Grant Abstracts 2011   Drexel University Alexander Fridman Philadelphia, PA $1,000,000 December 2011 This project will develop a fundamental understanding of bio-molecular interaction pathways between strongly non-equilibrium electrical plasma and living cells.  The work is enabled by recently developed (at Drexel) nanosecond pulsed uniform non-equilibrium plasma (NEP), which makes possible not only the safe application of plasma directly to living tissues, but also accurate plasma characterization.  NEP has been found to produce a variety of important medical and biological effects; however, the mechanisms underlying these effects are not clearly understood.  The major goal of this project is to close the gap in the understanding of NEP characteristics and its effects on biomolecular events in cells.  The project team will study how active species in NEP can be modified through nanosecond control of applied voltage and gasses and determine how these species modulate the effects of NEP on living cells and biomolecules.  To study the effects of NEP on nucleic acids and proteins in solution and in cells, they will utilize biochemical approaches, including mass, Raman, NMR and infrared spectroscopies and small angle X-ray scattering in conjunction with electrical and optical plasma characterization.  Signal transduction pathways affected by NEP treatment of cells will be explored by a combination of biochemical techniques and chemical inhibitors, RNAi and genetically modified cells.   Princeton University Mansour Shayegan Princeton, NJ $1,000,000 December 2011 This is a multidisciplinary effort to obtain the best platform for topological quantum computing.  Such a quantum computer would be millions of times more powerful than the best current supercomputer because, using quantum mechanical phenomena, one could manipulate a vast amount of information with a relatively small number of qubits.  One way of defeating the biggest obstacle, decoherence of qubits, is through the use of topology: the information is encoded in a non-local way so that local defects do not affect the qubits.  Recently, it has been theoretically realized that among the best candidates for such topologically ordered phases are certain exotic states of electrons confined to two dimensions in a magnetic field, called fractional quantum Hall states.  The qubits are the quasi-particle excitations of these states, and their robustness to local decoherence is due to the fact that they might obey the so-called non Abelian statistics which describe how the system changes when exchanging indistinguishable excitations.  These states, however, are extremely fragile and their statistics are not known.  The solution to obtaining a viable topological quantum computing platform lies in a concerted effort that combines powerful experimental and engineering techniques with advanced theoretical physics and numerical simulations that will push the boundaries of today’s computing techniques.   University of California, Berkeley Rosemary Gillespie, Charles Marshall Berkeley, CA $1,500,000 December 2011 The next generation of predictive models of the biotic response to environmental change must meet the challenge of incorporating the effects of complex interactions among organisms, climate, and their physical and biotic environments.  A great variety of data types are required to meet this challenge, including current and past species’ distributions, the increasing amount of associated data on their genotypes and phenotypes, and how these have changed in space and time, as well as empirical and modeled data on environmental and climate change.  The goal of this project is to develop a Predictive Biosystems Informatics Engine (PBIE), the informatics infrastructure needed to access, visualize, and analyze these rich data sets, thus providing the foundation for building the next generation of models of the biotic response to global change.  The unique combination of data in Berkeley’s Natural History Museums, Field Stations, and faculty labs, the University’s expertise in bioinformatics and the digitizing and serving of organismal and environmental data, and a world-class community of scholars and students make the unprecedented scale and complexity of the proposed effort possible.  The PBIE will innovate with cutting-edge technologies, and once operational, will enable cross disciplinary exploration of the vast and disparate data sources required to understand biotic response to global change.   University of California, San Diego Jules S. Jaffe La Jolla, CA $1,000,000 December 2011 Approximately one third of the oxygen we breathe is generated through the photosynthesis of marine organisms discovered only in the last 30 years.  These organisms form the base of all marine food webs and are important in regulating the planet’s climate, yet almost everything known about them comes from bulk samples or laboratory experiments.  Their small size presents challenges that have made direct observation in the ocean using existing technology difficult, if not impossible.  A team at UCSD proposes to build the world’s first high resolution, 3D, in situ, underwater microscope.  The microscope will be configured with an inner imaging volume with high spatial resolution nested inside a larger, lower-resolution imaging volume.  Image analysis of data from the high-resolution inner volume will permit identification of marine nanoplankton, while analyses of the larger, outer volume will permit subsequent tracking and behavioral observations.  The microscope will also simultaneously image fluorescence to enable discrimination between zooplankton and different kinds of phytoplankton that are important in global carbon cycling.  The new device and its subsequent use will allow seeing, for the first time, the most abundant organisms on the planet in situ and how they interact with each other.   University of Chicago Gregory S. Engel, David A. Mazziotti, Dmitri V. Talapin Chicago, IL $1,000,000 December 2011 Designing and synthesizing materials for efficient transfer of energy and information presents a grand challenge for modern science.  The notion of the chemical bond, developed in the early 20th century from the principles of quantum theory, revolutionized the ability to predict static and dynamic properties of molecules.  A team at the University of Chicago proposes to create a theoretical framework for synthesizing and assembling nanostructures with control of structure and function to yield materials with predictable properties and functions for the efficient transfer of energy and information.  The concepts of “atoms” and “bonding” can be generalized to enable the construction of functional materials from fundamental units of nanostructures – which they call “designer atoms.”  The team proposes to develop and rigorously test systematic rules, based on the principles of quantum mechanics, for assembling (or bonding) “designer atoms” into materials with a broad array of properties and functions.  Guided by recent research and using novel experimental and computational techniques, they will investigate the strong entanglement of electrons, emerging from subtle forces between nanostructures, to elucidate these fundamental principles and to design new materials.  If successful, the project may provide a new paradigm akin to the chemical bond to enable advances in chemistry, physics and materials research.   Woods Hole Oceanographic Institution Jeffrey J. McGuire and John Collins Woods Hole, MA $1,000,000 December 2011 The Cascadia subduction zone offshore of Northern California, Oregon, Washington and British Columbia had its last major earthquake and tsunami over 300 years ago and has been building up strain for the next earthquake since then.  The majority of this fault, which could produce a Magnitude 9 earthquake at any moment, lies offshore, where there are currently no geodetic instruments set up for monitoring the buildup of strain.  Hence, scientists have relatively little ability to project the details of the next earthquake.  The project will install the first seafloor geodetic observatory above the locked, offshore portion of the Cascadia fault.  It will also mount state-of-the art geodetic instruments (tiltmeters) in an existing borehole offshore of Vancouver Island that will have real-time data availability through the NEPTUNE cabled observatory and will be co-located with already existing sub-seafloor hydrological monitoring equipment.  Together these instruments will enable new interdisciplinary studies of the fluid flow transients within the subduction system.  Additionally, a wider array of instruments for measuring the vertical deformation of the seafloor both at short and long time scales will be installed.  These pressure gauge benchmarks will allow a determination of whether the Cascadia fault is locked to shallow depths, and hence likely to rupture in a manner similar to the recent catastrophic Japanese earthquake.   Arizona State University Nongjian Tao Tempe, AZ $1,000,000 June 2011 This project aims at developing a technology to measure one of the most fundamental and important quantities in nature, the mass of a single molecule.  The research question to be addressed is “How can we precisely measure the mass of a single molecule, identify the molecule based on its mass, and study its affinity properties without using labels?”  Unlike conventional microfabricated mechanical oscillators, this project proposes a self-assembled molecular oscillator approach.  The success of the project may lead to unprecedented capabilities for studying single molecules, allowing the limitations of the current mass spectroscopy and immunoassay technologies to be overcome and providing a detection technology to cover the “Terahertz gap” in the electromagnetic spectrum.  The research team at the Biodesign Institute at Arizona State University is dedicated to the study, control and detection of single molecules, the smallest building blocks of functional devices, and to transform these capabilities into functional devices for solving real-world problems.  The team has pioneered techniques to create and study single molecule junctions, and developed a plasmonic imaging technique for measuring nanoparticle surface interactions, which have prepared them to achieve the goals of this project.   Boise State University William L. Hughes Boise, ID $1,000,000 June 2011 The vision is to fundamentally change early-stage disease diagnosis and treatment on a global scale.  Using engineered biochemical tools, the team integrates biology with physics, chemistry, materials science and computer science to pioneer a novel disease detection system.  The goal is to detect disease via DNA reaction networks that report the presence of disease-specific micro-RNAs (miRNAs) found in human blood.  To offer flexibility and scalability, the approach uses modular reaction networks that consist of a translator, cross-catalytic amplifier and reporter.  The translator module accepts a target miRNA as an input signal and outputs a specific DNA sequence, which then acts as the input into the amplifier module.  The multiplied output of the amplifier module drives the reporter module.  The reporter module generates a colorimetric change in vitro based on relative miRNA concentrations signifying a positive/negative signal for disease, analogous to the results of a disposable pregnancy test.  Alternatively, when operated in vivo, an additional feedback module may prevent disease onset and progression.  As miRNAs are linked to over 270 diseases, this concept is broadly applicable to human health.  If successful, this diagnostic tool may reduce mortality through early screening, even where medical equipment and resources are scarce.   Northwestern University Mark C. Hersam Evanston, IL $1,000,000 June 2011 Graphene, a one-atom-thick planar sheet of carbon atoms in a honeycomb lattice, has attracted substantial attention for its superlative electronic, thermal and mechanical properties.  A wide range of transformative applications, including electronic devices, sensors and composite materials, have been anticipated for graphene.  Graphene’s seemingly limitless potential was recently recognized with the 2010 Nobel Prize in Physics.  However, as has been shown in other materials systems, graphene’s potential could be dramatically enhanced by creating chemically modified variants of the parent material.  The team at Northwestern seeks to explore inorganic and organic chemical functionalization of graphene with the goal of establishing new classes of two-dimensional nanomaterials with tailored chemical, electrical and optical properties.  Rather than optimizing properties empirically, the approach will be to employ ultrahigh vacuum scanning tunneling microscopy to characterize and understand chemically modified graphene at the atomic scale.  These detailed studies will develop fundamental principles that will guide future efforts to exploit novel graphene-derived nanomaterials in numerous societally pervasive applications, such as information technology, biotechnology and renewable energy.   University of California, Davis Gang-yu Liu, Ian Kennedy Davis, CA $1,000,000 June 2011 Establishing the “structure–mechanical property–function” paradigm at the single cell level is of critical importance in understanding individual and collective behaviors such as wound healing, tissue engineering, and cancer diagnosis and therapy.  Current advances have revealed a strong correlation within the paradigm.  This project will develop a simple and reliable method to enable exploration of the paradigm systematically and quantitatively.  Based on combined atomic force and laser scanning confocal microscopy, the new method develops specifically modified probes and accurate mechanical positioning to conduct high-resolution imaging and cellular mechanics of living cells in vitro.  The micro-mechanical measurements will be acquired at length and time scales relevant to cell function, and processed with custom written code to quantify mechanics such as Young’s moduli.  This approach will first be used to uncover the sub-cellular mechanism associated with the inflammatory responses of human aortic endothelial cells and lung macrophages following exposure to manufactured nanomaterials.  The outcome shall demonstrate that assessment of health risk is complex and multimodal, and that this paradigm at the single cell level provides a complementary and possibly more sensitive means for risk assessment.  Upon development, this technology will be made available in the W. M. Keck Spectral Imaging Facility to all researchers.   University of California, Los Angeles Andrea Ghez Los Angeles, CA $1,000,000 June 2011 This project will develop a new methodology that will enable ground-breaking tests of Einstein’s theory of General Relativity (GR) and black hole growth models never before possible.  Such cutting-edge tests are within reach, using the telescopes at the W. M. Keck Observatory equipped with Adaptive Optics (AO), a revolutionary technology that has begun to allow astronomers to overcome the blurring effects of Earth’s atmosphere.  While the AO system has dramatically upgraded our ability to see into space, it has not reached its full scientific potential.  Measurement precision from Keck AO observations is limited by lack of knowledge of how the atmosphere has affected each point in the image.  This kind of data is finally publicly available through new equipment that provides measurements of turbulence at multiple layers in the atmosphere.  The UCLA team proposes to develop a new methodology (AO-Optimization) for using this data in post-processing to dramatically improve AO measurement precision across the entire field of view.  It is imperative to begin this work now so that the Keck AO system can be optimized in time to detect the effects of GR that will be possible to measure from observations of the nearest star ever imaged around a supermassive black hole (SO-2), as it makes its closest approach with the black hole, between 2016-2020.  There will not be a comparable event to test GR until 2034.   University of California, Santa Cruz Joel Kubby, William Sullivan, Yi Zuo, Don Gavel, Scot Olivier Santa Cruz, CA $1,000,000 June 2011 This project will establish an Adaptive Optical (AO) Microscopy Center to develop enabling technologies and critical procedures to overcome long-standing barriers and vastly improve deep tissue biological imaging.  The approach is inspired by the highly successful use of AO in the W. M. Keck Telescopes, which allows astronomers to see much more clearly and deeply into space.  Members of the team have been at the forefront of these innovations in astronomy and are now working with biologists to apply the same principles to overcome similar barriers that inhibit deep-tissue light microscopy.  A critical aspect of the method involves direct wavefront sensing of biological “guide-stars,” coupled with the use of deformable mirrors, to adjust the optical system to correct for optical distortions that occur as light passes through the inhomogeneous specimen.  The team will create these guide-stars using genetically modified, fluorescently tagged proteins and develop the AO two-photon optical and sensing systems needed to take advantage of them, then test this technology in a mouse model system.  This project may enable dramatic improvements in imaging of the cellular universe, enabling biologists to examine crucial living processes deep within tissues and organs at a scale previously impossible, and lead to new biomedical interventions, such as stem cell therapies.