ERC FUNDED PROJECTS

State-of-the-art microscopy and diffraction imaging provides insight into the atomic and sub-atomic structure of matter. They permit determination of the positions of atoms in a crystal lattice or in a molecule as well as the distribution of electrons inside atoms. State-of-the-art time-resolved spectroscopy with femtosecond and attosecond resolution provides access to dynamic changes in the atomic and electronic structure of matter. Our proposal aims at combining these two frontier techniques of XXI century science to make a long-standing dream of scientist come true: the direct observation of atoms and electrons in their natural state: in motion. Shifts in the atoms positions by tens to hundreds of picometers can make chemical bonds break apart or newly form, changing the structure and/or chemical composition of matter. Electronic motion on similar scales may result in the emission of light, or the initiation of processes that lead to a change in physical or chemical properties, or biological function. These motions happen within femtoseconds and attoseconds, respectively. To make them observable, we need a 4-dimensional (4D) imaging technique capable of recording freeze-frame snapshots of microscopic systems with picometer spatial resolution and femtosecond to attosecond exposure time. The motion can then be visualized by slow-motion replay of the freeze-frame shots. The goal of this project is to develop a 4D imaging technique that will ultimately offer picometer resolution is space and attosecond resolution in time.

2 500 000 €

Start date: 2010-03-01, End date: 2015-02-28

The sub-cellular processes that control the most critical aspects of life occur in three-dimensions (3D), and are intrinsically dynamic. While super-resolution microscopy has revolutionized cellular imaging in recent years, our current capability to observe the dynamics of life on the nanoscale is still extremely limited, due to inherent trade-offs between spatial, temporal and spectral resolution using existing approaches. We propose to develop and demonstrate an optical microscopy methodology that would enable live sub-cellular observation in unprecedented detail. Making use of multicolor 3D point-spread-function (PSF) engineering, a technique I have recently developed, we will be able to simultaneously track multiple markers inside live cells, at high speed and in five-dimensions (3D, time, and color). Multicolor 3D PSF engineering holds the potential of being a uniquely powerful method for 5D tracking. However, it is not yet applicable to live-cell imaging, due to significant bottlenecks in optical engineering and signal processing, which we plan to overcome in this project. Importantly, we will also demonstrate the efficacy of our method using a challenging biological application: real-time visualization of chromatin dynamics - the spatiotemporal organization of DNA. This is a highly suitable problem due to its fundamental importance, its role in a variety of cellular processes, and the lack of appropriate tools for studying it. The project is divided into 3 aims: 1. Technology development: diffractive-element design for multicolor 3D PSFs. 2. System design: volumetric tracking of dense emitters. 3. Live-cell measurements: chromatin dynamics. Looking ahead, here we create the imaging tools that pave the way towards the holy grail of chromatin visualization: dynamic observation of the 3D positions of the ~3 billion DNA base-pairs in a live human cell. Beyond that, our results will be applicable to numerous 3D micro/nanoscale tracking applications.

1 802 500 €

Start date: 2018-11-01, End date: 2023-10-31

When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.

1 969 750 €

Start date: 2019-02-01, End date: 2024-01-31

The proposed work concerns the theoretical and numerical development of robust and adaptive methodologies for broadband imaging in clutter. The word clutter expresses our uncertainty on the wave speed of the propagation medium. Our results are expected to have a strong impact in a wide range of applications, including underwater acoustics, exploration geophysics and ultrasound non-destructive testing. Our machinery is coherent interferometry (CINT), a state-of-the-art statistically stable imaging methodology, highly suitable for the development of imaging methods in clutter. We aim to extend CINT along two complementary directions: novel types of applications, and further mathematical and numerical development so as to assess and extend its range of applicability. CINT is designed for imaging with partially coherent array data recorded in richly scattering media. It uses statistical smoothing techniques to obtain results that are independent of the clutter realization. Quantifying the amount of smoothing needed is difficult, especially when there is no a priori knowledge about the propagation medium. We intend to address this question by coupling the imaging process with the estimation of the medium's large scale features. Our algorithms rely on the residual coherence in the data. When the coherent signal is too weak, the CINT results are unsatisfactory. We propose two ways for enhancing the resolution of CINT: filter the data prior to imaging (noise reduction) and waveform design (optimize the source distribution). Finally, we propose to extend the applicability of our imaging-in-clutter methodologies by investigating the possibility of utilizing ambient noise sources to perform passive sensor imaging, as well as by studying the imaging problem in random waveguides.

690 000 €

Start date: 2010-06-01, End date: 2015-11-30