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

My research encompasses the application of novel methods and strategies in the field of low energy particle physics. The goal of the presented program is to lead an independent and highly competitive experiment to search for a CP violating neutron electric dipole moment (nEDM), as well as for new exotic interactions using highly sensitive neutron and proton spin resonance techniques. The measurement of the nEDM is considered to be one of the most important fundamental physics experiments at low energy. It represents a promising route for finding new physics beyond the standard model (SM) and describes an important search for new sources of CP violation in order to understand the observed large baryon asymmetry in our universe. The main project will follow a novel concept based on my original idea, which plans to employ a pulsed neutron beam at high intensity instead of the established use of storable ultracold neutrons. This complementary and potentially ground-breaking method provides the possibility to distinguish between the signal due to a nEDM and previously limiting systematic effects, and should lead to an improved result compared to the present best nEDM beam experiment. The findings of these investigations will be of paramount importance and will form the cornerstone for the success of the full-scale experiment intended for the European Spallation Source. A second scientific question will be addressed by performing spin precession experiments searching for exotic short-range interactions and associated light bosons. This is a vivid field of research motivated by various extensions to the SM. The goal of these measurements, using neutrons and protons, is to search for additional interactions such new bosons mediate between ordinary particles. Both topics describe ambitious and unique efforts. They use related techniques, address important questions in fundamental physics, and have the potential of substantial scientific implications and high-impact results.

1 404 062 €

Start date: 2017-04-01, End date: 2022-03-31

The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (“multitasking cell types”), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform “a single computation” or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.

1 499 000 €

Start date: 2010-11-01, End date: 2015-10-31

Nanoscale systems binding single molecules, or small numbers of molecules, in conducting junctions show considerable promise for a range of technological applications, from photovoltaics to rectifiers to sensors. These environments differ significantly from the traditional domain of chemical studies involving molecules in solution and the gas phase, necessitating renewed efforts to understand the physical properties of these systems. The objective of this proposal concerns one particular class of physical processes: understanding and controlling local heating in molecular junctions in terms of excitation, dissipation and transfer. Local heating and dissipation in molecular junctions has long been a concern due to the possibly detrimental impact on device stability and function. More recently there has been increased interest, as these processes underlie both spectroscopic techniques and potential technological applications. Together these issues make an investigation of ways to chemically control local heating in molecular junctions timely and important. The proposal objective will be addressed through the investigation of three challenges: - Developing chemical control of local heating in molecular junctions. - Developing chemical control of heat dissipation in molecular junctions. - Design of optimal thermoelectric materials. These three challenges constitute distinct, yet complementary, avenues for investigation with progress in each area supporting the other two. All three challenges build on existing theoretical methods, with the important shift of focus to methods to achieve chemical control. The combination of state-of-the-art computational methods with careful chemical studies promises significant new developments for the area.

1 499 999 €

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