ERC FUNDED PROJECTS

Neurons are morphologically complex cells that rely on highly compartmentalized signaling to coordinate cellular functions. The endocytic pathway is a crucial trafficking route by which neurons integrate, spatially process and transfer information. Endosomal trafficking in axons and dendrites ensures that required molecules and signaling complexes are present where and when they are functionally needed thus fulfilling essential roles in neuronal physiology. Our recent work has revealed the presence of mRNAs and ribosomes on endosomes in axons, raising the exciting possibility that these motile organelles also directly modulate the local proteome by controlling de novo protein synthesis. However, the mechanisms by which endosomes regulate mRNA translation in neurons is unknown. Moreover, the roles of endosome-mediated control of protein synthesis in neuronal development and function have not been investigated. Here, we propose to bridge this knowledge gap by elucidating links between the endocytic pathway and local protein synthesis in neurons, focusing on their functional relationship in axons. By combining genome-wide analysis, genetic tools, state-of-the-art imaging techniques and the use of Xenopus and mouse vertebrate models, we plan to address the following fundamental questions: (i) What are the mRNAs associated with endosomes and does endosomal trafficking regulate their axonal localization? (ii) Does the endocytic pathway mediate the selective translation of axonal mRNAs in response to extracellular factors? (iii) What are the endosome-associated RNA-binding proteins, and what is the effect of perturbing these associations on axonal development and maintenance in vivo? (iv) Does impaired endosomal regulation of axonal mRNA localization and translation cause axonopathies? Answering these questions will set strong foundations for this new area of research and can provide a new angle in our comprehension of neuropathies in need of novel therapeutic strategies.

1 499 563 €

Start date: 2020-09-01, End date: 2025-08-31

B3YOND proposes a radically new approach to nanofabrication, based on using sub-10 nm confined thermal reactions for patterning and manipulating the physical properties of materials with unprecedented tunability and resolution. Throughout the past decades, the progress in micro- and nano-fabrication techniques has been one of the most powerful and ubiquitous driving forces in science and technology. Nowadays, conventional approaches to nanofabrication reached the fundamental physical limits for the downscaling of devices, so that the search for groundbreaking new paradigms has become vital for enabling significant technological advancement. This project aims to go substantially beyond conventional nanofabrication approaches, through the following ambitious research objectives: 1) Demonstrate a radically new approach to nanofabrication, phase-nanoengineering, based on directly crafting at the nanoscale the physical properties of thin-film materials, by using the recently developed thermally assisted scanning probe lithography (t-SPL) technique for producing highly localized and tunable thermally-induced phase changes. 2) Develop a new class of artificial nanomaterials with unprecedented electronic transport properties, which arise from the proximity and coexistence of different structural and electronic phases, tailored at the nanoscale. 3) Realize novel monolithic three-dimensional nanoelectronic platforms for beyond-CMOS computing, by exploiting the unique capabilities of t-SPL for obtaining sub-10 nm resolution patterning in three-dimensions. By combining, in a highly multidisciplinary approach, some of the most promising recent advances in materials science, with the tremendous potential of t-SPL, this challenging project will enable disruptive conceptual and technological breakthroughs, beyond the conventional paradigms of nanofabrication.

1 498 385 €

Start date: 2021-02-01, End date: 2026-01-31

The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved. The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language. The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.

1 621 250 €

Start date: 2018-06-01, End date: 2023-05-31

This project is focused on the design, the production, the characterization, and the proposal for future commercialization of the first 1:1 scale 3D-printed realistic model of the brain tumor microenvironment with its associated blood neurovasculature. The proposed biomimetic dynamic 3D system, characterized by microcapillary diameter size and fluid flows similar to the in vivo physiological parameters, represents a drastic innovation with respect to other models well-established in the literature and available on the market, since it will allow to reliably reproduce the physiological environment and to accurately estimate the amount of drugs and/or of nanomaterial-associated compounds delivered through a modular length of the system. At the same time, in vitro 3D models are envisioned, allowing more physiologically-relevant information and predictive data to be obtained. All the artificial components will be fabricated through advanced lithography techniques based on two-photon polymerization (2pp), a disrupting mesoscale manufacturing approach which allows the fast fabrication of low-cost structures with nanometer resolution and great levels of reproducibility/accuracy. The proposed platform can be easily adopted in cell biology laboratories as multi-compartmental scaffold for the development of advanced co-culture systems, the primary biomedical applications of which consist in high-throughput screening of brain drugs and in testing of the efficacy of different anticancer therapies in vitro.

150 000 €

Start date: 2019-04-01, End date: 2020-09-30