ERC FUNDED PROJECTS

Learning to read is probably one of the most exciting discoveries in our life. Using a longitudinal approach, the research proposed examines how the human brain responds to two major challenges: (a) the instantiation a complex cognitive function for which there is no genetic blueprint (learning to read in a first language, L1), and (b) the accommodation to new statistical regularities when learning to read in a second language (L2). The aim of the present research project is to identify the neural substrates of the reading process and its constituent cognitive components, with specific attention to individual differences and reading disabilities; as well as to investigate the relationship between specific cognitive functions and the changes in neural activity that take place in the course of learning to read in L1 and in L2. The project will employ a longitudinal design. We will recruit children before they learn to read in L1 and in L2 and track reading development with both cognitive and neuroimaging measures over 24 months. The findings from this project will provide a deeper understanding of (a) how general neurocognitive factors and language specific factors underlie individual differences – and reading disabilities– in reading acquisition in L1 and in L2; (b) how the neuro-cognitive circuitry changes and brain mechanisms synchronize while instantiating reading in L1 and in L2; (c) what the limitations and the extent of brain plasticity are in young readers. An interdisciplinary and multi-methodological approach is one of the keys to success of the present project, along with strong theory-driven investigation. By combining both we will generate breakthroughs to advance our understanding of how literacy in L1 and in L2 is acquired and mastered. The research proposed will also lay the foundations for more applied investigations of best practice in teaching reading in first and subsequent languages, and devising intervention methods for reading disabilities.

2 487 000 €

Start date: 2012-05-01, End date: 2017-04-30

"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

A hallmark of cancer is tumor cell heterogeneity, which results from combinations of multiple genetic and epigenetic alterations within an individual tumor. In contrast, we have recently discovered that most human colorectal cancers (CRCs) are composed of mixtures of phenotypically distinct tumor cells organized into a stem cell hierarchy that displays a striking resemblance to the healthy colonic epithelium. We showed that long-term regeneration potential of tumor cells is largely influenced by the position that they occupy within the tumor's hierarchy. To analyze the organization of CRCs without the constraints imposed by tumor cell transplantation experiments, we have developed a method that allows for the first time tracking and manipulating the fate of specific cell populations in whole human tumors. This technology is based on editing the genomes of primary human CRCs cultured in the form of tumor organoids using Zinc-Finger Nucleases to knock-in either lineage tracing or cell ablation alleles in genes that define colorectal cancer stem cells (CRC-SCs) or differentiated-like tumor cells. Edited tumor organoids generate CRCs in mice that reproduce the tumor of origin while carrying the desired genetic modifications. This technological advance opens the gate to perform classical genetic and developmental analysis in human tumors. We will exploit this advantage to address fundamental questions about the cell heterogeneity and organization of human CRCs that cannot be tackled through currently existing experimental approaches such as: Are CRC-SCs the only tumor cell population with long term regenerating potential? Can we cure CRC with anti-CRC-SC specific therapies? Will tumor cell plasticity contribute to the regeneration of the CRC-SC pool after therapy? Do quiescent-SCs regenerate CRC tumors after standard chemotherapy? Can we identify these cells? How do common genetic alterations in CRC influence the CRC hierarchy? Do they affect the stem cell phenotype?

2 499 405 €

Start date: 2014-04-01, End date: 2019-03-31

Despite significant advance, cancer treatment remains suboptimal. Anatomical and physiological differences between humans and simple model organisms like Drosophila are many and major, and preclude the modelling of key aspects of the disease as it proceeds in vertebrates. However, malignant tumors in vertebrates and flies are made of cells that have derailed from their normal course of development, grow out of control, become immortal, invasive, and kill the host. Moreover, like most solid human tumors, Drosophila malignant tumors display chromosomal instability and copy number variation. In addition, some of them are characterized by the upregulation of germline genes, a distinct feature of certain human cancers. Drosophila tumor models offer an unprecedented opportunity to study these basic malignant traits, which characterize human tumors, in a genetically tractable organism, applying sophisticated genome-wide and comprehensive functional assays at a rate and with a level of detail that are not possible in vertebrates. The goal of this project is twofold: (1) to identify new paths of intervention to inhibit tumor growth, and (2) to determine the origin and function of aneuploidy and changes in gene copy number in malignant growth. We are expectant that the results obtained during the course of this project might eventually have a real impact in human health.

2 406 000 €

Start date: 2012-07-01, End date: 2017-06-30