ERC FUNDED PROJECTS

The centriole is the largest evolutionary conserved macromolecular structure responsible for building centrosomes and cilia or flagella in many eukaryotes. Centrioles are critical for the proper execution of important biological processes ranging from cell division to cell signaling. Moreover, centriolar defects have been associated to several human pathologies including ciliopathies and cancer. This state of facts emphasizes the importance of understanding centriole biogenesis. The study of centriole formation is a deep-rooted question, however our current knowledge on its molecular organization at high resolution remains fragmented and limited. In particular, exquisite details of the overall molecular architecture of the human centriole and in particular of its central core region are lacking to understand the basis of centriole organization and function. Resolving this important question represents a challenge that needs to be undertaken and will undoubtedly lead to groundbreaking advances. Another important question to tackle next is to develop innovative methods to enable the nanometric molecular mapping of centriolar proteins within distinct architectural elements of the centriole. This missing information will be key to unravel the molecular mechanisms behind centriolar organization. This research proposal aims at building a cartography of the human centriole by elucidating its molecular composition and architecture. To this end, we will combine the use of innovative and multidisciplinary techniques encompassing spatial proteomics, cryo-electron tomography, state-of-the-art microscopy and in vitro assays and to achieve a comprehensive molecular and structural view of the human centriole. All together, we expect that these advances will help understand basic principles underlying centriole and cilia formation as well as might have further relevance for human health.

1 498 965 €

Start date: 2017-01-01, End date: 2021-12-31

Interferometers are fundamental tools for the study of nature laws and for the precise measurement and control of the physical world. In the last century, the scientific and technological progress has proceeded in parallel with a constant improvement of interferometric performances. For this reason, the challenge of conceiving and realizing new generations of interferometers with broader ranges of operation and with higher sensitivities is always open and actual. Despite the introduction of laser devices has deeply improved the way of developing and performing interferometric measurements with light, the atomic matter wave analogous, i.e. the Bose-Einstein condensate (BEC), has not yet triggered any revolution in precision interferometry. However, thanks to recent improvements on the control of the quantum properties of ultra-cold atomic gases, and new original ideas on the creation and manipulation of quantum entangled particles, the field of atom interferometry is now mature to experience a big step forward. The system I want to realize is a Mach-Zehnder spatial interferometer operating with trapped BECs. Undesired decoherence sources will be suppressed by implementing BECs with tunable interactions in ultra-stable optical potentials. Entangled states will be used to improve the sensitivity of the sensor beyond the standard quantum limit to ideally reach the ultimate, Heisenberg, limit set by quantum mechanics. The resulting apparatus will show unprecedented spatial resolution and will overcome state-of-the-art interferometers with cold (non condensed) atomic gases. A successful completion of this project will lead to a new generation of interferometers for the immediate application to local inertial measurements with unprecedented resolution. In addition, we expect to develop experimental capabilities which might find application well beyond quantum interferometry and crucially contribute to the broader emerging field of quantum-enhanced technologies.

1 068 000 €

Start date: 2011-01-01, End date: 2015-12-31

In quantum electrodynamics a range of fundamental processes are driven by omnipresent vacuum fluctuations. Photonic crystals can control vacuum fluctuations and thereby the fundamental interaction between light and matter. We will conduct experiments on quantum dots in photonic crystals and observe novel quantum electrodynamics effects including fractional decay and the modified Lamb shift. Furthermore, photonic crystals will be explored for shielding sensitive quantum-superposition states against decoherence. Defects in photonic crystals allow novel functionalities enabling nanocavities and waveguides. We will use the tight confinement of light in a nanocavity to entangle a quantum dot and a photon, and explore the scalability. Controlled ways of generating scalable and robust quantum entanglement is the essential missing link limiting quantum communication and quantum computing. A single quantum dot coupled to a slowly propagating mode in a photonic crystal waveguide will be used to induce large nonlinearities at the few-photon level. Finally we will explore a novel route to enhanced light-matter interaction employing controlled disorder in photonic crystals. In disordered media multiple scattering of light takes place and can lead to the formation of Anderson-localized modes. We will explore cavity quantum electrodynamics in Anderson-localized random cavities considering disorder a resource and not a nuisance, which is the traditional view. The main focus of the project will be on optical experiments, but fabrication of photonic crystals and detailed theory will be carried out as well. Several of the proposed experiments will constitute milestones in quantum optics and may pave the way for all-solid-state quantum communication with quantum dots in photonic crystals.

1 199 648 €

Start date: 2010-12-01, End date: 2015-11-30

DNA repair pathways evolved as an intricate network that senses DNA damage and resolves it in order to minimise genetic lesions and thus preventing tumour formation. Gaining in recognition the last few years, the alternative end-joining (alt-EJ) DNA repair pathway was recently shown to be up-regulated and required for cancer cell viability in the absence of homologous recombination-mediated repair (HR). Despite this integral role, the alt-EJ repair pathway remains poorly characterised in humans. As such, its molecular composition, regulation and crosstalk with HR and other repair pathways remain elusive. Additionally, the contribution of the alt-EJ pathway to tumour progression as well as the identification of a mutational signature associated with the use of alt-EJ has not yet been investigated. Moreover, the clinical relevance of developing small-molecule inhibitors targeting players in the alt-EJ pathway, such as the polymerase Pol Theta (Polθ), is of importance as current anticancer drug treatments have shown limited effectiveness in achieving cancer remission in patients with HR-deficient (HRD) tumours. Here, we propose a novel, multidisciplinary approach that aims to characterise the players and mechanisms of action involved in the utilisation of alt-EJ in cancer. This understanding will better elucidate the changing interplay between different DNA repair pathways, thus shedding light on whether and how the use of alt-EJ contributes to the pathogenic history and survival of HRD tumours, eventually paving the way for the development of novel anticancer therapeutics. For all the abovementioned reasons, we are convinced this project will have important implications in: 1) elucidating critical interconnections between DNA repair pathways, 2) improving the basic understanding of the composition, regulation and function of the alt-EJ pathway, and 3) facilitating the development of new synthetic lethality-based chemotherapeutics for the treatment of HRD tumours.

1 498 750 €

Start date: 2017-07-01, End date: 2022-06-30