ERC FUNDED PROJECTS

"We propose to study different questions in the area of the so called geometric analysis. Most of the topics we are interested in deal with the connection between the behavior of singular integrals and the geometry of sets and measures. The study of this connection has been shown to be extremely helpful in the solution of certain long standing problems in the last years, such as the solution of the Painlev\'e problem or the obtaining of the optimal distortion bounds for quasiconformal mappings by Astala. More specifically, we would like to study the relationship between the L^2 boundedness of singular integrals associated with Riesz and other related kernels, and rectifiability and other geometric notions. The so called David-Semmes problem is probably the main open problem in this area. Up to now, the techniques used to deal with this problem come from multiscale analysis and involve ideas from Littlewood-Paley theory and quantitative techniques of rectifiability. We propose to apply new ideas that combine variational arguments with other techniques which have connections with mass transportation. Further, we think that it is worth to explore in more detail the connection among mass transportation, singular integrals, and uniform rectifiability. We are also interested in the field of quasiconformal mappings. We plan to study a problem regarding the quasiconformal distortion of quasicircles. This problem consists in proving that the bounds obtained recently by S. Smirnov on the dimension of K-quasicircles are optimal. We want to apply techniques from quantitative geometric measure theory to deal with this question. Another question that we intend to explore lies in the interplay of harmonic analysis, geometric measure theory and partial differential equations. This concerns an old problem on the unique continuation of harmonic functions at the boundary open C^1 or Lipschitz domain. All the results known by now deal with smoother Dini domains."

1 105 930 €

Start date: 2013-05-01, End date: 2018-04-30

The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.

2 422 271 €

Start date: 2013-05-01, End date: 2019-04-30

Pregnancy involves biological adaptations that are necessary for the onset, maintenance and regulation of maternal behavior. We were the first group to find (1, 2) that pregnancy is associated with consistent, pronounced and long-lasting reductions in cerebral gray matter (GM) volume in areas of the social-cognition network. The aim of BEMOTHER is to develop an integrative model of the adaptations for motherhood that occur during pregnancy and the postpartum period by: i) establishing when the brain of pregnant women begins to change and how it evolves; ii) characterizing the dynamics of cognitive performance, theory-of-mind, maternal-infant bonding and psychiatric measures; iii) assessing the effect of environmental and/or psychological factors in the maternal adaptations, iv) identifying the metabolomics biomarkers associated with maternal adaptations, and v) integrating the previous findings within the Research Domain Criteria framework (RDoC) (3). We will use a prospective longitudinal design at 5 time points (1 pre-pregnancy session, 2 intra-pregnancy sessions and 2 postpartum sessions) during which neuroimaging, psychological, behavioral and metabolomics data will be acquired in 3 groups of women: a group of nulliparous women who will be undergoing a full-term pregnancy, another group of nulliparous women whose same-sex partners will undergo a full-term pregnancy, and a group of control nulliparous women. We will provide the longitudinal RDoC-based model at the end of the study, but we will also deliver intermediate longitudinal evaluations after the postpartum session, as well as cross-sectional analyses after the first intra-pregnancy session and the postpartum session. BEMOTHER is timely and innovative. It adopts the translational RDoC framework in order to provide a pioneering, comprehensive and dynamic characterization of the adaptations for motherhood, addressing the interaction among different functional domains at different levels of analysis.

2 465 131 €

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

BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways

2 290 046 €

Start date: 2009-04-01, End date: 2014-03-31

Despite intense research efforts in almost every branch of the natural sciences, cancer continues to be one of the leading causes of death worldwide. It is thus remarkable that little or no therapeutic use has been made of a whole discipline, heterogeneous catalysis, which is noted for its specificity and for enabling chemical reactions in otherwise passive environments. At least in part, this could be attributed to practical difficulties: the selective delivery of a catalyst to a tumour and the remote activation of its catalytic function only after it has reached its target are highly challenging objectives. Only recently, the necessary tools to overcome these problems seem within reach. CADENCE aims for a breakthrough in cancer therapy by developing a new therapeutic concept. The central hypothesis is that a growing tumour can be treated as a special type of reactor in which reaction conditions can be tailored to achieve two objectives: i) molecules essential to tumour growth are locally depleted and ii) toxic, short-lived products are generated in situ. To implement this novel approach we will make use of core concepts of reactor engineering (kinetics, heat and mass transfer, catalyst design), as well as of ideas borrowed from other areas, mainly those of bio-orthogonal chemistry and controlled drug delivery. We will explore two different strategies (classical EPR effect and stem cells as Trojan Horses) to deliver optimized catalysts to the tumour. Once the catalysts have reached the tumour they will be remotely activated using near-infrared (NIR) light, that affords the highest penetration into body tissues. This is an ambitious project, addressing all the key steps from catalyst design to in vivo studies. Given the novel perspective provided by CADENCE, even partial success in any of the approaches to be tested would have a significant impact on the therapeutic toolbox available to treat cancer.

2 483 136 €

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

"Understanding the nature of consciousness is one of the grand outstanding scientific challenges and two of its features stand out: consciousness is defined as the construction of one coherent scene but this scene is experienced with a delay relative to the action of the agent and not necessarily the cause of actions and thoughts. Did evolution render solutions to the challenge of survival that includes epiphenomenal processes? The Conscious Distributed Adaptive Control (CDAC) project aims at resolving this paradox by using a multi-disciplinary approach to show the functional role of consciousness in adaptive behaviour, to identify its underlying neuronal principles and to construct a neuromorphic robot based real-time conscious architecture. CDAC proposes that the shift from surviving in a physical world to one that is dominated by intentional agents requires radically different control architectures combining parallel and distributed control loops to assure real-time operation together with a second level of control that assures coherence through sequential coherent representation of self and the task domain, i.e. consciousness. This conscious scene is driving dedicated credit assignment and planning beyond the immediately given information. CDAC advances a comprehensive framework progressing beyond the state of the art and will be realized using system level models of a conscious architecture, detailed computational studies of its underlying neuronal substrate focusing, empirical validation with a humanoid robot and stroke patients and the advancement of beyond state of the art tools appropriate to the complexity of its objectives. The CDAC project directly addresses one of the main outstanding questions in science: the function and genesis of consciousness and will advance our understanding of mind and brain, provide radically new neurorehabilitation technologies and contribute to realizing a new generation of robots with advanced social competence."

2 469 268 €

Start date: 2014-02-01, End date: 2019-01-31

"Our research group has worked over the years at the interface between cancer and ageing, with a strong emphasis on mouse models. More recently, we became interested in cellular reprogramming because we hypothesized that understanding cellular plasticity could yield new insights into cancer and ageing. Indeed, during the previous ERC Advanced Grant, we made relevant contributions to the fields of cellular reprogramming (Nature 2013), cellular senescence (Cell 2013), cancer (Cancer Cell 2012), and ageing (Cell Metabolism 2012). Now, we take advantage of our diverse background and integrate the above processes. Our unifying hypothesis is that cellular plasticity lies at the basis of tissue regeneration (“adaptive cellular plasticity”), as well as at the origin of cancer (“maladaptive gain of cellular plasticity”) and ageing (“maladaptive loss of cellular plasticity”). A key experimental system will be our “reprogrammable mice” (with inducible expression of the four Yamanaka factors), which we regard as a tool to induce cellular plasticity in vivo. The project is divided as follows: Objective #1 – Cellular plasticity and cancer: role of tumour suppressors in in vivo de-differentiation and reprogramming / impact of transient de-differentiation on tumour initiation / lineage tracing of Oct4 to determine whether a transient pluripotent-state occurs during cancer. Objective #2 – Cellular plasticity in tissue regeneration and ageing: impact of transient de-differentiation on tissue regeneration / contribution of the damage-induced microenvironment to tissue regeneration / impact of transient de-differentiation on ageing. Objective #3: New frontiers in cellular plasticity: chemical manipulation of cellular plasticity in vivo / new states of pluripotency / characterization of in vivo induced pluripotency and its unique properties. We anticipate that the completion of this project will yield new fundamental insights into cancer, regeneration and ageing."

2 488 850 €

Start date: 2015-10-01, End date: 2021-09-30

There is a fast-growing interest in extending the capabilities of computing systems to perform human-like tasks in an intelligent way. These technologies are usually referred to as cognitive computing. We envision a next revolution in computing in the forthcoming years that will be driven by deploying many “intelligent” devices around us in all kind of environments (work, entertainment, transportation, health care, etc.) backed up by “intelligent” servers in the cloud. These cognitive computing systems will provide new user experiences by delivering new services or improving the operational efficiency of existing ones, and altogether will enrich our lives and our economy. A key characteristic of cognitive computing systems will be their capability to process in real time large amounts of data coming from audio and vision devices, and other type of sensors. This will demand a very high computing power but at the same time an extremely low energy consumption. This very challenging energy-efficiency requirement is a sine qua non to success not only for mobile and wearable systems, where power dissipation and cost budgets are very low, but also for large data centers where energy consumption is a main component of the total cost of ownership. Current processor architectures (including general-purpose cores and GPUs) are not a good fit for this type of systems since they keep the same basic organization as early computers, which were mainly optimized for “number crunching”. CoCoUnit will take a disruptive direction by investigating unconventional architectures that can offer orders of magnitude better efficiency in terms of performance per energy and cost for cognitive computing tasks. The ultimate goal of this project is to devise a novel processing unit that will be integrated with the existing units of a processor (general-purpose cores and GPUs) and altogether will be able to deliver cognitive computing user experiences with extremely high energy-efficiency.

2 498 661 €

Start date: 2019-09-01, End date: 2025-02-28

Current IT research does not respond to the world's multi-cultural reality. It could be argued that we are imposing the paradigms of our market-driven western culture also on IT and that current IT research results will only facilitate the access of a small part of the world’s information to a small part of the world's population. Most IT research is being carried out with a western centred approach and as a result, our data models, cognition models, user models, interaction models, ontologies, … are all culturally biased. This fact is quite evident in music information research, since, despite the world's richness in musical cultures, most of the research is centred on CDs and metadata of our western commercial music. CompMusic wants to break this huge research bias. By approaching musical information modelling from a multicultural perspective it aims at advancing our state of the art while facilitating the discovery and reuse of the music produced outside the western commercial context. But the development of computational models to address the world’s music information richness cannot be done from the West looking out; we have to involve researchers and musical experts immersed in the different cultures. Their contribution is fundamental to develop the appropriate multicultural musicological and cognitive frameworks from which we should then carry our research on finding appropriate musical features, ontologies, data representations, user interfaces and user centred approaches. CompMusic will investigate some of the most consolidated non-western classical music traditions, Indian (hindustani, carnatic), Turkish-Arab (ottoman, andalusian), and Chinese (han), developing the needed computational models to bring their music into the current globalized information framework. Using these music cultures as case studies, cultures that are alive and have a strong influence in current society, we can develop rich information models that can take advantage of the existing information coming from musicological and cultural studies, from mature performance practice traditions and from active social contexts. With this approach we aim at challenging the current western centred information paradigms, advance our IT research, and contribute to our rich multicultural society.

2 443 200 €

Start date: 2011-07-01, End date: 2017-06-30