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

Harmful traditions (e.g. child marriage, female genital cutting (FGC), breast ironing) affect millions of girls in developing countries. These customs have a strong detrimental effect on women’s human capital accumulation, empowerment and wellbeing, thus perpetuating gender imbalance and the vicious circle of poverty. Yet we know remarkably little on why these norms persist and what policies are able to eradicate them. This project will help to fill this gap. I will address the following research questions: How have harmful traditions originated in the first place and why do they persist over time? Given that simply legislating against harmful traditions is often ineffective, can we design policy interventions able to change them in a way that is conducive to development? To answer to the first question, I will start by investigating the historical roots of female genital cutting since slavery. Combining contemporary survey data with historical data on slave shipments by ethnic group and across slave routes, I will test whether current variation in FGC prevalence within Africa can be traced back to the Red Sea slave trades, where women were sold as concubines and infibulation was used to ensure chastity. I will then examine whether contemporaneous factors, and in particular current political institutions, play a role in perpetuating harmful norms, manipulating the timing of FGC to influence electoral outcomes. Finally, using climate data, I will provide new insights on the relationship between global warming and child marriage. To answer to the second question, I propose three randomized control trials uniquely designed to address specific determinants of the persistence of harmful traditions: alternative harmless rituals to remove cultural barriers, information provision to reduce breast ironing, peers’ interactions to decrease FGC and child marriage. Original data will be collected through field work, overcoming data limitations characterizing existing research.

1 389 688 €

Start date: 2020-05-01, End date: 2025-04-30

Nanomaterials are a promising technology that includes a variety of applications ranging from electronics to medicine. Within the family of nanomaterials, colloidal semiconductor nanocrystal (NCs) are among the most investigated, thanks to their desirable optoelectronic properties. Up until now, NCs have been employed in light-emitting diodes (LEDs) and lasers of relatively large size (devices of at least few hundred microns in area), therefore exploiting the properties of the ensemble (i.e., a NC film). LEDs based on ensemble of NCs show good performance in terms of efficiency and luminance but their applicability is still limited to standard consumer electronics products such as displays and illumination. Interestingly, thanks to quantum confinement a single isolated NC displays single photon emission, a desirable property for application in quantum technologies. Such property has been studied in detail using optical excitation. Yet, the challenge is to exploit single photon emission from a NC under electrical excitation but this requires the development of complex fabrication tools and methods for device preparation. NANOLED aims at developing light-emitting diodes based on individual colloidal NCs, thus paving the way to novel electrically driven single-photon sources with small footprint that are embeddable in photonic quantum networks. Further development of quantum technologies requires the investigation of devices based on novel materials for single photon generation. The project identifies 3 objectives to reach the final goal of fabricating a light-emitting diode based on a single nanocrystal: i) Identification and synthesis of semiconductor NCs with the necessary properties. ii) Development of methods for precise spatial positioning of a single semiconductor NC within electrodes able to inject a current into it; iii) Study of the electroluminescence of a single NC and investigation of its applicability toward single-photon and classical light sources.

1 496 250 €

Start date: 2020-01-01, End date: 2024-12-31

I propose here a research vision that aims to revolutionise the way we cure infections caused by intracellular pathogens, with the aim to find a universal therapy to infectious diseases that will also counteract the development of drug resistance. In PANDORA, I will specifically focus on eradicating human tuberculosis, one of the worst pandemics so far. To do this, I will first probe what are the molecular ‘bar-codes’ of infected cells, namely those specific membrane proteins that cells express upon infection. I will use this to reversely engineer a repertoire of super-selective polymeric nanoparticles - known as Polymersomes - that will carry ligands to recognise, bind, and selectively attack infected cells only, while leaving non-infected cells completely untouched. Such nanocarriers will access the infected cells and locally deliver their payload, which is the core technology of the therapy. Such technology will be inspired by what nature invented: I will reproduce the binding sequence of autolisins, proteins expressed by bacteriophages that specifically bind the wall of Mycobacteria species (the agent causing tuberculosis). I will thus create fusion antibodies (Ab) characterized by (i) the binding sequence of mycobacteriophages autolisins (for selective recognising intracellular Mycobacterial wall) and (ii) an effector region promoting bacterial clearance through either the macrophage-triggered phagocytosis or an ubiquitin-proteasome system. This therapy will represent a complete revolution in the field of new antimicrobial development, as it will combine complete bacterial eradication, development of memory immunity and fight against drug resistance, the three core pillars of this project. The super-selective polymersomes carrying the Abs-based universal therapy will be combined with the development of chimeric antigen receptor T-cells (CAR-T) against infection. These T-cells will be designed to chase and eradicate circulating infected cells in model organism.

1 495 018 €

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