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Transformative Science
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The BSF began its Transformative Science grants program in 2010.



Time Domain Astrophysics: Enabling the Revolution

Prof. Avishay Gal-Yam, Weizmann Institute of Science
Dr. Eran Ofek, Weizmann Institute of Science

Dr. Peter Nugent, Lawrence Berkeley National Laboratory


One major goal of modern astronomy is to unveil new and perhaps completely unimagined phenomena from the vast amounts of experimental data that is collected. Ongoing sky surveys show that currently, only a small fraction of the data is being used, and that exploration of such datasets is limited by data analysis tools and algorithms rather than by researchers' imaginations. The researchers propose to develop a new generation of image addition and subtraction algorithms, methodologies and codes that will be used to analyze data from near-future surveys that will increase the survey speed and solve many of the critical problems that the field is currently facing. Particular emphasis will be placed on the analysis of transient images, which currently suffers from false positives that must be 'hand tuned'. The algorithms proposed will allow automatic transient detection and preliminary results have been presented. This may enable the analysis of the faint first light escaping from an exploding star, just as the explosion goes off. Imaging the transient at high time resolution will allow for deeper understanding of the entire process. In contrast to many transformative proposals, this project is focused on a methodology and not a specific scientific question. However, the potential advances and the fact that the scientists plan to publish their work in open-access venues and make their codes freely available, may leverage these advances to impact other fields where transient imaging is important, such as quantitative biology, medical sciences, material sciences, and environmental sensing.




Architecture and Stability of Non-Membranated Organelles Investigated by Novel Cryo-Electron Tomography


Prof. Michael Elbaum, Weizmann Institute of Science

Prof. Clifford Brangwynne, Princeton University


The proposed transformative project will provide unique structural information on the unique phenomena of non-membranated organelles in cells, including nucleoli, Cajal bodies, P-bodies, and stress granules. Understanding the structural organization of these molecular entities requires new concepts and measurements that apply physical approaches to cell biology. While traditionally it was assumed that compartmentalization requires a lipid membrane to define the boundary between inside and out, these cellular compartments lack a surrounding membrane. Instead, their self-assembly is due to molecular interactions among the components and little is understood about the ultrastructure, self-assembly mechanism and dynamics of these organelles. The process of compartmentalization is also important from the biophysical point of view since the thermodynamic mechanism of self-organization into these stable structures and the observed size selection is still unknown, and its study may be important for the investigation of other self-association processes. The method of choice for the characterization will be cryo-scanning transmission electron microscopy tomography, a unique experimental approach, as this is the only method that can provide direct and detailed information about this system, since conventional electron microscopy is too invasive while traditional cryo-microscopy is restricted to very thin specimens. Light microscopy, even with super-resolution methods, cannot resolve the relevant structures that characterize these systems. The US team, a pioneer in the field of non-membranated organelles, will provide the purified structures to be studied by the Israeli team, which has world-leading expertise in cryo-scanning transmission electron microscopy tomography. This research is likely to lead to a true advance in cell biology.



Functional Characterization of Circular RNAs in Individual Neuronal Populations

Dr. Sebastian Kadener, Hebrew University of Jerusalem

Prof. Justin Blau, New York University


CircRNAs are an exciting, newly-discovered type of RNA which as the name suggests are circular products of RNA splicing.  Neurons have been shown to have abundant circRNAs, and this proposal seeks to determine the role of circRNAs in neuronal function, focusing on neurons involved in circadian control in Drosophila. To examine the role of circRNAs, the proposal fuses state of the art techniques applied to a well characterized biological system, circadian biology. A distinct strength of the proposal is the focus on the Drosophila s-LNv (small lateral ventral neuron) population to sequence, since these cells have clear morphological, physiological and behavioral outputs that can be interrogated to determine functionality of the circular RNAs that will be identified. As one of the reviewers wrote, “this smart choice of cells and creative sequencing techniques should yield a first view into this surprising new world of circular RNAs and should begin to reveal why these RNAs are present at such high levels in neurons and what they are doing there”.  The project will characterize circRNAs in the LNvs and then will manipulate their expression and conduct behavioral and cellular assays that measure s-LNv function. In addition to the discoveries they will make regarding circRNAs, if the research team develops procedures to characterize non-polyadenylated RNA from small numbers or individual neurons, those procedures would also be transformative for the neuroscience field as well as other areas in biology.




Active Control of Light Propagation and Focusing through Stong Scattering Media


Prof. Nir Davidson, Weizmann Institute of Science

Prof. Hui Cao, Yale University


Light transport in complex disordered media is a fundamental physical phenomenon, and it is significant in numerous applications including imaging through turbid layers, and in biomedical applications. At the interface between two media with different refractive indices, light refraction and reflection occur; when the interfaces become numerous and complicated such as in biological tissue, multiple light scattering events occur and this scrambles light paths in extremely disordered ways, which cause the objects behind or inside the scattering media to become opaque primarily due to such multiple light scattering and not absorption. The main challenge therefore is to control the many degrees of freedom of the optical wave front. Such control is usually achieved by wave front shaping of the   incoming beam using a spatial light modulator (SLM), and applying iterative algorithms and active electronic feedback loops. However, SLM-based wave front shaping is limited to long acquisition times and is relatively slow and has shown limited success.  In the present proposal a new approach is suggested for wave front shaping, based on passive all-optical negative feedback. In this method the many modes of the complex field compete over the same optical gain, and thus reach a desired steady state solution based on the form of feedback. By tailoring the feedback, the authors propose to fully control propagation of light in the random media, and generate total transmission, absorption, focusing and imaging. This has the clear advantages of simplicity and speed, and is expected to dramatically improve the ability to control light propagation in random media. They intend to study the basic physical principles of negative feedback in such systems, and to examine different methods of applying negative feedback to control light propagation in ways that are not currently feasible, such as full transmission in thin and thick random media, focusing and imaging. It is clear that impact of this research is important in the field of optical science. If the project is successful in making the expected proof of concept, then the method should be directly applicable in several domains including the development in a biomedical context where the evolution of e.g. living tissues can be followed with an excellent temporal resolution. Imaging deep in biological tissue is one of the greatest challenges facing the optical imaging community. It will allow for 3D imaging of biological tissue in-vivo, or at least, in thick ex-vivo samples. This will thus allow for functional and structural imaging of tissue in its most realistic, native state, something which is not currently available.





Multimodal Whole Mammal Physiological Analysis

Dr. Pablo Blinder, Tel Aviv University

Prof. Ed Boyden, Massachusetts Institute of Technology


This work aims at making the relatively small Etruscan Shrew, which is closer to primates than the laboratory mouse, into a novel model for brain imaging of blood circulation as a tool for assessing brain functioning coupled with advanced molecular genetics. It was defined by the ad hock reviewers and evaluation panel as an ambitious and truly transformative plan and they emphasized its innovative nature. Life Sciences research is highly dependent on and affected by the animal model systems that are available for experimentation; adding one more animal model to the research repertoire can make a real revolution by offering both imaging modalities and the capacity for applying state of the art molecular genetics tools that would be relevant to humans. Tree shrews notably show stress responses that are close to human reactions, supporting the wisdom in this selection beyond the size alone. The main risk is if the neuroscience community will accept this new model, such that this high risk - high gain application fits the foundation's goals.




Unique Surface Transfer Doped Diamond: Unusual Physics and Realization of Superior Electronic Devices


Prof. Rafi Kalish, Technion - Israel Institute of Technology

Prof. Jesus Del Alamo, Massachusetts Institute of Technology


Diamond is a material with excellent electrical and thermal properties. A novel approach opens the possibility to transform diamond into a next generation semiconductor material. The new approach is doping in an innovative manner to produce n type and p type regions needed for semiconductor operation. The approach is to use a surface layer of Mo03 as an electron acceptor which then creates a subsurface hole layer on the hydrogen terminated diamond. This created a 2D excitonic layer of electrons opposite holes, perhaps with protected topological properties. This holds the promise of new physics and unprecedented high power and high frequency devices. The physics can allow for relativistic Dirac gapless electronic states. The transformative aspects of the research is the possibility to design, fabricate and produce the next generation beyond Si and Ge semiconductors with an exceptional order of magnitude improvement in electrical and thermal properties.





Topological Photonics

Prof. Mordechai Segev, Technion - Israel Institute of Technology

Prof. Marin Soljacic, Massachusetts Institute of Technology


The study of topological insulators has been one of the hottest topics in solid state physics for the past few years.  Topological insulators are materials in which electronic current flows along the surface while the bulk is insulating.  Special quantum mechanical properties make the electronic surface states topologically protected, enabling coherent flow with no scattering and loss.

The present proposal is transformative in the sense that it is proposed to study analogous effects in photonic systems. Such photonic topological insulators will enable the study of fundamental issues in topologically protected photonic states such as the effect of disorder, field enhancement effects and topological slow light devices. The analogy between photonic phenomena (in these optical systems) and electronic phenomena in solid state systems is of fundamental importance. Moreover, it is expected that the photonic systems will be much more accessible to detailed analysis. The research is also promising for a great variety of practical applications in quantum computing and communication as well as for integrated optical circuits and energy efficient devices.




Gene-Virus Interactions in Kidney Desease


Dr. Barry Freedman, Wake Forest University

Prof. Karl Skorecki, Technion - Israel Institute of Technology


This proposal introduces an important new concept with enormous scientific and public health implications, that a gene variant associated with high risk of disease confers this risk because it predisposes to an unknown chronic viral infection. In this case, the APOL1 variant, which is associated with a markedly increased risk of chronic kidney disease among African Americans, is hypothesized to predispose to increased risk of an unknown viral infection. The investigators will seek this candidate virus using state of the art deep sequencing of DNA and RNA of affected individuals who have the variant and chronic kidney disease, compared to patients with chronic kidney disease who do not have the APOL1 risk variant. If candidate viruses are discovered, a cause-effect relationship will be validated by establishign novel animal models. The reviewers are uniformly enthusiastic about the quality of the proposal, the state of the art methods proposed, and the potential impact beyond kidney disease. Although some related work has been done in HIV related kidney disease in African Americans, and in resistance to interferon in HCV infections, no prior studies have ever proposed so comprehenseive and compelling an approach. With improved methods for high throughput screening increasingly available, this approach could be applied very widely to many diseases where a gene variant confers a risk of disease without a clear explanation. 




Utilization of Few-Body Control to Stabilize the Unitary Bose Gas

Dr. Lev Khaykovich, Bar Ilan University

Prof. Chris Greene, Purdue University


The proposal suggests studying a new quantum coherent state of matter composed of strongly interacting Bose gases. This phase has not been created before because of stability difficulties due to inelastic three body interactions and collapse into bound states. The ideas proposed by the authors are original and innovative. If successful, it will have a transformative impact on the field Bose gases. It is likely to also have an impact on theoretical work on quantum many body systems far removed from the Bose gases. The proposal is well written and logical, creative and inventive. The strength of this proposal is that the investigators have identified a problem of fundamental theoretical interest, and have proposed a creative and original approach to attack it.


Drift-Mediated Biogenic Mixing in the Ocean

Prof. Alexander Leshansky, Technion - Israel Institute of Technology
Prof. John Dabiri, California Institute of Technology


"The Greenest Energy": Coupling Electron Transfer from a Biological Photosynthetic System to Hydrogen Production

Prof. Noam Adir, Technion - Israel Institute of Technology
Prof. Gadi Schuster, Technion - Israel Institute of Technology
Dr. Avner Rothschild, Technion - Israel Institute of Technology
Prof. Harry Gray, California Institute of Technology


Enabling New Radio Architectures and Network Protocols by Breaking the Nyquist Barrier

Prof. Yonina Eldar, Technion - Israel Institute of Technology
Prof. Andrea Goldsmith, Stanford University


Regulation of Alternative Splicing by Small Non-Coding RNAs

Prof. Ruth Sperling, Hebrew University of Jerusalem
Prof. Stefan Stamm, University of Kentucky


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