ERC APPROVED PROJECTS WITH ISRAEL PARTICIPATION-2014

ERC Funded Projects - Israel - 2014
  • Rcn
    193418
    Nid
    14273
    Project acronym
    20SComplexity
    Project
    An integrative approach to uncover the multilevel regulation of 20S proteasome degradation
    Host Institution (HI)
    Weizmann Institute Of Science, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route. To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation: Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome. Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function. Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach. Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
    Website (HI)
    Max ERC funding
    1,500,000
    Duration
    Start date: 2015-04-01, End date: 2020-03-31
  • Rcn
    198161
    Nid
    14679
    Project acronym
    BNYQ
    Project
    Breaking the Nyquist Barrier: A New Paradigm in Data Conversion and Transmission
    Host Institution (HI)
    Technion Israel Institute Of Technology, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    Digital signal processing (DSP) is a revolutionary paradigm shift enabling processing of physical data in the digital domain where design and implementation are considerably simplified. However, state-of-the-art analog-to-digital convertors (ADCs) preclude high-rate wideband sampling and processing with low cost and energy consumption, presenting a major bottleneck. This is mostly due to a traditional assumption that sampling must be performed at the Nyquist rate, that is, twice the signal bandwidth. Modern applications including communications, medical imaging, radar and more use signals with high bandwidth, resulting in prohibitively large Nyquist rates. Our ambitious goal is to introduce a paradigm shift in ADC design that will enable systems capable of low-rate, wideband sensing and low-rate DSP. While DSP has a rich history in exploiting structure to reduce dimensionality and perform efficient parameter extraction, current ADCs do not exploit such knowledge. We challenge current practice that separates the sampling stage from the processing stage and exploit structure in analog signals already in the ADC, to drastically reduce the sampling and processing rates. Our preliminary data shows that this allows substantial savings in sampling and processing rates --- we show rate reduction of 1/28 in ultrasound imaging, and 1/30 in radar detection.   To achieve our overreaching goal we focus on three interconnected objectives -- developing the 1) theory 2) hardware and 3) applications of sub-Nyquist sampling. Our methodology ties together two areas on the frontier of signal processing: compressed sensing (CS), focused on finite length vectors, and analog sampling. Our research plan also inherently relies on advances in several other important areas within signal processing and combines multi-disciplinary research at the intersection of signal processing, information theory, optimization, estimation theory and hardware design.
    Website (HI)
    Max ERC funding
    2,400,000
    Duration
    Start date: 2015-08-01, End date: 2020-07-31
  • Rcn
    194524
    Nid
    13967
    Project acronym
    Brain circRNAs
    Project
    Rounding the circle: Unravelling the biogenesis, function and mechanism of action of circRNAs in the Drosophila brain.
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    Tight regulation of RNA metabolism is essential for normal brain function. This includes co and post-transcriptional regulation, which are extremely prevalent in neurons. Recently, circular RNAs (circRNAs), a highly abundant new type of regulatory non-coding RNA have been found across the animal kingdom. Two of these RNAs have been shown to act as miRNA sponges but no function is known for the thousands of other circRNAs, indicating the existence of a widespread layer of previously unknown gene regulation. The present proposal aims to comprehensively determine the role and mode of actions of circRNAs in gene expression and RNA metabolism in the fly brain. We will do so by studying their biogenesis, transport, and mechanism of action, as well as by determining the roles of circRNAs in neuronal function and behaviour. Briefly, we will: 1) identify factors involved in the biogenesis, localization, and stabilization of circRNAs; 2) determine neuro-developmental, molecular, neural and behavioural phenotypes associated with down or up regulation of specific circRNAs; 3) study the molecular mechanisms of action of circRNAs: identify circRNAs that work as miRNA sponges and determine whether circRNAs can encode proteins or act as signalling molecules and 4) perform mechanistic studies in order to determine cause-effect relationships between circRNA function and brain physiology and behaviour. The present proposal will reveal the key pathways by which circRNAs control gene expression and influence neuronal function and behaviour. Therefore it will be one of the pioneer works in the study of this new and important area of research, which we predict will fundamentally transform the study of gene expression regulation in the brain
    Website (HI)
    Max ERC funding
    1,971,750
    Duration
    Start date: 2016-02-01, End date: 2021-01-31
  • Rcn
    193676
    Nid
    14091
    Project acronym
    CLC
    Project
    Cryptography with Low Complexity
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    The efficiency of cryptographic constructions is a fundamental question. Theoretically, it is important to understand how much computational resources are needed to guarantee strong notions of security. Practically, highly efficient schemes are always desirable for real-world applications. More generally, the possibility of cryptography with low complexity has wide applications for problems in computational complexity, combinatorial optimization, and computational learning theory.   In this proposal we aim to understand what are the minimal computational resources needed to perform basic cryptographic tasks. In a nutshell, we suggest to focus on three main objectives. First, we would like to get better understanding of the cryptographic hardness of random local functions. Such functions can be computed by highly-efficient circuits and their cryptographic hardness provides a strong and clean formulation for the conjectured average-case hardness of constraint satisfaction problems - a fundamental subject which lies at the core of the theory of computer science. Our second objective is to harness our insights into the hardness of local functions to improve the efficiency of basic cryptographic building blocks such as pseudorandom functions. Finally, our third objective is to expand our theoretical understanding of garbled circuits, study their limitations, and improve their efficiency.   The suggested project can bridge across different regions of computer science such as random combinatorial structures, cryptography, and circuit complexity. It is expected to impact central problems in cryptography, while enriching the general landscape of theoretical computer science.
    Max ERC funding
    1,265,750
    Duration
    Start date: 2015-05-01, End date: 2020-04-30
  • Rcn
    193495
    Nid
    14249
    Project acronym
    CNIDARIAMICRORNA
    Project
    Elucidation of the evolution of post-transcriptional regulation by characterizing the cnidarian microRNA pathway
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    Over the past decade small RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) have been shown to carry pivotal roles in post-transcriptional regulation and genome protection and to play an important part in various physiological processes in animals. miRNAs can be found in a very wide range of animals yet their functions were studied almost exclusively in members of the Bilateria such as insects, nematodes and vertebrates. Hence studying their function in representatives of non-bilaterian phyla such as Cnidaria (sea anemones, corals, hydras and jellyfish) is crucial for understanding the evolution of miRNAs in animals and can provide important insights into their roles in the ancient ancestor of Cnidaria and Bilateria. The sea anemone Nematostella vectensis is an excellent model for such a study since it can be grown in large numbers throughout its life cycle in the lab and because well-established genetic manipulation techniques are available for this species. Our preliminary results indicate that miRNAs in Nematostella frequently have a nearly perfect match to their messenger RNA (mRNA) targets, resulting in cleavage of the target. This mode of action is common for plant miRNAs, but is very rare in Bilateria. This finding together with my recent discovery of a Nematostella homolog of HYL1, a protein involved in miRNA biogenesis in plants, raises the exciting possibility that the miRNA pathway existed in the common ancestor of plants and animals. Here I suggest to bring together an array of advanced biochemical and genetic methods such as gene knockdown, transgenesis, high throughput sequencing and immunoprecipitation in order to obtain - for the first time - a deep understanding of the biogenesis and mechanism of action of small RNAs in Cnidaria. This will provide a novel way to understand the evolution of this important molecular pathway and to evaluate its age and ancestral form.
    Website (HI)
    Max ERC funding
    1,499,587
    Duration
    Start date: 2015-05-01, End date: 2020-05-01
  • Rcn
    197227
    Nid
    14390
    Project acronym
    CONC-VIA-RIEMANN
    Project
    High-Dimensional Convexity, Isoperimetry and Concentration via a Riemannian Vantage Point
    Host Institution (HI)
    Technion Israel Institute Of Technology, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    "In recent years, the importance of superimposing the contribution of the measure to that of the metric, in determining the underlying space's (generalized Ricci) curvature, has been clarified in the works of Lott, Sturm, Villani and others, following the definition of Curvature-Dimension introduced by Bakry and Emery. We wish to systematically incorporate this important idea of considering the measure and metric in tandem, in the study of questions pertaining to isoperimetric and concentration properties of convex domains in high-dimensional Euclidean space, where a-priori there is only a trivial metric (Euclidean) and trivial measure (Lebesgue).   The first step of enriching the class of uniform measures on convex domains to that of non-negatively curved ("log-concave") measures in Euclidean space has been very successfully implemented in the last decades, leading to substantial progress in our understanding of volumetric properties of convex domains, mostly regarding concentration of linear functionals. However, the potential advantages of altering the Euclidean metric into a more general Riemannian one or exploiting related Riemannian structures have not been systematically explored. Our main paradigm is that in order to progress in non-linear questions pertaining to concentration in Euclidean space, it is imperative to cast and study these problems in the more general Riemannian context.   As witnessed by our own work over the last years, we expect that broadening the scope and incorporating tools from the Riemannian world will lead to significant progress in our understanding of the qualitative and quantitative structure of isoperimetric minimizers in the purely Euclidean setting. Such progress would have dramatic impact on long-standing fundamental conjectures regarding concentration of measure on high-dimensional convex domains, as well as other closely related fields such as Probability Theory, Learning Theory, Random Matrix Theory and Algorithmic Geometry."
    Website (HI)
    Max ERC funding
    1,194,190
    Duration
    Start date: 2015-10-01, End date: 2020-09-30
  • Rcn
    194999
    Nid
    13932
    Project acronym
    Cancer-Drug-Screen
    Project
    High-throughput drug screening for identifying personalized cancer treatments tailored to the particular mutations of the patient’s tumor
    Host Institution (HI)
    Weizmann Institute Of Science, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    Cancer is caused by a series of genetic alterations that confer an advantage to cancer cells, leading to uncontrolled growth. However, each tumor exhibits distinct molecular changes, making each patient’s malignancy unique. Hence, in the personalized medicine era, cancer treatment aims to tailor the most suitable treatment for each patient according to his/her genetic background, tumor acquired mutations and clinical indications.   The p53 tumor suppressor is the most frequently mutated gene in human cancers, with thousands of different tumor-associated mutations reported. Many such cancer-associated mutations in p53 lead to loss of its tumor suppressive activity and in some cases, to gain of new oncogenic functions, resulting in tumor recurrence and enhanced patient mortality. Importantly, tumors with different p53 mutations exhibit specific cancerous phenotypes and do not respond to particular treatments.   Based on our ERC-funded breakthrough technology, where we made a library of ~10,000 distinct p53 variants, and based on our strong IPR offering and competitive advantages, here we propose to develop three products for determining which treatment (or combination) would be most effective for treating a patient’s tumor according to his specific p53 sequence, reducing excruciating side effects and improving treatment outcomes: 1) Offering patients/physicians a list of treatments ranked by their efficacy in treating cells of similar origin and p53 mutations to those present in the patient’s tumor, allowing them to make more informed treatment decisions. 2) Offering companies in the personalized cancer treatment field access to our existing proprietary data regarding treatment efficacies towards p53 genetic variants. 3) A service to drug developing companies that applies our technology for testing the efficacy of a client-supplied drug of interest over all ~10,000 p53 mutations in our library in a cell-line of choice.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-04-01, End date: 2016-09-30
  • Rcn
    193784
    Nid
    14049
    Project acronym
    Cancer-Targeted PolyIC
    Project
    Treatment of EGFR over-expressing cancers by targeted non-viral delivery of PolyIC
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    We have recently shown that application of EGFR targeted synthetic dsRNA: Poly Iosine/Poly Cytosine (pIC) is highly efficient and selective against deadly cancers overexpressing EGFR, like glioblastoma (U87MGwtEGFR), breast cancer (MDA-MB-468) and adenocarcinoma (A431). Double-stranded RNA, frequently expressed in cells infected with viruses, activates a number of pro-apoptotic processes simultaneously. These dsRNA-induced mechanisms efficiently kill infected cells and induce expression of anti-proliferative cytokines from the interferon (IFN) family, thereby preventing spread of the virus. pIC delivered with Melittin-polyethylenimine-polyethyleneglycol-EGF (MPPE) eliminated orthotropic and subcutaneous tumors of the above cancers. Heterogeneous glioblastoma models where only half of the cells overexpress wtEGFR are also eliminated by local application, most likely due to a bystander antiproliferative effects, at least partially mediated by interferons (Shir et al., 2006). Systemic application of EGFR targeted pIC is also highly effective against breast and adenocarcinoma disseminated cancer models resembling metastatic cancers (Shir et al., 2011). During the last two years we have improved the vectors homing to EGFR to entities that can now be translated into clinical agents (Shaffert, 2011; Shir 2011, Abourbeh 2012). The impressive results with these more simplified vectors, make this project ready for clinical development, which requires fund raising from a Company/Venture capitalist. Commercialization of the therapy will be detailed in the proposal.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-02-01, End date: 2016-07-31
  • Rcn
    193787
    Nid
    14047
    Project acronym
    ContactLube
    Project
    Highly-lubricated soft contact lenses
    Host Institution (HI)
    Weizmann Institute Of Science, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    The object of this proof of concept project is to modify soft contact lenses to render them more lubricated, and so make them far more comfortable to use. We propose to improve greatly the lubricity of soft contact lenses, used by over 100 million people worldwide with a market of around $7.5bn, and for which acute discomfort may arise from high friction at the interfaces between the lenses and the eyelid or cornea. According to an established clinical hypothesis, ocular comfort is related to the level of friction between the anterior side of the contact lens and the inner eyelid occurring during the blinking process, and boundary lubrication is the key to providing user comfort during extensive wearing of soft contact lenses. High lens friction, for a substantial part of the user population, can limit the extent to which soft lenses may be used and can also aggravate pathologies such as dry eye syndrome. Thus soft contact lenses that are much better lubricated than those currently in use have clear economic and health-related benefits. The current project, working through 5 work-packages, will establish the feasibility, will carry out competitive analysis, explore the commercialization process and the IPR position, and seek contacts with appropriate industrial partners to further develop the commercialization of this idea.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-01-01, End date: 2016-06-30
  • Rcn
    193738
    Nid
    14069
    Project acronym
    DCM
    Project
    Distributed Cryptography Module
    Host Institution (HI)
    Bar Ilan University, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    The DCM (Distributed Crypto Module) is a unique security system that provides a significant boost in server-side security, which will benefit almost every organisation today. The technology relies on a novel approach to protect cryptographic keys and authentication credentials that form the backbone of network and data security. Currently, the cryptographic keys and authentication credentials that reside on servers inside networks constitute single points of failure: it suffices for the attacker to obtain them and all is lost. This is due to the fact that all cryptographic techniques rely on the secrecy of the key; if the key is compromised then all is lost. Indeed, cryptography is rarely broken (even by the NSA); rather, it is bypassed by stealing the key! Server breaches are ubiquitous today and novel defenses are an acute need today in industry and government.   In the DCM, the key is first split and shared amongst two or more servers (using known secret sharing technology) and then using our novel approach, the cryptographic operations necessary are carried out without bringing the parts of the secret together. Rather, the servers run a secure protocol, based on secure multiparty computation, which has the security guarantee that even if an attacker breaks into all but one of the servers, and can run any malicious code that it wishes, it still cannot learn anything about the secret key or credential. By configuring the DCM servers independently (different OS, different admins, different defenses, etc.), a very high level of security is achieved. The scope of the Proof of Concept DCM encapsulates the steps need to bring this groundbreaking technology to the market. A full business plan and market survey will be developed for the construction of a new company that will develop the DCM application and bring it to market. The first full version of a DCM will be ready for market a year after the company has been established (with limited versions earlier).
    Website (HI)
    Max ERC funding
    149,776
    Duration
    Start date: 2014-11-01, End date: 2016-04-30

  Rcn

  • 193785
    Nid
    14048
    Project acronym
    EDUCAGE
    Project
    The EDUCAGE: A Behavioral Platform for Naturalistic Learning
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    Understanding behavior is still one of the holy grails in the natural and social sciences. Behavior is often utterly complex because it is a result of an extremely rich set of past experiences, the present state of the animal and the animal’s predictions about the future; all of which affect learning, decision making and consequently behavior. Given the complexity of behavior, most researchers work in the realm of highly simplified learning tasks but these only test very basic attributes of learning and are constraining discovery of more sophisticated behavior. To date, there are only few available platforms for rigorous study of complex behavioral paradigms in experimental animals; not in basic science nor in biomedical research. Our goal is to bring to completion (and potential commercialization) a novel platform for analyzing complex animal behavior named "The Educage" to allow fully automatic, hands free assessment of higher cognitive functions in freely behaving animals. Potential customers are research labs, and the biomedical industry. The Educage will allow researchers to study behavior at unprecedented resolution, 24/7, for any duration of time. The learning paradigms can be tailored to the specific task of interest. The Educage has many advantages that outperform existing technologies by allowing rigorous statistical assessment of complex behaviors in laboratory animals. The Educage allows researchers the flexibility to monitor, analyze and manipulate the experiment during the behavior. Our system can be reliably used to analyze perceptual learning in mice and is well suited for being a new and rigorous behavioral platform. It has great potential to become a central tool to fuel discovery in animal research both in biology and biomedical research.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-01-01, End date: 2016-06-30
  • Rcn
    193239
    Nid
    14283
    Project acronym
    EXTPRO
    Project
    Quasi-Randomness in Extremal Combinatorics
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    Combinatorics is an extremely fast growing mathematical discipline. While it started as a collection of isolated problems that were tackled using ad-hoc arguments it has since grown into a mature discipline which both incorporated into it deep tools from other mathematical areas, and has also found applications in other mathematical areas such as Additive Number Theory, Theoretical Computer Science, Computational Biology and Information Theory.   The PI will work on a variety of problems in Extremal Combinatorics which is one of the most active subareas within Combinatorics with spectacular recent developments. A typical problem in this area asks to minimize (or maximize) a certain parameter attached to a discrete structure given several other constrains. One of the most powerful tools used in attacking problems in this area uses the so called Structure vs Randomness phenomenon. This roughly means that any {\em deterministic} object can be partitioned into smaller quasi-random objects, that is, objects that have properties we expect to find in truly random ones. The PI has already made significant contributions in this area and our goal in this proposal is to obtain further results of this caliber by tackling some of the hardest open problems at the forefront of current research. Some of these problems are related to the celebrated Hypergraph and Arithmetic Regularity Lemmas, to Super-saturation problems in Additive Combinatorics and Graph Theory, to problems in Ramsey Theory, as well as to applications of Extremal Combinatorics to problems in Theoretical Computer Science. Another major goal of this proposal is to develop new approaches and techniques for tackling problems in Extremal Combinatorics.   The support by means of a 5-year research grant will enable the PI to further establish himself as a leading researcher in Extremal Combinatorics and to build a vibrant research group in Extremal Combinatorics.
    Max ERC funding
    1,221,921
    Duration
    Start date: 2015-03-01, End date: 2020-02-29
  • Rcn
    193647
    Nid
    14119
    Project acronym
    FLDcure
    Project
    A potent Micro-RNA therapeutic for nonalcoholic fatty liver disease (NAFLD)
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    Fatty Liver disease (FLD) is a widespread disease which can often progress to Nonalcoholic steatohepatitis, cirrhosis and liver cancer. At present FLD disease affects a huge perportion of the population and prompt treatment will be of major health benefits to the general population. We have developed a specific therapeutic targeting a microRNA we and others have shown to be involved in the pathogenesis of FLD. This therapeutic agent can dramatically reduce FLD in a mouse model. We would like to extend the pre-clinical studies in order to encourage interest of a pharmaceutical company who will license the technology and pursue clinical trials.
    Website (HI)
    Max ERC funding
    149,800
    Duration
    Start date: 2015-01-01, End date: 2016-06-30
  • Rcn
    193557
    Nid
    14196
    Project acronym
    FOC
    Project
    Foundations of Cryptographic Hardness
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    A fundamental research challenge in modern cryptography is understanding the necessary hardness assumptions required to build different cryptographic primitives. Attempts to answer this question have gained tremendous success in the last 20-30 years. Most notably, it was shown that many highly complicated primitives can be based on the mere existence of one-way functions (i.e., easy to compute and hard to invert), while other primitives cannot be based on such functions. This research has yielded fundamental tools and concepts such as randomness extractors and computational notions of entropy. Yet many of the most fundamental questions remain unanswered. Our first goal is to answer the fundamental question of whether cryptography can be based on the assumption that P not equal NP. Our second and third goals are to build a more efficient symmetric-key cryptographic primitives from one-way functions, and to establish effective methods for security amplification of cryptographic primitives. Succeeding in the second and last goals is likely to have great bearing on the way that we construct the very basic cryptographic primitives. A positive answer for the first question will be considered a dramatic result in the cryptography and computational complexity communities. To address these goals, it is very useful to understand the relationship between different types and quantities of cryptographic hardness. Such understanding typically involves defining and manipulating different types of computational entropy, and comprehending the power of security reductions. We believe that this research will yield new concepts and techniques, with ramification beyond the realm of foundational cryptography.
    Max ERC funding
    1,239,838
    Duration
    Start date: 2015-03-01, End date: 2020-02-29
  • Rcn
    197837
    Nid
    14551
    Project acronym
    GV-FLU
    Project
    A Genetic View of Influenza Infection
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    Inherited variation in the quantity and functionality of immune cells plays a key role in determining phenotypic diversity between individuals. Surprisingly little is known, however, about the specific contribution of immune cell subsets to variation in phenotypes such as susceptibility to infectious diseases and the underlying genetic variation. In many complex diseases, we currently have a poor understanding of the driver cell types that are responsible for inherited variation in disease states. A comprehensive mapping of quantities and functions of immune cell types during the course of disease, in large cohorts, bears the potential to transform genetic research; provides understanding of the genetic and immune basis of phenotypes; and reveals the key driver cell subsets.   Here I aim to derive a mechanistic understanding of how variation in quantity and function of immune cell subsets mediates inherited variation in disease states. I propose to develop a computational model that integrates predicted quantities and functions of cell subsets with genotypic and phenotypic information, leading to specific hypotheses on physiological regulation and the particular cell subsets that drive phenotypic diversity. To circumvent the technical difficulty in quantifying a large number of immune cell types, I will profile gene expression and computationally quantify changes in a large number of cell types. I will develop and apply this strategy to dissect Influenza infection in mice.   Since changes in immune responses play a key role in complex diseases, our ability to predict variation in immune responses from genotypes would have important clinical implications. This project has far reaching implications as the paradigm developed here will transform quantitative genetics studies as well as systems immunology research of complex disease. This approach will be applicable to any mammalian disease, allowing researchers to dissect their own systems at unprecedented detail.
    Max ERC funding
    1,497,000
    Duration
    Start date: 2015-07-01, End date: 2020-06-30
  • Rcn
    197450
    Nid
    14355
    Project acronym
    HAS
    Project
    Harmonic Analysis and l-adic sheaves
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Advanced Grant (AdG), ERC-2014-ADG
    Summary
    "In recent years there has been impressive development of the higher category theory and in particular development of the categorical counterpart of the Langlands conjecture over fields of finite characteristic. But until now, this development has had little bearing on the classical problems which deal with spaces of functions. The main goal of this proposal is to build the technique to apply the category theory to classical problems. Of course on the way I will have to deal with problems in the categorical realm.   The first part of the proposal deals with construction of characters of irreducible representations of reductive groups over local nonarchimedian fields F in terms of traces of the Frobenious endomorphisms which should lead to the proof of the "Stable center conjecture" at least for representations of depth zero.   The second part is on the extension of the definition of L-functions of representations of reductive F-groups corresponding to an arbitrary representation of the dual groups. As it is now, the definition is known only for very special representations of the dual group and only in the case of classical groups.   The third part is on the extension of the classical theory to representations of Kac-Moody groups over local fields."
    Website (HI)
    Max ERC funding
    1,569,488
    Duration
    Start date: 2015-10-01, End date: 2020-09-30
  • Rcn
    199670
    Nid
    15275
    Project acronym
    HoloVision
    Project
    Advanced holographic optical neural stimulation for vision restoration and basic research
    Host Institution (HI)
    Technion Israel Institute Of Technology, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    When natural sensory input is disrupted, as in outer-retinal degenerative diseases, artificial stimulation of surviving nerve cells offers a potential strategy for bypassing compromised neural circuits and substituting sensory perception. Current neuro-stimulation interfaces that use electrical currents from micro-electrode arrays are already being clinically applied for retinal stimulation, but their performance is ultimately limited by current spread and the requirement for physical contact with an implanted device. Future minimally-invasive systems could use light patterns to photo-induce complex yet precise spatio-temporal activity patterns among surviving retinal neurons, with the ultimate potential of restoring vision to a nearly normal level. Here, we will advance, optimize and test in vivo a powerful new strategy for cellular-resolution controlled patterned optogenetic excitation, based on computer-generated holographic optical neural-stimulation (HONS). Regular (one-photon) HONS systems can dynamically address large populations of optogenetically-transduced retinal ganglion cells with single-cell resolution, while related multiphoton HONS systems can extend these capabilities to three-dimensional cortical tissue (relevant to many research applications). A series of in vivo experiments will resolve basic questions regarding the efficacy of these approaches by directly examining the retinal and cortical responses to structured holographic photo-stimulation, and test novel strategies for improving it. Finally, as a major step towards clinical translation of this technology, we will design and evaluate (in blind sheep and sighted individuals) a human-scale prototype. Overall, by combining both basic and translational research, this study will advance novel optical neuro-technologies with potential impact on multiple scientific and clinical applications. Specifically, it will tackle the major engineering requirements and constraints towards the development of a
    Website (HI)
    Max ERC funding
    2,624,517
    Duration
    Start date: 2016-01-01, End date: 2020-12-31
  • Rcn
    193661
    Nid
    14106
    Project acronym
    InfoInt
    Project
    An Information Theory of Simple Interaction
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    Motivated by our recent progress in feedback information theory and its deep relations to stochastic dynamical systems, and inspired by natural phenomena such as bio-molecular interactions and human conversation, this research will explore the fundamental limits of information transfer via simple interaction. In the standard information theoretic framework, the problem of reliable communications is typically studied in an asymptotic unidirectional regime, where optimal performance is attained via complex codes employed over increasingly long time epochs. Here, we will investigate a markedly different paradigm where communicating parties are restricted to use simple finite-state rules to act and react on the fly. We will consider a broad spectrum of models ranging from feedback communications and two-way channels to multiuser setups and large homogeneous networks, and study measures of information transfer and dissipation, their relations to dynamical system contraction factors, and the fundamental tradeoffs between complexity and performance. While prominently theoretic, our investigation is expected to admit important practical applications and a cross-disciplinary impact. In communications, and especially in resource-limited systems such as wireless sensor networks where battery-life is a bottleneck, a breakthrough in the understanding of optimal interaction can lead to a paradigm shift in system design, yielding simpler, cheaper, more robust solutions. In Finance, where market behavior is a cumulative effect of local actions taken by individuals based on limited noisy observations, quantifying interaction and its relation to information propagation can enhance our ability to forecast and explain macro level phenomena. Finally, an information theoretic characterization of interaction in large networks can shed light on the underlying mechanisms governing various biological systems that are empirically amenable to cellular automata modeling.
    Max ERC funding
    1,323,875
    Duration
    Start date: 2015-03-01, End date: 2020-02-29
  • Rcn
    199663
    Nid
    15282
    Project acronym
    JCR
    Project
    Judicial Conflict Resolution: Examining Hybrids of Non-adversarial Justice
    Host Institution (HI)
    Bar Ilan University, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    In the past few decades, the role of judges has changed dramatically and its nature has remained largely unexplored. To date, most cases settle or reach plea-bargaining, and the greater part of judges’ time is spent on managing cases and encouraging parties to reach consensual solutions. Adjudication based on formal rules is a rare phenomenon which judges mostly avoid. The hypothesis underlying JCR is that the various Conflict Resolution methods which are used outside the courtroom, as alternatives to adjudication, could have a strong and positive influence, both theoretical and practical, on judicial activities inside the courts. Judicial activities may be conceptualised along the lines of generic modes of conflict resolution such as mediation and arbitration. Judicial conflict resolution activity is performed in the shadow of authority and in tension with it, and crosses the boundaries between criminal and civil conflicts. It can be evaluated, studied and improved through criteria which go beyond the prevalent search for efficiency in court administration. Empirically, JCR will study judicial activities in promoting settlements comparatively from a quantitative and qualitative perspective, by using statistical analysis, in-depth interviews, mapping and framing legal resources, court observations and narrative analysis. Theoretically, JCR will develop a conflict resolution jurisprudence, which prioritises consent over coercion as a leading value for the administration of justice. Prescriptively, JCR will promote a participatory endeavour to build training programs for judges that implement the research findings regarding the judicial role. Following such findings, JCR will also consider generating recommendations to change legal rules, codes of ethics, measures of evaluation, and policy framings. JCR will increase accountability and access to justice by introducing coherence into a mainstream activity of processing legal conflicts.
    Website (HI)
    Max ERC funding
    1,272,534
    Duration
    Start date: 2016-01-01, End date: 2020-12-31
  • Rcn
    196872
    Nid
    13790
    Project acronym
    LIVIN
    Project
    Light-Vapour Interactions at the Nanoscale
    Host Institution (HI)
    The Hebrew University Of Jerusalem, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    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.
    Website (HI)
    Max ERC funding
    1,998,863
    Duration
    Start date: 2015-06-01, End date: 2020-05-31
  • Rcn
    198445
    Nid
    14744
    Project acronym
    LeukoTheranostics
    Project
    Harnessing Targeted Nanotheranostics to Reprogram Activated Leukocytes in Inflammatory Bowel Disease
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    "Inflammatory bowel diseases (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease (CD) and Ulcerative Colitis (UC) that can impact both the large and small bowel. IBD affects approximately 3.7 million Europeans and its peak onset is in persons of 15 to 30 years of age. IBD imposes a significant burden on Europe with over €3B in annual health care costs and over €3B in indirect cost. The prevalence of IBD is expected to increase by more than 40% over the next decade in many European countries. Therefore, to meet the needs of IBD patients in the European community, we must prepare for the evolving landscape of IBD care in the near future. Although its etiology remains unknown, unregulated immune cells are implicated in the pathogenesis of IBD. As many IBD patients are refractory to conventional medical treatments, there is an urgent need to develop novel therapeutic modalities in combination with real-time imaging in order to manage the disease. I will achieve this goal by generating a "Trojan horse" strategy of targeting activated leukocytes that home to the gut in IBD rodent models and reprogram their fate using RNA interference (RNAi) combined with molecular imaging. The primary objective of this proposal is to reprogram in vivo activated leukocytes involved in gut inflammation using advanced RNAi-based therapeutics combined with molecular imaging strategies as the first theranostic modality utilizing leukocytes. The following specific aims include: (i) To develop and characterize unique integrin-targeted nanoparticles (I-tsNPs) targeting a high-affinity (HA) conformation of a4b7 integrin expressed on gut leukocytes; (ii) To study I-tsNPs 3-dimensional (3-D) delivery in colitis models using microPET/CT imaging; (iii) To investigate efficacy and safety profiles using the HA I-tsNPs platform for IBD therapeutics and disease management that will lay the foundation for future clinical trials."
    Website (HI)
    Max ERC funding
    2,703,125
    Duration
    Start date: 2015-11-01, End date: 2020-10-31
  • Rcn
    198228
    Nid
    14627
    Project acronym
    LineageDiscovery
    Project
    Laying the Biological, Computational and Architectural Foundations for Human Cell Lineage Discovery
    Host Institution (HI)
    Weizmann Institute Of Science, Israel
    Call details
    Advanced Grant (AdG), ERC-2014-ADG
    Summary
    Within a decade, advances in single-cell genomics would allow humanity to embark on a coordinated international effort to discover the human cell lineage tree. The goal of LineageDiscovery is to lay the biological, computational and architectural foundations for this envisioned project and demonstrate its feasibility and value. An organismal cell lineage tree is a rooted, labelled binary tree where nodes represent organism cells, edges represent progeny relations and labels capture cell state. The tree of an adult human has about 100 trillion nodes. Many fundamental open questions in biology and medicine are about the structure, dynamics and variance of the human cell lineage tree in development, health, ageing and disease. E.g., which cancer cells give rise to metastases? Do beta cells renew? Which progeny do brain stem cells produce in development, maintenance and ageing? LineageDiscovery is based on a decade of research on this challenge by Shapiro’s lab and others. It will develop an efficient biological-computational cell lineage discovery workflow that starts with sampled cells and ends with knowledge of their cell lineage tree; and a scalable architecture for the collaborative development and the distributed deployment of this workflow. The workflow will be based on emerging single-cell technologies and will include novel algorithms to analyse single-cell data, to reconstruct cell lineage trees, and to infer ancestral cell type and state dynamics. A programmable meta-system will be developed and used for workflow optimization and evaluation. The workflow and architecture will be deployed and tested in a broad range of proof-of-concept human cell lineage discovery experiments with self-funded collaborators. Successful execution of this research plan coupled with expected advances in single-cell genomics would establish both the feasibility and the value of the envisioned large-scale human cell lineage discovery project, ideally leading to its launch.
    Website (HI)
    Max ERC funding
    2,250,000
    Duration
    Start date: 2015-09-01, End date: 2020-08-31
  • Rcn
    193398
    Nid
    13890
    Project acronym
    LuMaSense
    Project
    A Non-Invasive Test for Guiding Follow–up of Patients with CT-Detected Lung Nodules
    Host Institution (HI)
    Technion Israel Institute Of Technology, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    This PoC is a commercially-oriented spin-off from our "DIAG-CANCER" ERC project, addressing an urgent clinical need in the field of lung cancer (LC). The rationale behind this PoC is that CT-based LC screening programs are emerging in many countries worldwide. However, the high false positive rate of this technique (96% out of the 24% positive CT findings are non-cancerous) has been a major challenge in front those plans. This is because the CT-detected non-cancerous group has undergone unnecessary invasive procedures that are both costly and associated with significant morbidity and mortality. With this PoC project, we aim to increase the specificity of the LDCT based screening program by utilizing an auxiliary noninvasive breath test to distinguish between malignant and non-cancerous CT findings. The proposed breath test relies on a novel stand-alone device that provide an improved combination of speed, sensitivity, portability, low complexity, easy operation and low production cost. In order to transform our idea and current technology into a marketable device we propose taking several steps: (i) optimization of a prototype device and evaluation of its clinical usefulness through clinical studies; (ii) completing the IP portfolio of the device; and (iii) conducting detailed market research to identify the optimal placement in the healthcare market and possible competitors. After completing these stages, to be covered by the present grant, we propose to proceed to the technology transfer to a mature health care company or through complementary fund to advance the technological plans. If successful, the proposed PoC can be translated immediately into a powerful tool for the management of nodule-positive patients. It will both reduce the rate of unnecessary invasive procedures, and on the other hand, will avoid treatment delay when cancer exists. The economic implication of this action is a significant save of ~$12-16 billion for the healthcare system worldwide.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-06-01, End date: 2016-11-30
  • Rcn
    193653
    Nid
    14113
    Project acronym
    MIRAGE 20-15
    Project
    Mid Infra-Red near-field control by Adiabatic frequency Generation Enabling 20fs/15nm resolution
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    The goal of this proposal is to allow observing and controlling ultrafast phenomena in a spatio-temporal window of 20fs-15nm at mid-IR by merging the extreme temporal resolution of the recently developed single-cycle mid-IR pulses with the spatial resolution of near field scattering optical microscope (aSNOM). The mid-infrared wavelength regime is of particular importance to materials science, chemistry, biology and condensed matter physics, as it covers the fundamental vibrational absorption bands of many gaseous molecules and bio-molecules. Adiabatic frequency conversion, a recent advance in nonlinear optics based on my PhD research and my current collaboration with MIT, generates ultrashort pulses in this important wavelength regime, which outperform the currently available mid-IR ultrashort sources, and unlike other techniques allows complete control of the temporal evolution by amplitude and phase manipulation of the NIR input. Combining these capabilities with aSNOM will allow one-of-a-kind route to perform active coherent control of quantum dynamics and allow single shot spatio-temporal observation of fast dynamical processes at nanoscale-resolution. Moreover, mid-IR ultrashort pulses delivered to the nanoscale can produce the high peak power needed to observe the nonlinear properties of the material under examination. Together with the richness of pulse shape manipulation it stands to enable, the currently impossible capability of intra-pulse multidimensional mid-IR spectroscopies at the nanoscale. This will open a gateway to all-optical, non-intrusive and label-free in situ studies of ultrafast processes in 2D materials and topological insulators, peptide evolution, photo-induced surface femtochemistry and protein folding. In particular, I plan to utilize these capabilities to explore nanoscale surface femtochemistry and to study energy pathways of hot carriers following the plasmonic decay in 2D materials and plasmonic nanostructures.
    Max ERC funding
    1,493,250
    Duration
    Start date: 2015-03-01, End date: 2020-02-29
  • Rcn
    197831
    Nid
    14554
    Project acronym
    MetCAF
    Project
    Uncovering the Role of Cancer Associated Fibroblasts in Facilitating Breast Cancer Metastasis
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    Mortality from breast cancer is almost exclusively a result of tumor metastasis. Since advanced metastatic cancers are usually fatal, understanding the biology of tumor metastasis is the most significant challenge in cancer research today. It has become clear that the microenvironment of tumors is crucial in supporting tumor growth. Nevertheless, the role of the metastatic microenvironment in facilitating metastatic colonization is largely unknown. We recently uncovered a novel role for Cancer-Associated Fibroblasts (CAFs) in mediating tumor-promoting inflammation. However, the role of CAFs in the formation of a permissive metastatic niche that enables the growth of disseminated tumor cells is unresolved. I propose to systematically investigate, for the first time, the molecular changes in CAFs that facilitate metastases formation, which may lead to the discovery of novel targets for cancer therapeutics. To achieve this goal, I will integrate tumor biology knowledge and the unique expertise of my lab: we will combine novel mouse models of spontaneous lung metastasis of breast cancer, imitating the clinical setting, with multi-transgenic reporter mice that enable origin tracing and unbiased analysis of fibroblast sub-populations. By performing a comprehensive molecular and functional characterization of fibroblast co-evolution during metastases formation and analysis of breast cancer patient cohorts, we will uncover the dynamic changes in CAFs at the metastatic niche, identify the origin of metastatic CAFs, and elucidate the signaling pathways that govern their functional role in breast cancer metastasis. Molecular understanding of the early stages of tumor metastasis is an essential prerequisite for the discovery of novel therapeutic targets. Achievement of the proposed goals will shed light on a central conundrum in cancer biology and open new horizons for the development of novel therapeutics that will transform cancer into a chronic, yet manageable disease.
    Website (HI)
    Max ERC funding
    1,281,959
    Duration
    Start date: 2015-07-01, End date: 2020-06-30
  • Rcn
    193763
    Nid
    14058
    Project acronym
    MetKnock
    Project
    Precise and non-GMO Engineering of Nutritional Factors for Breeding High Quality Crops
    Host Institution (HI)
    Weizmann Institute Of Science, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    While great attention has been given to increase nutritional substances in food plants only limited efforts have been made for using biotechnology to reduce the level of endogenous, anti-nutritional factors (e.g. toxic compounds) in existing crops. Anti-nutritional substances not only affect the digestion and absorption of nutrients, but can also be lethal to humans or feeding animals and are responsible for food spoilage. Glycoalkaloids (GLAs) produced by crops of the Solanacea family, namely, potato and eggplant, are a major problem for breeders and farmers, as their level must be tightly regulated. Worldwide, between 13 and 27% of the potato crops are discarded because GLA levels are above the maximum currently deemed to be safe. In this PoC project we propose to redesign the potato GLAs metabolic pathway in a precise manner without the insertion of foreign genes, through targeted gene knockouts. Our strategy will be based on the discovery and intellectual property of genes part of the GLAs biosynthetic pathway obtained in the course of the ERC SAMIT project (Aharoni lab; ID-204575) that will be targets for precise, non-GMO metabolic engineering of potato. Know-how from TRACTAR, an ERC project (ID-268646) in the collaborating lab (A. Levy), will serve as the base for generating custom-designed nucleases (i.e. CRISPR/Cas) to be employed for targeted knockouts of potato GLAs genes. We will develop new potato cultivars with low GLAs content and with minimum impact on other plant characteristics, providing a proof-of-concept for potato breeding. In parallel to the technical testing, we will build a strategy to commercialize the IP and prototypes that have been or will be developed in the course of this project. We will identify and contact the relevant partners or investors who have an interest in potato quality and/or in the production of functional health food.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-02-01, End date: 2016-07-31
  • Rcn
    196790
    Nid
    13846
    Project acronym
    MultiScaleNeurovasc
    Project
    Quantifying the structure-function of the neurovascular interface: from micro-circuits to large-scale functional organization
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Starting Grant (StG), ERC-2014-STG
    Summary
    Neuronal computations in the brain require a high metabolic budget yet the brain has extremely limited resources; calling for an on-demand, robust supply system to deliver nutrients to active regions. In most cases, neuronal activity results in an increase in blood flow to the active area, a phenomenon called functional hyperaemia. This coupling between neuronal and vascular activtuy underpins the mechanism enabling fMRI to map neuronal activity based on vascular dynamics; further, malfunction of the cellular players involved in coupling is now considered to play a key role in otherwise classically defined neurodegenerative diseases. We lack a concise description of the inner workings of this mechanism and a thorough quantitative description of the neuro-gila-vascular interface; issues that are best addressed by an investigation into the cellular mechanisms, the temporal dynamics and multi-scale spatial organization governing neurovascular coupling. My long-term goal is to provide a unified theory to encapsulate our knowledge on neurovascular coupling. Here, I hypothesize that functional hyperaemia results from the constant integration of vasoactive cues with region-dependent coupling emerging from different neuro-glia-vascular microcircuits, nuances in afferent wiring into vascular contractile elements and/or neuronal activity patterns. I will test this hypothesis with a multi-faceted correlative approach combining: two-photon awake imaging of cellular and vascular dynamics to obtain physiological data unaffected by anaesthetics; super-resolution structural imaging of intact volumes to map the fine details of micro-circuit structure; array-tomography to map in situ the neurovascular signalling machinery and novel optogenic tools to manipulate several of its specific components. I expect to offer a revolutionary mechanistic insight into one of the most basic and fundamental physiological processes behind the structure and function of the brain.
    Website (HI)
    Max ERC funding
    1,500,000
    Duration
    Start date: 2015-06-01, End date: 2020-05-31
  • Rcn
    198181
    Nid
    14659
    Project acronym
    NEGEVBYZ
    Project
    Crisis on the margins of the Byzantine Empire: A bio-archaeological project on resilience and collapse in early Christian development of the Negev Desert
    Host Institution (HI)
    University Of Haifa, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    This project proposes an innovative, integrative and data-intensive approach to understand the parameters for long-term sustainable functioning of complex societies under vulnerable conditions. The broad aim of the research is to explore contexts of collapse and resilience in an ancient society with high levels of socio-political complexity and technological ingenuity within a resource-limited environment. It focuses on the Byzantine early Christian urban centres of the Negev Desert (4th-7th cent. AD) disclosing both the triumph of human ingenuity in conquering the desert through large-scale human settlement and agricultural development as well as a striking and as yet ambiguous case of wholesale systemic collapse. To test hypotheses regarding social disintegration, economic stress, environmental degradation due to climatic or anthropogenic causes, and the question of plague the project integrates approaches in the archaeology of households, landscapes and garbage through use of biomolecular, botanical, zoological, geological, chronometric, artifactual and contextual sources of data. Dealing with societal vulnerability in marginal regions is timely and relevant in a world where accelerating development rapidly expands such problems, previously localized, to global levels. Although it is a risky endeavour to engage the record of past societies to inform the present and forecast the future due to the typically underdetermined nature of historical and proxy data, this project offers substantial gain to theoretical and empirical research on societal vulnerability in two main avenues: (1) providing an opportunity to critically re-evaluate the current state of knowledge in the field based on an extensive corpus of new, high-quality data and (2) drawing more nuanced and informed broad generalizations regarding limiting states for human ingenuity in reconciling social and economic development with sustainable management of the environment and its resources.
    Website (HI)
    Max ERC funding
    1,445,151
    Duration
    Start date: 2015-09-01, End date: 2020-08-31
  • Rcn
    196345
    Nid
    13921
    Project acronym
    NETEEG
    Project
    Spatial super-resolution of electrophysiological measurements
    Host Institution (HI)
    Tel Aviv University, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    Electroencephalography (EEG) is the non-invasive recording of electrical brain activity, and is an indispensable diagnostic and research tool. A significant advantage of EEG compared to other brain imaging modalities is its high temporal resolution. The downside of EEG is, however, its poor spatial resolution, which is one of the reasons for its gradual replacement by costlier alternatives. It results mainly from the sharp discontinuity in the electric conductivity of the skull bones acting as a strong low-pass filter and limiting the amount meaningful information that can be extracted from EEG signals.   We propose a novel concept of EEG measurement hardware which, in combination with signal processing techniques, will increase the spatial resolution of EEG by as much as an order of magnitude. Our idea is based on the observation that by connecting a dynamic network of controllable impedances between pairs of measurement electrodes, one can alter the shape of the spatial filter constituted by the skull. Since EEG is a relatively narrow-band signal (about 100Hz, limited by the time constants of basics units of neural activity), we expect to be able to measure tens or hundreds of different configurations of the network, either directly or by using a compressed sampling scheme, without compromising the temporal resolution. This will introduce many independent equations to the EEG inverse problem and improve source estimation, having critical impact on the diagnostic capabilities of EEG as well as on its use in emerging applications such as neuro-feedback and brain-computer interface (BCI).
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-04-01, End date: 2016-09-30
  • Rcn
    197092
    Nid
    13755
    Project acronym
    NOVCARBFIX
    Project
    Analysis, Design and Experimental Evolution of Novel Carbon Fixation Pathways
    Host Institution (HI)
    Weizmann Institute Of Science, Israel
    Call details
    Consolidator Grants (CoG), ERC-2014-CoG
    Summary
    Carbon fixation is a prerequisite for accumulating biomass and storing energy in most of the living world. As such, it supplies our food and dominates land and water usage by humanity. In agriculture, where water and nutrients are abundant, the rate of carbon fixation often limits growth rate. Therefore increasing the rate of carbon fixation is of global importance towards agricultural and energetic sustainability. What are the limits on the possible rate of carbon fixation? Attempts to improve RuBisCO, the key enzyme in the Calvin-Benson cycle, have achieved only limited results. My lab focuses on trying to overcome this global challenge by building synthetic pathways for carbon fixation. We create a computational framework that designs and scores pathways and creates step-wise selection strategies for in-vivo experimental implementation. Our most promising synthetic carbon fixation pathways are found to utilize the highly effective carboxylating enzyme, PEP carboxylase. We experimentally test these pathways in the most genetically tractable context by constructing an E.coli strain that depends on atmospheric CO2 fixation. We will gradually incorporate the pathways, initially as essential reaction steps for biomass production, and finally with CO2 as sole carbon input of the cell. As a stepping-stone towards this challenging goal, we will construct an autotrophic E.coli strain that uses the Calvin-Benson cycle. We systematically convert this synthetic biology grand challenge into a gradual evolutionary ladder with independently selectable steps. We recently achieved key steps in the ladder, such as semi-autotrophic growth, serving as powerful proofs of concept. The proposed research will advance our basic-science understanding of evolutionary plasticity of metabolic pathways. It also paves the way for a hybrid rational-design/experimental-evolution approach to revisit and advance the capacity of metabolism for agricultural productivity and renewable energy storage.
    Website (HI)
    Max ERC funding
    1,999,843
    Duration
    Start date: 2016-01-01, End date: 2020-12-31
  • Rcn
  • 196344
    Nid
    13922
    Project acronym
    uDAS
    Project
    An Automatic Microfluidic Device Assembly System
    Host Institution (HI)
    Bar Ilan University, Israel
    Call details
    Proof of Concept (PoC), ERC-2014-PoC
    Summary
    Microfluidic systems, in general, have proven important platforms for biomedical assays. These systems benefit from reduced requirements for expensive reagents, short analysis times, and portability. Although microfluidic systems are convenient platforms, their use in the life sciences is still limited mainly due to the high-level fabrication expertise required for construction.   Integrated microfluidics is one of the most sophisticated three-dimensional (multi layer) solution. It requires soft lithography (PDMS based chips), for production of high complexity microfluidic systems (multiple serial or parallel processes). Integrated microfluidics in particular is almost non-existent in the industry due to the low yield and uncontrolled production process.   My ERC project (MUDLOC-2012) is to develop a microfluidic platform for multidimensional protein array analysis. It uses complex multilayer microfluidic devices that consist of 2 PDMS layers and a glass microarray. The integrated microfluidics system contains thousands of micromechanical valves in micrometer dimensions, controlling thousands of parallel reactions. Our research demands production of hundreds of such devices.   We, as all others who produce integrated microfluidics, suffered from frustrating low yield (15%). In order to improve fabrication yield and to fabricate devices with increased density, we designed and manufactured, a first of its kind, full production process sequence, semi automatic Microfluidic Device Assembly System (µDAS). This resulted in a direct increase of device complexity and yield (85%) over the last half year.   The 2nd generation automated µDAS prototype will become a generic assembly tool for soft lithography. µDAS will enable a critical production standard and process control, which will pave the road for significant penetration of complex integrated microfluidics technology into both academia and industry.
    Website (HI)
    Max ERC funding
    150,000
    Duration
    Start date: 2015-04-01, End date: 2016-09-30
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