ERC FUNDED PROJECTS

Colloidal semiconductor nanocrystals have already found significant use in various arenas, including bioimaging, displays, lighting, photovoltaics and catalysis. Here we aim to harness the extremely broad synthetic toolbox of colloidal semiconductor quantum dots in order to utilize them as unique sources of quantum states of light, extending well beyond the present attempts to use them as single photon sources. By tailoring the shape, size, composition and the organic ligand layer of quantum dots, rods and platelets, we propose their use as sources exhibiting a deterministic number of emitted photons upon saturated excitation and as tunable sources of correlated and entangled photon pairs. The versatility afforded in their fabrication by colloidal synthesis, rather than by epitaxial growth, presents a potential pathway to overcome some of the significant limitations of present-day solid state sources of nonclassical light, including color tunability, fidelity and ease of assembly into devices. This program is a concerted effort both on colloidal synthesis of complex multicomponent semiconductor nanocrystals and on cutting edge photophysical studies at the single nanocrystal level. This should enable new types of emitters of nonclassical light, as well as provide a platform for the implementation of recently suggested schemes in quantum optics which have never been experimentally demonstrated. These include room temperature sources of exactly two (or more) photons, correlated photon pairs from quantum dot molecules and entanglement based on time reordering. Fulfilling the optical and material requirements from this type of system, including photostability, control of carrier-carrier interactions, and a large quantum yield, will inevitably reveal some of the fundamental properties of coupled carriers in strongly confined structures.

2 000 000 €

Start date: 2016-05-01, End date: 2021-04-30

The interaction and communication between individual cells plays a central role in virtually all fields of biology, from the cooperative work of cells in the immune system, through the differentiation of stem cells, and to the proliferation of cancer cells. In recent years it has been shown that these processes are fundamentally coupled to cell-to-cell heterogeneity and variability. Despite the fact that studying cellular ensembles obscures these fundamental biological processes, most current studies consider cell populations, largely due to technological limitations in the ability to dynamically compartmentalize, manipulate, and analyze single cells. We propose to develop and demonstrate a new concept for a single-cell-level bioanalytical workspace that is dynamically configurable in real time. Making use of electrokinetically driven surface deformations, a physical mechanism recently invented in my lab, the MetamorphChip will be able to dynamically modify its own microfluidic structure, thus allowing complete freedom in the manipulation of individual cells and their environment, in real time. The project is divided into 5 aims: 1. Deepening our physical understanding of electrokinetically driven surface deformations, and using it to create a “library” of fundamental dynamic elements. 2. Designing, building, and testing the first prototype MetamorphChip. 3. Demonstrating the ability of the MetamorphChip to manipulate single cells and their microenvironment. 4. Performing advanced biochemical analysis on single cells using the chip. 5. Demonstrating the use of the MetamorphChip for experimental study of immune cell interaction. I strongly believe that successful implementation of this project would fundamentally change the way in which single-cell experiments are conceived and performed.

1 744 056 €

Start date: 2016-04-01, End date: 2021-03-31

The aim of my project is to establish a multidisciplinary platform for quantitative biophysical analysis of protein-protein interactions in health and disease as a basis for drug design: (1) Analyzing protein-protein interactions at the molecular level in healthy systems; (2) Understanding what goes wrong in disease at the molecular level; (3) Development of drugs that will restore the biological system to its healthy conditions. My team will apply this approach to establish the concept of shifting the oligomerization equilibrium of proteins as a therapeutic strategy. I will expand the concepts of allosteric inhibitors and chemical chaperones, and develop the “shiftides”: peptides that shift the oligomerization equilibrium of a protein to modulate its activity, as a new and widely applicable methodology for drug design. I will apply this concept for: (1) inhibiting a protein by binding preferentially to the inactive oligomeric state and shifting the oligomerization equilibrium of the protein towards it; I have demonstrated the feasibility of this approach and developed promising anti-HIV peptides that inhibit the HIV-1 integrase and consequently HIV-1 replication in cells by shifting the integrase oligomerization equilibrium from the active dimer to the inactive tetramer. My team will further develop these peptides, and apply the same approach to inhibit the HIV proteins reverse transcriptase and protease; (2) Activating a protein by binding preferentially to the active oligomeric state and shifting the oligomerization equilibrium towards it: This will be applied for activation of the tumor suppressor p53, by shifting its oligomerization equilibrium from the inactive dimer to the active tetramer. Such shiftides will serve as anti-cancer lead compounds. My project will open new doors in the field of drug design, and at the end of the five-year period will result in a general new methodology to affect protein function for medical purposes.

1 250 000 €

Start date: 2008-07-01, End date: 2013-06-30

"We propose to develop and implement advanced magnetic resonance detection and micro-imaging techniques that will benefit many biophysical, chemical, physical, and medical applications. Magnetic resonance (MR) is one of the most profound observation methods in science. MR includes Nuclear Magnetic Resonance (NMR) and Electron Spin Resonance (ESR). It has a variety of applications ranging from chemical structure determination to medical imaging and quantum computing. From a scientific standpoint, MR was the main focus of at least seven Nobel prizes in physics, chemistry, and medicine. From an industrial standpoint, MR is a multibillion industry focused on a range of medical (MRI) and chemical applications (MR spectrometers). Despite the fact that magnetic resonance was discovered more than 60 years ago, there is still plenty of room for new methodologies and applications. This research will confront some of the most challenging issues that this field has yet to offer, which also contain the greatest potential benefits. This is what we call “The MR Challenge”. We will focus on three key MR issues: sensitivity, image resolution, and affordability. Our first goal is to substantially improve the sensitivity of MR spectroscopy and the resolution of MR micro-imaging. We will put most of our efforts on ESR spectroscopy and on the detection of NMR information through an ESR signal (ENDOR). At ambient conditions our goal is to achieve a sensitivity of ~10^4 electron spins and a resolution of 1 micron; at low temperatures we will approach single electron spin sensitivity and image resolution as high as 10nm. In terms of affordability, our goal is to introduce a small probe that is capable of acquiring NMR spectra from samples located outside the magnet (an ""ex-situ"" probe). We will also design and construct a new family of hand-held 3D NMR imaging probes. The new capabilities would be applied in the field of single cell imaging and biophysics, materials science, and medicine."

1 250 000 €

Start date: 2008-08-01, End date: 2013-07-31