ERC Awardees

​​​The Nanocenter of the Hebrew University promotes excellence in nanoscience research. This is well reflected in the exceptional success in awarding of the highly competitive and prestigious ERC grants to the Nanocenter members. So far 27 grants were awarded: 3 advanced grants, 4 consolidators and 20 starting grants.

Dr. Yonathan Anahory The Racah Institute of Physics,

​​​​Starting Grant (2018)
Project:Nanoscale magnetic and thermal imaging of strongly correlated electronic materials

Prof. Uri Banin Institute of Chemistry, Faculty of Science

​​Advanced Grant (2009)
Project: Doping, Charge Transfer and Energy Flow in Hybrid Nanoparticle Systems.
Advanced Grant (2016)
Project:Coupled Nanocrystal Molecules: Quantum coupling effects via chemical coupling of colloidal nanocrystals​

​​Summary (2009): We target a frontier in nanocrystalS science of combining disparate materials into a single hybrid nanosystem. This offers an intriguing route to engineer nanomaterials with multiple functionalities in ways that are not accessible in bulk materials or in molecules. Such control of novel material combinations on a single nanoparticle or in a super-structure of assembled nanoparticles, presents alongside with the synthesis challenges, fundamental questions concerning the physical attributes of nanoscale systems. My goals are to create new highly controlled hybrid nanoparticle systems, focusing on combinations of semiconductors and metals, and to decipher the fundamental principles governing doping in nanoparticles and charge and energy transfer processes among components of the hybrid systems. The research addresses several key challenges: First, in synthesis, combining disparate material components into one hybrid nanoparticle system. Second, in self assembly, organizing a combination of semiconductor (SC) and metal nanoparticle building blocks into hybrid systems with controlled architecture. Third in fundamental physico-chemical questions pertaining to the unique attributes of the hybrid systems, constituting a key component of the research. A first aspect concerns doping of SC nanoparticles with metal atoms. A second aspect concerns light-induced charge transfer between the SC part and metal parts of the hybrid constructs. A third related aspect concerns energy transfer processes between the SC and metal components and the interplay between near-field enhancement and fluorescence quenching effects. Due to the new properties, significant impact on nanocrystal applications in solar energy harvesting, biological tagging, sensing, optics and electropotics is expected.​

Prof. Nir Bar-Gill Department of Applied Physics and Institute of Physics, Faculty of Science

​​​​​​​Starting Grant (2016)
Project: Quantum spin simulators in diamond

Summary: Quantum interacting systems are at the forefront of contemporary physics, and pose challenges to our understanding of quantum phases, many-body dynamics, and a variety of condensed matter phenomena. Advances in quantum applications, including quantum computation and metrology, rely on interactions to create entanglement and to improve sensitivity beyond the standard quantum limit. In recent years tremendous effort has been invested in developing precision experimental tools to study and simulate complicated many-body Hamiltonians. So far, such tools have been mostly realized in cold atomic systems, trapped ions and photonic networks.

I propose a novel experimental approach using Nitrogen-Vacancy (NV) color centers in diamond, superconducting couplers, super-resolution addressing and cryogenic cooling, as a many-body quantum spin simulator. The NV center is a unique spin defect in a robust solid, with remarkable optical properties and a long electronic spin coherence lifetime (∼3 ms at room temperature). We have recently demonstrated that this coherence time can be extended to almost 1 second at low temperature, paving the way for interaction-dominated NV-based experiments.

The goal of this project is to develop a paradigm of atom-like spin defects in the solid-state as a platform for studying elaborate quantum many-body spin physics (e.g. the Haldane phase in 2D) and quantum information systems (e.g. one-way quantum computing). I intend to combine a low temperature environment with a novel optical super-resolution system and nanofabricated superconducting structures on the diamond surface to produce a unique experimental setup capable of achieving this goal. The ability to engineer and control interacting NV systems in the solid-state diamond lattice has far-reaching applications for studying fundamental problems in many-body physics and in quantum information science.

Prof. Yechezkel Barenholz Department of Biochemistry and Molecular Biology, , Faculty of Medicine

Team Member​​ (2009)
Hydration lubrication: exploring a new

​​Summary: In recent years, as first established in some 6 papers in Science and Nature from the PI s group, a new paradigm has emerged. This reveals the remarkable and unsuspected - role of hydration layers in modulating frictional forces between sliding surfaces or molecular layers in aqueous media, termed hydration lubrication, in which the lubricating mode is completely different from the classic one of oils or surfactants. In this project we address the substantial challenges that have now arisen: what are the underlying mechanisms controlling this effect? what are the potential breakthroughs that it may lead to? We will answer these questions through several interrelated objectives designed to address both fundamental aspects, as well as limits of applicability. We will use surface force balance (SFB) experiments, for which we will develop new methodologies, to characterize normal and frictional forces between atomically smooth surfaces where the nature of the surfaces (hydrophilic, hydrophobic, metallic, polymeric), as well as their electric potential, may be independently varied. We will examine mono- and multivalent ions to establish the role of relaxation rates and hydration energies in controlling the hydration lubrication, will probe hydration interactions at both hydrophobic/hydrophilic surfaces and will monitor slip of hydrated ions past surfaces. We will also characterize the hydration lubrication properties of a wide range of novel surface systems, including surfactants, liposomes, polymer brushes and, importantly, liposomes, using also synchrotron X-ray reflectometry for structural information. Attainment of these objectives should lead to conceptual breakthroughs both in our understanding of this new paradigm, and for its practical implications.

Dr. Ofra Benny School of Pharmacy - Institute of Drug Research, Faculty of Medicine

​​​​​​​​​Starting Grant (2017)
Project:Mechanical Targeting as an Integrative Approach for Personalized Nanomedicine.

Dr. Galia Blum School of Pharmacy - Institute for Drug Research,, Faculty of Medicine

​​Starting Grant (2013)
Project: Protease Activated X-Ray Contrast Agents for Molecular Imaging of Vulnerable Atherosclerotic Plaques and Cancer Development using Spectral CT

Summary: The major causes of death in the Western world are cardiovascular diseases and cancer. More accurate detection of these diseases will improve clinical outcomes. Thus, we will develop unique X-ray contrast reagents for use in spectral computerized tomography (CT) that bind active proteases to reveal the exact location and stage of cancer and atherosclerosis. Activity-based probes (ABPs) are small molecules that covalently bind to active proteases. Based on our success in developing optical ABPs for non-invasive optical detection of cancer and atherosclerosis, we will focus on two novel types of reagents: (1) ABPs conjugated to the various contrast elements that can be visualized by x-rays. (2) “smart probes” conjugated to different contrast reagents on each side of the molecule to overcome clearance limitations. Protease found in diseased tissue will selectively bind and remove a part of the molecule, changing the physical properties of the bound probe. Thus, different signals from bound and unbound probes could be detected by photon counting spectral CT scanners. Our initial target, cysteine cathepsin proteases, are overexpressed and activated in cancer and arthrosclerosis. The level of active cathepsins correlates with progression of both diseases, thereby serving as a promising biomarker for these pathologies. The “smart probes” are an innovative type of spectral CT agent that will enable high-resolution rapid imaging in humans before probe clearance. Our probes increase imaging sensitivity since the contrast element remains at the desired site. Moreover, the levels of active cathepsins will reveal critical information regarding disease progression, yielding more accurate diagnoses and improved personalized treatment. For example, these reagents can distinguish between a vulnerable and stable atherosclerotic plaque. Thus, our novel probes will directly reduce cancer and cardiovascular disease mortality by enabling earlier and more accurate disease detection.​

Prof. Ido Braslavsky Institute of Biochemistry Food Science and Nutrition, Faculty of Agriculture

Starting Grant (2011)
Project: Improved Cryopreservation using Ice Binding Proteins.

​​Summary:Several organisms have evolved specialized ice binding proteins (IBPs) that prevent their body fluids from freezing (antifreeze proteins, AFPs), inhibit recrystallization of ice in frozen tissues, or initiate freezing at moderate supercooling temperatures (ice nucleating proteins, INPs). These proteins have many potential applications in agriculture, food preservation, cryobiology, and biomedical science. The ubiquitous presence of IBPs in such organisms indicates the power of these molecules to enable survival under cold conditions. Despite this key role in nature, however, IBPs have been effectively exploited in only one cryopreservation application, namely, recrystallization inhibition in ice cream. Several terrestrial organisms, including insects, have developed very active forms of AFPs. These hyperactive AFPs (hypAFPs) have not been utilized significantly thus far in cryopreservation techniques. The gap between the obvious potential of IBPs and their actual applications stems from a lack of knowledge regarding the mechanisms by which IBPs interact with ice surfaces and how these proteins can assist in cryoprotection. I propose to investigate the mechanism by which IBPs inhibit ice crystallization and the use of such proteins for cryopreserving cells, tissues, and organisms. My group has a strong record in the study of the interactions between IBPs and ice using novel methods that we have developed, including fluorescence microscopy techniques combined with cooled microfluidic devices. We will investigate the interactions of AFPs with ice and the use of hypAFPs in cryopreservation procedures. This research will contribute to an understanding of the mechanisms by which IBPs act, and apply the acquired knowledge to cryopreservation. The successful implementation of IBPs in cryopreservation would revolutionize the field of cryobiology, with enormous implications for cryopreservation applications in general and the frozen and chilled food industry in particular.

Dr. Amnon Buxboim Institute of Life Sciences and School of Engineering, Faculty of Science

​​​​​​​​Starting Grant (2015)
Project: Mechanobiology of Bovine Reproduction​

​​​​Summary:The global demand for dairy products is expected to surge by 36% over the next decade in a manner that is progressively insatiable by existing technologies. The dairy industry relies on bovine reproduction, yet cow fertility is declining and the exact causes are not fully understood. It is clear, however, that the quality of bovine oocytes is decreasing.

In mammals, the ovarian reserve of oocytes stored within quiescent primordial follicles is non-renewable. Oocyte develop and mature within distinctive follicular microenvironments under tightly regulated molecular and physical conditions. Similarly, preimplantation embryo development is supported within a specialized microenvironment that is surrounded by the zona pellucida and insulated from external soluble and mechanical inputs. Characterizing and understanding these environments and how they affect reproductive processes is a key toward improving assisted reproductive technologies in bovine species.

Our premise is that molecular characterization of endocrine and paracrine signalling pathways must be complemented with understanding the mechanical regulation of reproductive biology. This premise is supported by recent finding showing that physical stresses and the mechanical compliance of the extracellular surroundings serve as potent regulators of cell fates in regeneration processes, development, and disease.

I propose to employ a biophysical and computational toolbox to study the mechanobiology of reproduction with application to bovine embryo-based technologies. By mimicking the mechanical properties of the ovarian cortical niche, which I will characterize using freshly derived ovaries, I will design an in vitro system for supporting follicle growth. Mechanical profiling of the entire developmental course from oocyte maturation to preimplantation embryogenesis will generate mechanistic insights into the physical regulation of reproductive processes.

Prof. Assaf Friedler Institute of Chemistry, Faculty of Science

​​Starting Grant (2011)
Project: Algal Bloom Dynamics: From Cellular Mechanisms to Trophic Level Interactions

​​Summary: 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.

Dr. Elad Gross Institute of Chemistry, Faculty of Science

​​Starting Grant (2018)
Project:High spatial resolution mapping of catalytic reactions
on single nanoparticles
High spatial resolution mapping of catalytic reactions
on single nanoparticles

Summary:Catalytic nanoparticles are heterogeneous in their nature - and even within the simplest particles structural
and compositional differences exist and affect the overall performances of a catalyst. Thus non-disruptive,
detailed chemical information at the nanoscale is essential for understanding how surface properties direct
the reactivity of these particles. Infrared spectroscopy offers a low-energy route towards conducting in-situ,
high spatial resolution mapping of catalytic reactions on the surface of single nanoparticles, yielding the
influence of various physiochemical properties on the catalytic reactivity.
In the project my team will employ recently developed Infrared nanospectroscopy measurements to provide
high spatial resolution mapping of catalytic reactions on the surface of metallic nanoparticles, while using
chemically active N-heterocyclic carbene molecules as indicators for surface reactivity. With this setup I will
address fundamental questions in catalysis research and identify, on a single particle basis and under reaction
conditions, the ways by which the size, structure, composition and metal-support interactions direct the
reactivity of metallic nanoparticles in hydrogenation, oxidation and functionalization reactions. My research
group demonstrated recently the feasibility of this novel approach by which structure-reactivity correlations
were identified within single nanoparticles. Knowledge gained in this project will provide in-depth
understanding of the basic elements that control the reactivity of heterogeneous catalysts and enable the
development of optimized catalysts based on rational design. Moreover, one can foresee wide application
potential for this experimental approach in various other research fields like batteries and fuel cells, in which
high spatial resolution analysis of reactive surfaces is essential for understanding structure-reactivity

Prof. Nadav Katz Institute of Physics, Faculty of Science

Starting Grant (2013)
Project: Quantum walks in superconducting networks

​​​​​Summary: "I propose to build a general purpose continuous quantum walk platform using superconducting devices (resonators, qubits and SQUIDS). This system will include up to 40 sites and will implement basic quantum simulation algorithms, generalized interferometry and explore the quantum-classical boundary for many-particle entangled systems. Quantum walks (QW) are a novel scheme for quantum information processing. The core idea is to encode the problem into a network and propagate quantum particles within. The entanglement of the many-body state due to interference between sites of the network brings, at the appropriate time, to a desired answer/observable. Recent implementations with optical photons or trapped ions and atoms have brought this theoretical process to the forefront of fundamental and applied quantum engineering. In parallel, superconducting devices are experiencing a renaissance due to modern understanding of materials, fundamental physics of superconductivity and fabrication techniques. The coherence times of superconducting qubits have improved by almost 5 (!) orders of magnitude over the past ten years. Recent developments include single microwave sources and detectors, quantum-limited amplifiers, heterodyne techniques for measurement and state tomography. Building such a network involves significant challenges, both fundamental and technical. On the fundamental level I intend to improve coherence times of our devices by advanced material science characterization, simulation tools and rapid turn-around characterization. My group will build a ""quantum compiler"" system for designing new layouts, bridging abstract design to implementation. On the technical level we will implement a flip chip bias circuit to overcome site inhomogeneity and for evolving and measuring results. This will be an enabling system for a broad range of quantum information processing applications and fundamental experiments, with unprecedented computational power and flexibility."

Dr. Ori Katz Dept. of Applied Physics, School of Computer Science & Engineering

Starting Grant (2015)
Project: Deep non-invasive imaging via scattered-light acoustically-mediated computational microscopy


Summary:Optical microscopy, perhaps the most important tool in biomedical investigation and clinical diagnostics, is currently held back by the assumption that it is not possible to noninvasively image microscopic structures more than a fraction of a millimeter deep inside tissue. The governing paradigm is that high-resolution information carried by light is lost due to random scattering in complex samples such as tissue. While non-optical imaging techniques, employing non-ionizing radiation such as ultrasound, allow deeper investigations, they possess drastically inferior resolution and do not permit microscopic studies of cellular structures, crucial for accurate diagnosis of cancer and other diseases.
I propose a new kind of microscope, one that can peer deep inside visually opaque samples, combining the sub-micron resolution of light with the penetration depth of ultrasound. My novel approach is based on our discovery that information on microscopic structures is contained in random scattered-light patterns. It breaks current limits by exploiting the randomness of scattered light rather than struggling to fight it.
We will transform this concept into a breakthrough imaging platform by combining ultrasonic probing and modulation of light with advanced digital signal processing algorithms, extracting the hidden microscopic structure by two complementary approaches: 1) By exploiting the stochastic dynamics of scattered light using methods developed to surpass the diffraction limit in optical nanoscopy and for compressive sampling, harnessing nonlinear effects. 2) Through the analysis of intrinsic correlations in scattered light that persist deep inside scattering tissue.
This proposal is formed by bringing together novel insights on the physics of light in complex media, advanced microscopy techniques, and ultrasound-mediated imaging. It is made possible by the new ability to digitally process vast amounts of scattering data, and has the potential to impact many fields.​

Prof. Uriel Levy Department of Applied Physics, School of Computer Science & Engineering

Consolidators grants (2014)
Project: Light-Vapour Interactions at the Nanoscale​

​​Summary: The goal of this research is to develop a chip scale toolkit for exploring light-vapour interactions at the nanoscale. The integration of hot vapour cells with nanophotonics technology will be used for enhancing the interaction of light with vapours and for constructing miniaturized devices. Our main objectives are: I-developing an advanced and versatile platform which allows for the construction of miniaturized devices bringing together photonics/plasmonics and atomic vapours. II-exploring the science of light-vapour interactions at the nanoscale. III–exploiting the benefits and the uniqueness of our approach for mitigating challenging applications.
Two major platforms will be studied in great details. One is based on combining vapour cells with nanoscale dielectric waveguides and resonators, while the other consists of nanoscale plasmonic structures integrated with hot vapour cells. Using these platforms, plethora of physical effects will be studied and important applications will be demonstrated. Few examples include the study of atomic transitions near surfaces, weak and strong coupling between photonic and atomic resonant systems, slow and fast light effects, nonlinear optics, frequency standards and magnetometry. The proposed approach provides unique features, e.g. high optical densities, low power consumption, well-controlled coupling and small device footprint together with true chip scale integration. For example, owing to the enhanced light-vapour interaction and the small volume of the optical mode, it allows to explore few photons-few atoms interactions, with the ultimate goal of demonstrating effects in the single photon level regime.
Given the uniqueness of our approach, the successful implementation of the proposed research should provide an outstanding playground for conducting basic and applied research in the fields of nanophotonics, plasmonics and atomic physics, and will serve as a landmark for constructing novel miniaturized quantum devices.​

Prof. Yaakov Nahmias Institute of Life Sciences and Bioengineering, School of Computer Science & Engineering

​​Starting Grant (2009)
Project: Microfabrication-Based Rational Design of Transcriptional-Metabolic Intervention for the Treatment of Hepatitis C Virus (HCV) Infection
Consolidator Grant (2015)
Project: Tracking the Dynamics of Human Metabolism using Spectroscopy-Integrated Liver-on-Chip Microdevices​.

​​​​Summary (Starting Grant): Hepatitis C Virus (HCV) infection affects over 3% of the world population and is the leading cause of chronic liver disease worldwide. Current treatments are effective in only 50% of the cases and associated with significant side effects. Therefore, there is a pressing need for the development of alternative treatments. Recently, our group and others demonstrated that the HCV lifecycle is critically dependent on host lipid metabolism. In this context, we demonstrated that the grapefruit flavonoid naringenin blocks HCV production through PPAR± and LXR±, transcriptional regulators of hepatic lipid metabolism. While these results are promising, our ability to rationally control metabolic pathways in infected cells is limited due to an incomplete understanding of the regulation of hepatic metabolism by its underlying transcriptional network. This project aims to develop a comprehensive model of hepatic metabolism by integrating metabolic fluxes with transcriptional regulation enabling the rational design of transcriptional-interventions which will minimize HCV replication and release. Our approach is to develop two microfabricated platforms that will enable high-throughput data acquisition and a human-relevant screening. One component is the Transcriptional Activity Array (TAA), a microdevice for the high-throughput temporal acquisition of transcriptional activity data. The second is the Portal Circulation Platform (PCP) which integrates intestinal absorption module with a liver metabolism compartment enabling the high-throughput human-relevant screening of treatments as a substitute to animal experiments. This work will lead to the development of novel drug combinations for the treatment of HCV infection and impact the treatment of diabetes, obesity, and dyslipidemia.​

Summary (Consolidator Grant):The liver is the main organ responsible for the systemic regulation of human metabolism, responding to hormonal stimulation, nutritional challenges, and circadian rhythms using fast enzymatic processes and slow transcriptional mechanisms. This regulatory complexity limits our ability to create efficient pharmaceutical interventions for metabolic diseases such as fatty liver disease and diabetes. In addition, circadian changes in drug metabolism can impact pharmacokinetics and pharmacodynamics affecting our ability to optimize drug dosage or properly assess chronic liver toxicity.
The challenge in rationally designing efficient drug interventions stems from current reliance on end-point assays and animal models that provide intermittent information with limited human relevance. Therefore, there is a need to develop systems capable of tracking transcriptional and metabolic dynamics of human tissue with high-resolution preferably in real time. Over the past 5 years, we established state-of-the-art models of human hepatocytes; oxygen nanosensors; and cutting-edge liver-on-chip devices, making us uniquely suited to address this challenge.
We aim to develop a platform capable of tracking the metabolism of tissue engineered livers in real time, enabling an accurate assessment of chronic liver toxicity (e.g. repeated dose response) and the deconstruction of complex metabolic regulation during nutritional events. Our approach is to integrate liver-on-chip devices, with real time measurements of oxygen uptake, infrared microspectroscopy, and continuous MS/MS analysis. This innovative endeavour capitalizes on advances in nanotechnology and chemical characterization offering the ability to non-invasively monitor the metabolic state of the cells (e.g. steatosis) while tracking minute changes in metabolic pathways. This project has the short-term potential to replace animal models in toxicity studies and long-term potential to elucidate critical aspects in metabolic homeostasis.​

Prof. Nathalie Questembert-Balaban Institute of Physics, Faculty of Science

​​Starting Grant (2010)
Project: Genetic and phenotypic precursors of antibiotic resistance in evolving bacterial populations: from single cell to population level analyses
Consolidator Grant (2015)

Project: Evolution of antibiotic tolerance in the 'wild': A quantitative approach​


​​Summary (Starting Grant): Soon after new antibiotics are introduced, bacterial strains resistant to their action emerge. Recently, non-specific factors that promote the later appearance of specific mechanisms of resistance have been found. Some of these so-called global factors (as opposed to specific resistance mechanisms) emerge as major players in shaping the rate of evolution of resistance. For example, a mutation in the mismatch repair system is a global genetic factor that increases the mutation rate and therefore leads to an increased probability to evolve resistance. In addition to global genetic factors, it is becoming clear that global phenotypic factors play a crucial role in resistance evolution. For example, activation of stress responses can also result in an elevated mutation rate and accelerated evolution of drug resistance. A natural question which arises in this context is how sub-populations of phenotypic variants differ in their evolutionary potential, and how that, in turn, affects the rate at which an entire population adapts to antibiotic stress. I propose a multidisciplinary approach to the systematic and quantitative study of the non-specific factors that affect the mode and tempo of evolution towards antibiotic resistance. Our preliminary results indicate that the presence of dormant bacteria that survive antibiotic treatment affects the rate of resistance evolution in bacterial populations. I will exploit the established expertise of my lab using microfluidic devices for single cell analyses to track the emergence of resistance at the single-cell level, in real-time, and to study the correlation between the phenotype of single bacteria and the probability to evolve resistance. My second approach will take advantage of the recent developments in experimental evolution and high throughput sequencing and combine those with single cells observations for the systematic search of E.coli genes that affect the rate of resistance evolution. We will study replicate populations of E.coli, founded by either laboratory strains or clinical isolates, as they evolve in parallel, under antibiotic stress. Evolved populations will be compared with ancestral populations in order to identify genes and phenotypes that have changed during the evolution of antibiotic resistance. Finally, in silico evolution that simulates the experimental conditions will be developed to analyze the contribution of global factors on resistance evolution. The evolution of antibiotic resistance is not only a fascinating demonstration of the power of evolution but also represents one of the major health threats today. I anticipate that this multidisciplinary study of the global factors that influence the evolution of resistance, from the single cell to the population level, will shed light on the mechanisms used by bacteria to accelerate evolution in general, as well as provide clues as to how to prevent the emergence of antibiotic resistance.​

Summary (
Consolidator Grant): Bacterial ability to evolve strategies for evading antibiotic treatment is a fascinating example of an evolutionary process, as well as a major health threat. Despite efforts to understand treatment failure, we lack the means to prevent evolution of resistance when a new drug is released to the market. Most efforts are directed towards understanding the mechanisms of antibiotic resistance. Whereas ‘resistance’ is due to mutations that enable microorganisms to grow even at high concentrations of the drug, ‘tolerance’ is the ability to sustain a transient treatment, for example by entering a mode of transient dormancy. The importance of tolerance in the clinic has not been investigated as thoroughly as resistance. The presence of tolerant bacteria is not detected in the clinic because of the inherent difficulty of tracking dormant bacteria that often constitute only a minute fraction of the bacterial population. I hypothesize that bacterial dormancy may evolve quickly in the host under antibiotic treatment. This hypothesis is strengthened by our recent results demonstrating the rapid evolution of dormancy leading to tolerance in vitro, and by the increasing number of cases of treatment failure in the clinic not explained by resistance. My goal is to develop a multidisciplinary approach to detect, quantify and characterize tolerant bacteria in the clinic. Using my background in quantitative single-cell analyses, I will develop microfluidic devices for the rapid detection of tolerant bacteria in the clinic, systems biology tools to isolate and analyze dormant sub-populations directly from clinical isolates. I will search for the genetic mutations leading to tolerance, namely build what I term here the ‘tolerome’. The results will be analyzed in a mathematical framework of tolerance evolution. This approach should reveal the role of tolerance in the clinic and may lead to a paradigm shift in the way bacterial infections are characterized and treated.​

Dr. Oren Ram Institute of Life Science, Faculty of Science

Starting Grant (2016)
Project: Decoding the Epigenomic Regulatory Code by the Use of Single Cell Technologies​


Dr. Alex Retzker Institute of Physics, Faculty of Science

Consolidators Grant (2017)
Project:Transforming the limits of resolution by utilizing quantum information

Prof. Guy Ron Institute of Physics, Faculty of Science

​​Starting Grant (2016)
Project: Lab Based Searches for Beyond Standard Model Physics Using Traps

​​Summary: In this project I will measure a critical constant (beta-nu correlation) of the standard model to a precision of at least 0.1%, an order of magnitude improvement over the state of the art. The project will provide a platform for beyond standard-model (BSM) explorations, based on modern atom/ion trapping and a new accelerator facility.

High precision measurements of beta decay correlations in trapped radioactive atoms and ions are one of the most precise tools with which to search for BSM physics. The recently published US National Science Advisory Council 2015 Long Range Plan states: "Measurements of the decays of neutrons and nuclei provide the most precise and sensitive characterization of the charge-changing weak force of quarks and are a very sensitive probe of yet undiscovered new forces. In fact, weak decay measurements with an accuracy of 0.1% or better provide a unique probe of new physics at the TeV energy scale". Ne and He isotopes are particularly attractive due to calculable SM values, high sensitivity to several manifestations of BSM physics, ease of production, and lifetimes in the useful range for such experiments.

This program combines a Magneto-Optical Trap (MOT) and an Electrostatic Ion Beam Trap (EIBT) to perform a high-precision, competitive, measurement of correlations in the decay of such nuclei. The MOT program focuses on the neon isotopes, where existing measurements are of insufficient quality, and have unique sensitivities to aspects of BSM physics. The EIBT program focuses on measurements using 6He (where a comparison with existing measurements is of great import) and the aforementioned neon isotopes, allowing a direct comparison between the two systems within the same facility (a unique worldwide capability). The combination of these methods will allow an extraction of the beta-nu coefficient to the 0.1% level, making this proposal a forerunner in the field, which will provide a leap-step in the current set of world data.​

Prof. Eran Sharon Institute of Physics, Faculty of Science

Starting Grant (2009)
Project: Growth and Shaping of Soft Tissue

​​Summary: Many natural structures are made of soft tissue that undergoes complicated continuous shape transformations that accurately and reliably serve specific elaborate tasks. Such processes can be slow, as in growth of a tissue, leading from an initial, featureless, shape to the desired elaborate structure of the adult organ. In other cases continuous shape transformations of soft tissue are rapid and are used for the production of mechanical work, as in the case of the action of the hart. Our understanding of natural growth is limited and our ability to produce controlled motions of soft tissue is poor. A central problem in both cases is how to incorporate all local changes in the tissue in order to determine the mechanical state of the entire body. In addition, there are problems regarding how to measure a deforming body and how to characterize the deformation. Finally, there is a problem of how to control motion and growth in artificial and natural soft tissues. I propose a multi disciplinary study, based on an approach I have started developing. According to it there is an underlying common mathematical way to describe continuous large shape transformations of stretchable tissues. This approach clearly defines the way to determine the mechanical state of a deformed tissue and to measure its local growth/deformation. The project will involve a theoretical study within mechanics and differential geometry, an experimental-physics work, which will be focused on the construction of responsive deformable tissue elements and measurements of their shape evolution, and a biophysical work, in which the natural growth and motion of leaves will be measured and will be correlated with biological activities. Such an integrative study has the potential of advancing our understanding of the fascinating process of growth and to improve our ability to construct bio-inspired "soft machinery".

Dr. Hadar Steinberg Institute of Physics, Faculty of Science

​​Starting Grant (2014)
Project: Tunneling Spectroscopy in van-der-Waals Device​

​​Summary: I will expand the experimental reach of tunneling spectroscopy to new materials and device geometries. The technique is ideal for tackling two challenges: (i) Probing Andreev bound states and Majorana states in graphene and topological insulators (TIs) coupled to superconductors, and (ii) realizing momentum-conserving tunneling.
I will utilize a breakthrough in device fabrication to stack layered van-der-Waals materials, such as graphene and hexagonal Boron Nitride (hBN), to form vertical structures. Ultrathin layers of mechanically deposited dielectrics will be used as tunnel-barriers. These can interface any smooth surface, expanding the range of possible device-based tunneling systems.
A tunnel junction has decisive advantages over STM in access to lower temperatures and hence higher energy resolution. Significantly, the effort to probe the energy spectra of graphene and TIs coupled to superconductors is often resolution-limited. I will develop artificial-vortex devices and Josephson devices where induced spectra are expected to reveal the Majorana mode, a quantum state of unusual statistics sought as a platform for fault-tolerant quantum computation.
Using the same technology, I will develop devices where tunneling takes place between extended states. The aim is to realize momentum resolved tunneling for μeV-resolution measurement of dispersions in graphene, other 2D systems, and smooth interfaces. Momentum control will be achieved using density-tuning of the Fermi surfaces or using parallel magnetic field. The high resolution spectra will reveal details of interaction effects, manifest as modifications to the single-electron picture.
Carriers can be injected into a system with full control over their direction and energy – a powerful experimental knob, useful for injecting carriers using one electrode and extracting them in another. Such geometry is sensitive to relaxation effects, and will allow unprecedented resolution studies of out-of-equilibrium systems.​

Dr. Daniel Strasser Institute of Chemistry, Faculty of Science

Starting Grant (2012)
Project: Ultrafast EUV probe for Molecular Reaction Dynamics.

Summary: "This research is aimed at developing and validating a novel approach for time resolved imaging of structural dynamics, using single photon Coulomb explosion imaging (CEI) with ultrafast extreme UV (EUV) pulses to probe laser initiated ultrafast structural rearrangement and fragmentation dynamics. The emerging field of ultrafast EUV pulses attracts increasing amount of scientific attention, predominantly concentrated on understanding aspects of the generation process, as well as on measuring record breaking attosecond pulses at increasingly high photon energies and photon flux. I propose to direct the unique properties of ultrafast EUV pulses towards time resolved studies of molecular reaction dynamics that are inaccessible with conventional ultrafast laser systems. Time resolved single photon CEI will make possible the visualization of complex dynamics in polyatomic systems; specifically, how laser driven electronic excitation couples into nuclear motion in a wide range of molecular systems. In contrast to earlier attempts, in which CEI was driven with intense near-IR pulses that can alter the observed dynamics, the proposed single photon CEI will remove the masking intense field effects and provide a simple and general probe. A comprehensive experimental effort is proposed - to conduct a direct comparison of intense field CEI to the proposed single EUV photon approach. Successful implementation of this research will endow us with a new way to visualize and understand the underlying quantum mechanisms involved in chemical reactions. With this new technology I hope to be able to provide unique insight into molecular fragmentation and rearrangement dynamics during chemical reactions and to resolve long standing basic scientific questions, such as the concerted or sequential nature of double proton transfer in DNA base-pair models. Finally, the ""table top"" techniques developed in my lab will mature and become applicable to the emerging ultrafast EUV user facilities."

Dr. Yossi Tam Institute for Drug Research, Faculty of Medicine

​​Starting Grant (2015)
Project: From Peripheralized to Cell- and Organelle-Targeted Medicine: The 3rd Generation of Cannabinoid-1 Receptor Antagonists for the Treatment of Chronic Kidney Disease​

Summary: Clinical experience with globally-acting cannabinoid-1 receptor (CB1R) antagonists revealed the benefits of blocking CB1Rs for the treatment of obesity and diabetes. However, their use is hampered by increased CNS-mediated side effects. Recently, I have demonstrated that peripherally-restricted CB1R antagonists have the potential to treat the metabolic syndrome without eliciting these adverse effects. While these results are promising and are currently being developed into the clinic, our ability to rationally design CB1R blockers that would target a diseased organ is limited.
The current proposal aims to develop and test cell- and organelle-specific CB1R antagonists. To establish this paradigm, I will focus our interest on the kidney, since chronic kidney disease (CKD) is the leading cause of increased morbidity and mortality of patients with diabetes. Our first goal will be to characterize the obligatory role of the renal proximal tubular CB1R in the pathogenesis of diabetic renal complications. Next, we will attempt to link renal proximal CB1R with diabetic mitochondrial dysfunction. Finally, we will develop proximal tubular (cell-specific) and mitochondrial (organelle-specific) CB1R blockers and test their effectiveness in treating CKD. To that end, we will encapsulate CB1R blockers into biocompatible polymeric nanoparticles that will serve as targeted drug delivery systems, via their conjugation to targeting ligands.
The implications of this work are far reaching as they will (i) point to renal proximal tubule CB1R as a novel target for CKD; (ii) identify mitochondrial CB1R as a new player in the regulation of proximal tubular cell function, and (iii) eventually become the drug-of-choice in treating diabetic CKD and its comorbidities. Moreover, this work will lead to the development of a novel organ-specific drug delivery system for CB1R blockers, which could be then exploited in other tissues affected by obesity, diabetes and the metabolic syndrome.​

Prof. Itamar Willner Institute of Chemistry, Faculty of Science

Advanced Grant (2010)
Project: Nanoengineered Nanoparticles and Quantum Dots for Sensor and Machinery Applications

​​​​Summary: "Chemically modified metallic nanoparticles (NPs) or semiconductor quantum dots (QDs) are central components for the future development of nanotechnology and nanobiotechnology. This program aims to introduce new dimensions into the field of nanotechnology and nanobiotechnology by synthesizing, characterizing and assembling molecule- or biomolecule-modified nanoparticles (NPs)/Quantum dots (QDs) hybrid nanostructures that perform tailored and programmable functionalities. The project will include two complementary research activities. One direction will include the generation of electropolymerized ligand-functionalized Au NPs matrices on electrode surfaces. By tethering of appropriate ligands to the NPs, imprinted matrices for selective sensing, and signal-triggered NPs ""sponges"" for the selective uptake and release of substrates will be designed. Also, electrochemically induced pH changes by the NPs matrices will be used to control chemical reactivity (e.g., sol-gel transitions, activation of the ATP synthase machinery). The second research direction will implement ligand-modified QDs for the sensing of ions or molecular substrates. Similarly, nucleic acid-functionalized QDs will be used to develop new versatile sensing platforms exhibiting multiplexed analysis capabilities. One platform will include the quenching of the QDs by G-quadruplexes, whereas the second platform will use biochemiluminescence resonance energy transfer (BRET) as readout signal. Also, QDs-modified supramolecular DNA nanostructures will be designed to perform programmed machinery functions such as ""bi-pedal walker"", ""seesaw"", ""gear"" or ""tweezers"", and the machinery functions will be transduced by the optical properties of the QDs. Finally, DNA-machines that trigger the isothermal amplified replication of the analyzed nucleic acid will be designed, and QDs tethered to the machine will optically transduce the replication process at real-time."

Dr. Roie Yerushalmi Institute of Chemistry, Faculty of Science

Starting Grant (2010)
Project: Large Scale Architectures with Nanometric Structured Interfaces for Charge Separation, Transport and Interception

Summary: This research is aimed at developing new architectures at the molecular, nanometric, and macroscopic scales for the design and study of light induced charge transport using synthetic systems. The strategic objective is to establish a comprehensive approach for constructing nanometric scale hybrid structures that will enable us to tune the required physical, chemical, and electrical properties across scales required for efficient harvesting of light energy in a rigorous manner for enhancing our capabilities and basic understanding of light harvesting processes. We will form nanometric architectures featuring molecular diversity and functionality with nanometric gaps coupled to scaffolds capable of electrical transport. The nanometric architectures will be formed via simple yet powerful methods relying on sophisticated use of nanostructure surface chemistry and material properties while minimizing the application of top-down fabrication methods and will be studied at the single building block level as well as at array level. Meticulous study of the light induced charge separation and transport at the nanometric scale using single nanostructure building blocks as well as the collective dynamics of large scale arrays will be addressed with an emphasis on understanding charge dynamics at interfaces. The research activity will utilize unique nanostructure assembly methods and post-growth manipulation of the chemical composition developed during my research. Achieving our fundamental goals is expected to lead to new insights and capabilities relating to the harvesting of light energy and converting it to electrical energy and to significantly advance our ability to utilize light energy for photocatalysis.​

Dr. Alon Zaslaver Institute of Life Science, Faculty of Science

Starting Grant (2013)
Project: Design Principles in Encoding Complex Noisy Environments

Summary: Animals constantly face complex environments consisted of multiple fluctuating cues. Accurate detection and efficient integration of such perplexing information are essential as animals’ fitness and consequently survival depend on making the right behavioral decisions. However, little is known about how multifaceted stimuli are integrated by neural systems, and how this information flows in the neural network in a single-neuron resolution. Here we aim to address these fundamental questions using C. elegans worms as a model system. With a compact and fully-mapped neural network, C. elegans offers a unique opportunity of generating novel breakthroughs and significantly advance the field. To study functional dynamics on a network-wide scale with an unprecedented single-neuron resolution, we will construct a comprehensive library of transgenic animals expressing state-of-the-art optogenetic tools and Calcium indicators in individual neurons. Moreover, we will study the entire encoding process, beginning with the sensory layer, through integration in the neural network, to behavioral outputs. At the sensory level, we aim to reveal how small sensory systems efficiently encode the complex external world. Next, we will decipher the design principles by which neural circuits integrate and process information. The optogenetic transgenic animals will allow us interrogating computational roles of various circuits by manipulating individual neurons in the network. At the end, we will integrate the gathered knowledge to study how encoding eventually translates to decision making behavioral outputs. Throughout this project, we will use a combination of cutting-edge experimental techniques coupled with extensive computational analyses, modelling and theory. The aims of this interdisciplinary project together with the system-level approaches put it in the front line of research in the Systems Biology field.