decade the approaches of the global history have been emphasized in order to visualize the progress, form and method which historians have undertaken when carrying out ambitious research projects to analyse and compare diverse geographical and cultural areas of Asia and Europe. But when dealing with comparisons and cross-cultural studies in Europe and Asia, some scholarly works have exceeded of ambiguities when defining geographical units as well as chronology. In this project I examine perceptions and dialogues between China and Europe by analysing strategic geopolitical sites which fostered commerce, consumption and socioeconomic networks between China and Europe through a particular case study: Macau, connecting with South China, and Marseille in Mediterranean Europe. How did foreign merchant networks and trans-national communities of Macau and Marseille operate during the eighteenth century and contribute to somehow transfer respectively European and Chinese socio-cultural habits and forms in local population? What was the degree and channels of consumption of European goods in China and Chinese goods in Europe? These are the main questions to answer during my research to explore the bilateral Sino-European trade relations and how the trans-national dimension of exotic commodities changed tastes by creating a new type of global consumerism. Such concrete comparison can help to narrow the gap that some researchers have created when widely analysing differences between Asia and Europe without a specific geographical and chronological delineation. The major novelty of this project is based on the use of Chinese and European sources to study changes in consumer behaviour. The principal investigator of the project works in China which is and added value for the achievement of outstanding results. So the expected results will bring an obvious breakthrough by adding the specific part of the project in which each team member will work.

1 499 625 €

Start date: 2016-07-01, End date: 2021-06-30

In order to fully understand the complexity of biological processes that are reflected by simultaneous occurrences of intra and inter-cellular events, multiplexed imaging platforms are needed. Fluorescent reporter genes, with their “multicolor” imaging capabilities, have revolutionized science and their founders have been awarded the Nobel Prize. Nevertheless, the light signal source of these reporters, which restricts their use in deep tissues and in large animals (and potentially in humans), calls for alternatives. Reporter genes for MRI, although in their infancy, showed several exceptionalities, including the ability to longitudinal study the same subject with unlimited tissue penetration and to coregister information from reporter gene expression with high-resolution anatomical images. Inspired by the multicolor capabilities of optical reporter genes, this proposal aims to develop, optimize, and implement genetically engineered reporter systems for MRI with artificial “multicolor” characteristics. Capitalizing on (i) the Chemical Exchange Saturation Transfer (CEST)-MRI contrast mechanism that allows the use of small bioorganic molecules as MRI sensors, (ii) the frequency encoding, color-like features of CEST, and on (iii) enzyme engineering procedures that allow the optimization of enzymatic activity for a desired substrate, a “multicolor” genetically encoded MRI reporter system is proposed. By (a) synthesizing libraries of non-natural nucleosides (“reporter probes”) to generate artificially “colored” CEST contrast, and (b) performing directed evolution of deoxyribonucleoside kinase (dNK) enzymes (“reporter genes”) to phosphorylate those nucleosides, the “multicolor” genetically encoded MRI “reporter system” will be created. The orthogonally of the obtained pairs of substrate (CEST sensor)/ enzyme (mutant dNK) will allow their simultaneous use as a genetically encoded reporter system for in vivo “multicolor” monitoring of reporter gene expression with MRI.

1 478 284 €

Start date: 2016-05-01, End date: 2021-04-30

How animals make decisions in the wild is an open key-question in biology. Our lack of knowledge results from a technological gap – the difficulty to track animals over long periods while monitoring their behaviour; and from a conceptual gap – how to identify animals’ decision-points outdoors? We suggest applying our innovative on-board miniature sensors, to study decision making in the wild. We focus on one of the most fundamental contexts of decision making – foraging for food. We will study bats, which constitute over 20% of mammalian species and are extremely diverse, enabling to examine different aspects of decision making. Importantly, echolocating bats emit sound to perceive their environment, allowing us to infer their behavior (attacks on prey and interactions with conspecifics) via sound recording. Our miniature sensors include a GPS and an ultrasonic microphone, which enables us to reveal not only bats’ movements, but also their behavior and accordingly the factors underlying their decisions. We will study three bat species to elucidate different aspects of foraging decisions: (1) How does animal sociality facilitate decision making? We have developed a system to monitor an entire colony including all conspecific-interactions when bats are in the roost or foraging outside. (2) How do animals weigh current input against previous experience? We will study a bat that must nightly search large areas over sea to find food. (3) How flexible are animal decisions? We will manipulate the natural environment of specific individuals to study how they adjust their foraging. Our results will have far-reaching implications in many fields, from animal conservation to robotics. The operational and technical difficulty of performing controlled manipulations in the wild drives most disciplines to perform experiments exclusively in artificial laboratory conditions. Our approach opens new opportunities to conduct controlled studies in the natural environment.

1 928 750 €

Start date: 2016-03-01, End date: 2021-02-28