ERC FUNDED PROJECTS

"Understanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamics of growth regulatory networks, essentially because leaf development is a linear system with cell division at the leaf basis followed by cell expansion and maturation. Furthermore, the growth zone is relatively large allowing easy access of tissues at different positions. Four different perturbations of maize leaf size will be analyzed with cellular resolution: wild-type and plants having larger leaves (as a consequence of GA20OX1 overexpression), both grown under either well-watered or mild drought conditions. Firstly, a 3D cellular map of the growth zone of the fourth leaf will be made. RNA-SEQ of three different tissues (adaxial- and abaxial epidermis; mesophyll) obtained by laser dissection with an interval of 2.5 mm along the growth zone will allow for the analysis of the transcriptome with high resolution. Additionally, the composition of fifty selected growth regulatory protein complexes and DNA targets of transcription factors will be determined with an interval of 5 mm along the growth zone. Computational methods will be used to construct comprehensive integrative maps of the cellular and molecular processes occurring along the growth zone. Finally, selected regulatory nodes of the growth regulatory networks will be further functionally analyzed using a transactivation system in maize. AMAIZE opens up new perspectives for the identification of optimal growth regulatory networks that can be selected for by advanced breeding or for which more robust variants (e.g. reduced susceptibility to drought) can be obtained through genetic engineering. The ability to improve the growth of maize and in analogy other cereals could have a high impact in providing food security"

2 418 429 €

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

"The proposed research project seeks to further our understanding on two important questions for the design of monetary policy: (a) What are the effects of monetary policy interventions on asset price bubbles? (b) How should monetary policy be conducted in the presence of asset price bubbles? The first part of the project will focus on the development of a theoretical framework that can be used to analyze rigorously the implications of alternative monetary policy rules in the presence of asset price bubbles, and to characterize the optimal monetary policy. In particular, I plan to use such a framework to assess the merits of a “leaning against the wind” strategy, which calls for a systematic rise in interest rates in response to the development of a bubble. The second part of the project will seek to produce evidence, both empirical and experimental, regarding the effects of monetary policy on asset price bubbles. The empirical evidence will seek to identify and estimate the sign and response of asset price bubbles to interest rate changes, exploiting the potential differences in the joint behavior of interest rates and asset prices during “bubbly” episodes, in comparison to “normal” times. In addition, I plan to conduct some lab experiments in order to shed some light on the link between monetary policy and bubbles. Participants will trade two assets, a one-period riskless asset and a long-lived stock, in an environment consistent with the existence of asset price bubbles in equilibrium. Monetary policy interventions will take the form of changes in the short-term interest rate, engineered by the experimenter. The experiments will allow us to evaluate some of the predictions of the theoretical models regarding the impact of monetary policy on the dynamics of bubbles, as well as the effectiveness of “leaning against the wind” policies."

799 200 €

Start date: 2014-01-01, End date: 2017-12-31

Whole genome sequencing is quickly becoming a routine clinical instrument. However, our ability to decipher DNA variants is still largely limited to protein-coding exons, which comprise 1% of the genome. Most known Mendelian mutations are in exons, yet genetic testing still fails to show causal coding mutations in more than 50% of well-characterized Mendelian disorders. This defines a pressing need to interpret noncoding genome sequences, and to establish the role of noncoding mutations in Mendelian disease. A recent case study harnessed whole genome sequencing, epigenomics, and functional genomics to show that mutations in an enhancer cause most cases of neonatal diabetes due to pancreas agenesis. This example raises major questions: (i) what is the overall impact of penetrant regulatory mutations in human diabetes? (ii) do regulatory mutations cause distinct forms of diabetes? (iii) more generally, can we develop a strategy to systematically tackle regulatory variation in Mendelian disease? The current project will address these questions with unique resources. First, we have created epigenomic and functional perturbation resources to interpret the regulatory genome in embryonic pancreas and adult pancreatic islets. Second, we have collected an unprecedented international cohort of patients with a phenotype consistent with monogenic diabetes, yet lacking mutations in known gene culprits after genetic testing, and therefore with increased likelihood of harboring noncoding mutations. Third, we have developed a prototype platform to sequence regulatory mutations in a large number of patients. These resources will be combined with innovative strategies to uncover causal enhancer mutations underlying Mendelian diabetes. If successful, this project will expand the diagnostic spectrum of diabetes, it will discover new genetic regulators of diabetes-relevant networks, and will provide a framework to understand regulatory variation in Mendelian disease.

2 243 746 €

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

This project aims to reformulate and generalize standard theories of human health and mortality. It proposes new formal models and a systematic agenda to empirically test hypotheses that link developmental biology, epigenetics and adult human illness, disability and mortality. We seek to break new ground developing innovative formal models for illnesses and mortality, testing new hypotheses about the evolution of human health and, to the extent permitted by findings, reformulating standard theories to make them applicable to a less restrictive segment of populations than they are now. Over the past two decades there has been massive growth of research on the nature of delayed adult effects of conditions experienced in early life. This field of research is known as the Developmental Origins of Adult Health and Disease (DOHaD). Increasing evidence suggests that the mechanisms that are implicated are epigenetic and constitute an evolved adaptation selected over thousands of years to improve fitness in changing landscapes. The emergence of DOHaD is as close as we will ever come to a paradigmatic shift in the study of human health, disability and mortality. The most tantalizing possibility is that advances in our understanding of epigenetic mechanisms will shed light on pathways linking early exposures and delayed adult health thus fundamentally transforming our understanding of human illnesses and, in one fell swoop, bridge population health, epigenetics, and developmental and evolutionary biology. The overarching goal of this project is to contribute to this nascent area of study by (a) proposing new formal demographic models of health, disability and mortality; (b) empirically testing DOHaD predictions with population data; (c) testing a microsimulation model to verify DOHaD predictions about two conditions, obesity and Type 2 Diabetes, and (d) assessing the adult health, disability and mortality toll implicated by relations between early conditions, obesity and T2D.

2 852 655 €

Start date: 2019-03-01, End date: 2024-02-29

With eNANO I will introduce a disruptive approach toward controlling and understanding the dynamical response of material nanostructures, expanding nanoscience and nanotechnology in unprecedented directions. Specifically, I intend to inaugurate the field of free-electron nanoelectronics, whereby electrons evolving in the vacuum regions defined by nanostructures will be generated, guided, and sampled at the nanoscale, thus acting as probes to excite, detect, image, and spectrally resolve polaritonic modes (e.g., plasmons, optical phonons, and excitons) with atomic precision over sub-femtosecond timescales. I will exploit the wave nature of electrons, extending the principles of nanophotonics from photons to electrons, therefore gaining in spatial resolution (by relying on the large reduction in wavelength) and strength of interaction (mediated by Coulomb fields, which in contrast to photons render nonlinear interactions ubiquitous when using free electrons). I will develop the theoretical and computational tools required to investigate this unexplored scenario, covering a wide range of free-electron energies, their elastic interactions with the material atomic structures, and their inelastic coupling to nanoscale dynamical excitations. Equipped with these techniques, I will further address four challenges of major scientific interest: (i) the fundamental limits to the space, time, and energy resolutions achievable with free electrons; (ii) the foundations and feasibility of pump-probe spectral microscopy at the single-electron level; (iii) the exploration of quantum-optics phenomena by means of free electrons; and (iv) the unique perspectives and potential offered by vertically confined free-electrons in 2D crystals. I will face these research frontiers by combining knowledge from different areas through a multidisciplinary theory group, in close collaboration with leading experimentalists, pursuing a radically new approach to study and control the nanoworld.

1 899 788 €

Start date: 2018-12-01, End date: 2023-11-30

The goal of this project is to pursue new methods in the mathematical analysis of non-local and non-linear partial differential equations. For this purpose we present several physical scenarios of interest in the context of incompressible fluids, from a mathematical point of view as well as for its applications: both from the standpoint of global well-posedness, existence and uniqueness of weak solutions and as candidates for blowup. The equations we consider are the incompressible Euler equations, incompressible porous media equation and the generalized Quasi-geostrophic equation. This research will lead to a deeper understanding of the nature of the set of initial data that develops finite time singularities as well as those solutions that exist for all time for incompressible flows.

1 779 369 €

Start date: 2018-09-01, End date: 2023-08-31

"Industrial organization has been influential in shaping our understanding of how firms behave in markets, and also Most of the industrial organization literature is based on the premise that firms are represented by a single decision maker, who is driven by a motive of profit maximization and cost minimization. This assumption is nowadays becoming a constraint on IO theory, preventing it from being able to explain certain observed empirical regularities. For instance, it has been well documented that seemingly identical firms often exhibit differing performance or productivity. Under the existing paradigm, this should not occur, since identical firms should choose the same cost-minimizing technology. The goal of this proposal is to develop a new IO theory based on a richer view of the firm, one in which non-trivial conflicts of interest among shareholders, workers, managers and consumers will shape firm boundaries. This ""Organizational Industrial Organization'' (OIO) will generate rich new insights for the positive and normative analysis of industries, whether or not firms in these industries have market power. In particular, it will be able to account for heterogeneity in organizations among identical firms, will provide simple explanations for real world examples that would be difficult to understand in the traditional IO setting, but also bring fresh and novel analysis to traditional IO questions like the scale and scope of firms, the dynamics of merger activity, and also to less traditional questions like the roles of the managerial market, finance or corporate governance for industry performance. This proposal details three work packages that the team will develop in priority in this project: - Finance, governance, the managerial market and firm boundaries. - The dynamics of firm boundaries and delegation. - Market power, scale and scope"

1 382 264 €

Start date: 2015-01-01, End date: 2019-12-31

RADICAL explores the idea that consciousness is something that the brain learns to do rather than a static property of certain neural states vs. others. Here, considering that consciousness is extended both in space and in time, I adopt a resolutely dynamical perspective that mandates an experimental approach focused on change, at different time scales. I suggest that consciousness arises as a result of the brain's continuous attempts at predicting not only the consequences of its actions on the world and on other agents, but also the consequences of activity in one cerebral region on activity in other regions. By this account, the brain continuously and unconsciously learns to redescribe its own activity to itself, so developing systems of metarepresentations that characterise and qualify the target first order representations. Such learned redescriptions form the basis of conscious experience. Learning and plasticity are thus constitutive of consciousness. This is what I call the “Radical Plasticity Thesis”. In a sense, this is the enactive perspective, but turned both inwards and (further) outwards. Consciousness involves “signal detection on the mind”; the conscious mind is the brain's (non-conceptual, implicit) theory about itself. Theoretically, RADICAL offers the possibility of unifying Global Workspace Theory with higher-order Thought Theory by showing how the former can be built through mechanisms that flesh out the latter. Empirically, RADICAL aims at testing these ideas in three domains: (1) the perception action loop, (2) the self-other loop, and (3) the inner loop. 20 experiments leveraging behavioural experimentation, brain imaging, and computational modeling are proposed to test and further develop RADICAL. The overarching goal of the project is to characterize the computational principles that differentiate conscious from unconscious cognition, based on a bold, original, and innovative theory in which learning and plasticity play central roles.

2 286 316 €

Start date: 2014-05-01, End date: 2019-04-30