ERC FUNDED PROJECTS

Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.

1 100 000 €

Start date: 2008-09-01, End date: 2014-04-30

The suite of graphene’s unique properties and applications can be enormously enhanced by its functionalization. As non-covalently functionalized graphenes do not target all graphene’s properties and may suffer from limited stability, covalent functionalization represents a promising way for controlling graphene’s properties. To date, only a few well-defined graphene derivatives have been introduced. Among them, fluorographene (FG) stands out as a prominent member because of its easy synthesis and high stability. Being a perfluorinated hydrocarbon, FG was believed to be as unreactive as the two-dimensional counterpart perfluoropolyethylene (Teflon®). However, our recent experiments showed that FG is not chemically inert and can be used as a viable precursor for synthesizing graphene derivatives. This surprising behavior indicates that common textbook grade knowledge cannot blindly be applied to the chemistry of 2D materials. Further, there might be specific rules behind the chemistry of 2D materials, forming a new chemical discipline we tentatively call 2D chemistry. The main aim of the project is to explore, identify and apply the rules of 2D chemistry starting from FG. Using the knowledge gained of 2D chemistry, we will attempt to control the chemistry of various 2D materials aimed at preparing stable graphene derivatives with designed properties, e.g., 1-3 eV band gap, fluorescent properties, sustainable magnetic ordering and dispersability in polar media. The new graphene derivatives will be applied in sensing, imaging, magnetic delivery and catalysis and new emerging applications arising from the synergistic phenomena are expected. We envisage that new applications will be opened up that benefit from the 2D scaffold and tailored properties of the synthesized derivatives. The derivatives will be used for the synthesis of 3D hybrid materials by covalent linking of the 2D sheets joined with other organic and inorganic molecules, nanomaterials or biomacromolecules.

1 831 103 €

Start date: 2016-06-01, End date: 2021-05-31

The goal of 2D-TOPSENSE is to exploit the remarkable stretchability of two-dimensional semiconductors to fabricate optoelectronic devices where strain is used as an external knob to tune their properties. While bulk semiconductors tend to break under strains larger than 1.5%, 2D semiconductors (such as MoS2) can withstand deformations of up to 10-20% before rupture. This large breaking strength promises a great potential of 2D semiconductors as ‘straintronic’ materials, whose properties can be adjusted by applying a deformation to their lattice. In fact, recent theoretical works predicted an interesting physical phenomenon: a tensile strain-induced semiconductor-to-metal transition in 2D semiconductors. By tensioning single-layer MoS2 from 0% up to 10%, its electronic band structure is expected to undergo a continuous transition from a wide direct band-gap of 1.8 eV to a metallic behavior. This unprecedented large strain-tunability will undoubtedly have a strong impact in a wide range of optoelectronic applications such as photodetectors whose cut-off wavelength is tuned by varying the applied strain or atomically thin light modulators. To date, experimental works on strain engineering have been mostly focused on fundamental studies, demonstrating part of the potential of 2D semiconductors in straintronics, but they have failed to exploit strain engineering to add extra functionalities to optoelectronic devices. In 2D-TOPSENSE I will go beyond the state of the art in straintronics by designing and fabricating optoelectronic devices whose properties and performance can be tuned by means of applying strain. 2D-TOPSENSE will focus on photodetectors with a tunable bandwidth and detectivity, light emitting devices whose emission wavelength can be adjusted, light modulators based on 2D semiconductors such as transition metal dichalcogenides or black phosphorus and solar funnels capable of directing the photogenerated charge carriers towards a specific position.

1 930 437 €

Start date: 2018-03-01, End date: 2023-02-28

I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.

2 311 696 €

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

This project aims to optimize and validate a promising therapeutic tool for combined cancer therapy, 2shRNA, in an ex vivo model system. Combined therapies are of great significance nowadays, due to their key role in fighting, for instances, resistance processes during cancer treatment. Nonetheless, the drug combinations approved to date face several problems, such as cooperative toxicity effects, lack of efficiency and poor bioavailability. We have designed and synthesized 2shRNA, a new bifunctional RNA tool that can simultaneously attack two therapeutic targets involved in drug resistance pathways, and that can additionally bind other molecules such as peptide carriers or fluorophores, to improve delivery and efficacy. The 2shRNA nanostructure displayed low toxicity and excellent anti-proliferative properties in resistant HER2+ breast cancer cell lines. The present proposal is aimed at optimizing and validating this novel and promising RNA tool by combining state-of-the-art bioinformatics design and cycles of chemical refinement with biological evaluation in PDx-derived primary cell cultures and biodistribution studies in PDx mouse models. The proposed strategy presents a novel therapeutic approach with great potential to circumvent drug resistance in breast cancer, which is a major health challenge for our society. The ability of our biostable RNA tool to administer two drugs in a single dose could improve the quality of life of the patients, as fewer doses might be needed to stall disease progression.

150 000 €

Start date: 2019-01-01, End date: 2020-06-30

Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques. The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas. The project consists of 3 research lines which follow a bottom-up approach: (1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics. (2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations. (3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona. Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.

1 512 250 €

Start date: 2019-05-01, End date: 2024-04-30

The classical view of genomes as linear sequences has been replaced by a vision of nuclear organization that is both dynamic and complex, with chromosomes and genes non-randomly positioned in the nucleus. Process compartmentalization and spatial location of genes modulate the transcriptional output of the genomes. However, how the interplay between genome structure and gene regulation is established and maintained is still unclear. The aim of this project is to explore whether the genome 3D structure acts as an information source for modulating transcription in response to external stimuli. With a genuine interdisciplinary team effort, we will study the conformation of the genome at various integrated levels, from the nucleosome fiber to the distribution of chromosomes territories in the nuclear space. We will generate high-resolution 3D models of the spatial organization of the genomes of distinct eukaryotic cell types in interphase to identify differences in the chromatin landscape. We will follow the time course of structural changes in response to cues that affect gene expression either permanently or transiently. We will analyze the changes in genome structure during the stable trans-differentiation of immortalized B cells to macrophages and during the transient hormonal responses of differentiated cells. We plan to establish novel functional strategies, based on targeted and high-throughput reporter assays, to assess the relevance of the spatial environment on gene regulation. Using sophisticated modeling and computational approaches, we will combine high-resolution data from chromosome interactions, super-resolution images and omics information. Our long-term plan is to implement a 3D browser for the comprehensive mapping of chromatin properties and genomic features, to better understand how external signals are integrated at the genomic, epigenetic and structural level to orchestrate changes in gene expression that are cell specific and dynamic.

12 272 645 €

Start date: 2014-06-01, End date: 2019-05-31

Optical bioimaging is limited by visible light penetration depth and stability of fluorescent dyes over extended periods of time. Surface enhanced Raman scattering (SERS) offers the possibility to overcome these drawbacks, through SERS-encoded nanoparticle tags, which can be excited with near-IR light (within the biological transparency window), providing high intensity, stable, multiplexed signals. SERS can also be used to monitor relevant bioanalytes within cells and tissues, during the development of diseases, such as tumours. In 4DBIOSERS we shall combine both capabilities of SERS, to go well beyond the current state of the art, by building three-dimensional scaffolds that support tissue (tumour) growth within a controlled environment, so that not only the fate of each (SERS-labelled) cell within the tumour can be monitored in real time (thus adding a fourth dimension to SERS bioimaging), but also recording the release of tumour metabolites and other indicators of cellular activity. Although 4DBIOSERS can be applied to a variety of diseases, we shall focus on cancer, melanoma and breast cancer in particular, as these are readily accessible by optical methods. We aim at acquiring a better understanding of tumour growth and dynamics, while avoiding animal experimentation. 3D printing will be used to generate hybrid scaffolds where tumour and healthy cells will be co-incubated to simulate a more realistic environment, thus going well beyond the potential of 2D cell cultures. Each cell type will be encoded with ultra-bright SERS tags, so that real-time monitoring can be achieved by confocal SERS microscopy. Tumour development will be correlated with simultaneous detection of various cancer biomarkers, during standard conditions and upon addition of selected drugs. The scope of 4DBIOSERS is multidisciplinary, as it involves the design of high-end nanocomposites, development of 3D cell culture models and optimization of emerging SERS tomography methods.

2 410 771 €

Start date: 2018-10-01, End date: 2023-09-30

It was early predicted by M. Green and coeval colleagues that dividing the solar spectrum into narrow ranges of colours is the most efficient manner to convert solar energy into electrical power. Multijunction solar cells are the current solution to this challenge, which have reached over 30% conversion efficiencies by stacking 3 junctions together. However, the large fabrication costs and time hinders their use in everyday life. It has been shown that highly mismatched alloy (HMA) materials provide a powerful playground to achieve at least 3 different colour absorption regions that enable optimised energy conversion with just one junction. Combining HMA-based junctions with standard Silicon solar cells will rocket solar conversion efficiency at a reduced price. To turn this ambition into marketable devices, several efforts are still needed and few challenges must be overcome. 4SUNS is a revolutionary approach for the development of HMA materials on Silicon technology, which will bring highly efficient multi-colour solar cells costs below current multijunction devices. The project will develop the technology of HMA materials on Silicon via material synthesis opening a new technology for the future. The understanding and optimization of highly mismatched alloy materials-using GaAsNP alloy- will provide building blocks for the fabrication of laboratory-size 4-colours/2-junctions solar cells. Using a molecular beam epitaxy system, 4SUNS will grow 4-colours/2-junctions structure as well as it will manufacture the final devices. Structural and optoelectronic characterizations will carry out to determine the quality of the materials and the solar cells characteristic to obtain a competitive product. These new solar cells are competitive products to breakthrough on the solar energy sector solar cells and allowing Europe to take leadership on high efficiency solar cells.

1 499 719 €

Start date: 2018-02-01, End date: 2023-01-31