RISE Past Awardees

2017 Awardees

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Columbia University Fortifies Research Collaborations with Distinguished Funding Competition

RISE competition identifies six teams to receive funding for innovative research collaborations.

Columbia University Office of the Executive Vice President for Research announced today the names of six teams receiving funding through Research Initiatives in Science and Engineering (RISE), one of the largest internal research grant competitions within the University. The annual award provides funds for up to six interdisciplinary faculty teams from the basic sciences, engineering, and/or medicine to pursue blossoming and extremely creative research projects. Each team’s award is worth $80,000 per year for up to two years.

The RISE competition was created in 2004 to provide Columbia faculty and research scientists with the initial funding necessary to explore paradigm-shifting and high-risk ideas. Amidst federal budget cuts for the sciences, researchers are increasingly challenged to provide more conclusive initial proofs of concept to demonstrate viability, even though they lack funding to complete such preliminary work. In this competition, Columbia follows the National Institutes of Health’s definition of high-risk research as having “an inherent high degree of uncertainty, and the capability to produce a major impact on important problems.”

RISE serves two fundamental purposes: Firstly, it seeds imaginative and daring interdisciplinary research collaborations,” says G. Michael Purdy, Executive Vice President for Research, and Professor of Earth and Environmental Sciences. “Secondly, it strengthens these projects chances of receiving future federal funding in a mutable climate. RISE will empower these six new teams, just as it has done for the 61 previous awarded teams. RISE’s investment can be quantified–funded projects have received back 600% of the original investment in follow-on funding from the government and foundations, which testifies to the distinction of our researchers and the great utility of seed funding at Columbia. With the impending cuts to federal discretionary spending, seed funding programs such as RISE have never been more important.”

The 2017 competition accepted 29 Round 1 applications, thereafter inviting 10 full proposals into Round 2. Between six and nine reviewers were assigned to each Round 2 proposal in order to evaluate the interdisciplinary quality, potential impact, and innovation of each project. 94 reviewers—tenured or tenure-track faculty or research scientists within the University—participated in selecting this year’s awarded teams.

“It is never easy to select only five or six projects from so many extraordinary proposals,” says Victoria Hamilton, Executive Director of Research Initiatives, and administrator of RISE. “This year alone, 94 reviewers generously lent expertise to select the high-risk, high-reward proposals that RISE seeks to seed. Some of these six projects–-just like some of the previously awarded projects–-may not result in the substantial discovery and impacts that they targeted, but this is the hallmark of risky research. We are excited by each of the teams and their proposed challenges, and eagerly await the inevitably remarkable discoveries that these investigations will make over the coming years.”

2017 RISE AWARDEES

Integrating Information Sampling and Decision Making Through Large Scale Testing of Human Information Seeking Behavior
Jacqueline Gottlieb, Associate Professor, Department of Neuroscience
Michael Woodford, John Bates Clark Professor of Political Economy, Department of Economics

Understanding information sampling decisions—our ability to seek information from specific sources at specific times—is crucial for describing phenomena of central interest in economics, neuroscience, and psychology. However, our field has scant empirical evidence that characterizes such decisions and can constrain formal theories. The experiments we propose are motivated by preliminary data we obtained indicating that human information sampling policies show marked individual variation and contradict the predictions of normative models. We propose to extend these results by developing novel APPs that are downloadable on mobile devices, and allow collection of much larger data sets than is possible with standard methods (20,000 participants or more). In parallel, we will extend prominent economic theories of information sampling in ways that are consistent with the empirical data. Together, our efforts will (1) provide empirical answers to key questions regarding information sampling policies; (2) allow significant extension of normative theories of decision making to take account of informational constraints and the strategies that individuals use to overcome these constraints; and (3) establish a robust behavioral testing platform that can be extended in the future to gather other types of “big data” on human behavior.

APTAPAINT: Towards Single-Molecule Glycan Sequencing
Henry Hess, Professor, Department of Biomedical Engineering
Milan Stojanovic, Associate Professor of Medical Sciences, Departments of Medicine and Biomedical Engineering
Sergei Rudchenko, Adjunct Assistant Professor, Department of Medicine

We pursue a super-resolution microscopy approach named APTAPAINT that maps substructures on individual sugar molecules using engineered oligonucleotide-based receptors (aptamers). APTAPAINT will be used in a wide array of applications, from precise assessment of binding kinetics, to epitope mapping, structure reconstruction and heterogeneity studies. As a result of our experiments and the introduction of advanced imaging and signal processing approaches, we will enable commonly available and low-cost microscopes as broadly applicable tools in studies of complex sugars. We will additionally pursue the potentially transformational ability to sequence individual oligosaccharide molecules.

A Novel Spectrometer for Discovering Signals from the Beginning of the Universe
Bradley Johnson, Assistant Professor, Department of Physics
Harish Krishnaswamy, Associate Professor, Department of Electrical Engineering

The cosmic microwave background (CMB) is a bath of photons that fills the entire Universe, and carries critical information about how the Universe began. CMB observations to date have helped reveal that the Universe is 13.8 billion years old, space-time is flat, and the energy content of the Universe is primarily composed of mysterious dark matter and dark energy. The field of CMB research is now searching for exciting and extremely faint new signals embedded in the CMB that appear today as spectral distortions. In particular, a recombination line signal should have been produced when hydrogen and helium nuclei captured electrons when the Universe existed as a structure-less primordial plasma. These emission lines must exist if our understanding of the early Universe is correct, so a recombination line experiment will serve as a unique and powerful test of the current cosmological model. Further, a precise characterization of this spectrum will yield information about the relative abundances of hydrogen and helium in the Universe when it was approximately 380,000 years old, because these two nuclei produce unique features in the spectrum. One feature-rich section of the recombination line spectrum lies between 3.5 and 8.5 GHz, and our ultimate goal is to be the first to discover the recombination line signal by making spectroscopic measurements in this spectral band. The anticipated signal is extremely faint and therefore challenging to detect. Forecast calculations show that an array of thousands of cryogenically-cooled antenna systems will ultimately be needed to detect the cosmological signal. Therefore, a piecemeal approach that starts with the rigorous study of a single prototype antenna is appropriate. With RISE support, we will leverage exciting and ongoing R&D work in the field of silicon RF electronics for commercial wireless communication applications and develop a scalable spectrometer array element that will serve as a stepping-stone to a large array in the future.

Predicting Volcanic Eruptions Using Real-time 4D+ Microscopy of Bubble Interactions in a Solid-Liquid Mush
Einat Lev, Lamont Assistant Research Professor, Division of Seismology, Geology and Tectonophysics, Lamont-Doherty Earth Observatory
Elizabeth Hillman, Professor, Departments of Biomedical Engineering and Radiology

Magma, the driver of volcanic eruptions, is a three-phase mixture composed of liquid melt, solid crystals, and gas bubbles. The interaction between these three components determines the style of eruption: a violent explosion, a moderately energetic lava fountain, or a quietly oozing flow. Scientists studying volcanoes have developed theories to describe how particles or bubbles move within a viscous liquid, yet models for the behavior of all three phases together are still lacking. Lab experiments using three-phase mixtures have so far been limited in their ability to directly observe these interactions–experiments have observed flow from the outside of the flow chamber, flows have been limited to only narrow, two-dimensional domains, or three-dimensional images have been made only after flow and interactions have ceased. We will be using a novel microscopy technique (SCAPE) to image, for the first time, the interaction of particles and bubbles suspended in a viscous liquid, in three dimensions and in real time. Our observations will provide constraints to models of three-phase flow and insight into magma dynamics and volcanic eruptions.

Brain Functional Imaging with Simultaneous fMRI and Doppler Ultrasound
Qolamreza Razlighi, Assistant Professor of Neuroimaging, Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain
Elisa Konofagou, Robert and Margaret Hariri Professor, Departments of Biomedical Engineering and Radiology
Ken Shepard, Lau Family Professor, Departments of Electrical Engineering and Biomedical Engineering

We propose a novel, non-invasive, whole-brain, and in vivo functional imaging method, which has the potential to provide a significantly more direct measurement of brain neuronal activity than is currently possible with BOLD fMRI alone. This method combines traditional fMRI with simultaneous real-time 4D ultrafast ultrasound Doppler imaging. The acquired imaging data will go through a set of post-processing reconstructions to generate brain functional images that measure CMRO2 at resolutions better than that achieved in BOLD signal. This functional imaging method is expected to have widespread impact on neuroscience research, providing a significant step forward in investigating neurodegenerative diseases such as Alzheimer.

Visualizing Ion Transport in Battery Electrolyte by Stimulated Raman Scattering Microscopy
Yuan Yang, Assistant Professor, Department of Applied Physics and Applied Mathematics
Wei Min, Associate Professor, Department of Chemistry

High-performance rechargeable batteries are indispensable to a broad range of applications, including electric vehicles and grid-level energy storage. Transport of ions in battery electrolyte and their insertion into solid electrodes are critical to battery performance. For example, inhomogeneity of ion flux in the electrolyte can deplete ions locally, which not only reduces energy/power density, but also deteriorates cycling life. Therefore, visualizing and quantifying ion transport in the electrolyte and at the solid-liquid interface will not only provide better understanding of battery processes, but also help design better electrolytes and electrodes to enhance battery performance and safety. Here we propose to use the emerging Stimulated Raman Scattering (SRS) microscopy to realize such 3D imaging of ion transport in the battery electrolyte. SRS microscopy is label-free, and its dual-beam configuration employs the stimulated emission amplification, gaining 100 million times higher sensitivity than the common spontaneous Raman microscopy, which enables fast imaging at second level to resolve the transport dynamics of battery electrolyte. Such studies will deepen our understanding of battery reactions and guide further development of batteries with high performance

PROGRAMMATIC IMPACT

"My new project with Brad Johnson will develop a novel technology that will yield great insights into how the universe was created, by detecting minute cosmic distortions due to the recombination of hydrogen and helium in the early universe,” says Harish Krishnaswamy, Associate Professor in the Department of Electrical Engineering, and 2017 RISE awardee. “Detecting these extremely weak signals requires building a radio receiver that can essentially find a needle in a haystack, requiring thousands of highly-sensitive antennas that can operate in the presence of extremely large interference signals. We believe that utilizing these emerging technologies from the telecommunications field can provide compelling insights into the history of the cosmos. While too wild for conventional federal funding, we believe that RISE program will better position us at launching this instrument into space, and will open up new opportunities for reimagining cosmic history and evolution."

RISE not only awards critical seed funding for risky and interdisciplinary collaborations; once the funding has ceased, it tracks how the seed funding contributes to the researchers’ abilities to obtain subsequent sponsorship from government agencies and private foundations.

“It is critical for research institutions to provide internal funding in support of interdisciplinary research, especially as we see external funding budgets wax and wane,” says Christine Denny, Assistant Professor in the Department of Psychiatry, and 2016 RISE Awardee. “For my project with Michal Lipson, we are developing a novel technology for both visualizing and manipulating memory traces in the entire mouse brain while not disrupting surrounding tissue – this could have a great influence on future studies in neurology and psychiatry, but federal funders would not sponsor this research without a proof of concept. RISE has given us the time and funds necessary to develop this proof of concept, and soon we will put it to the test. Had we not received RISE sponsorship, this investigation may never have happened.”

Since 2004, RISE has awarded $9.22 million to 67 projects. These 67 teams later secured more than $55.4 million from governments and private foundations: a 600% return on Columbia’s initial investment. These projects have additionally garnered more than 130 peer-reviewed publications and educated more than 130 postdoctoral scholars and graduate, undergraduate, and high school students.

Nominations for the 2018 competition will run from September to early-October 2017, with five to six awarded teams announced by spring 2018.

For interview requests and additional information, or to partially- or fully-fund a new RISE project, contact Marley Bauce (marley.bauce@columbia.edu; 212-854-7836).

Jacqueline Gottlieb, Michael Woodford

Understanding information sampling decisions—our ability to seek information from specific sources at specific times—is crucial for describing phenomena of central interest in economics, neuroscience, and psychology. However, our field has scant empirical evidence that characterizes such decisions and can constrain formal theories. The experiments we propose are motivated by preliminary data we obtained indicating that human information sampling policies show marked individual variation and contradict the predictions of normative models. We propose to extend these results by developing novel APPs that are downloadable on mobile devices, and allow collection of much larger data sets than is possible with standard methods (20,000 participants or more). In parallel, we will extend prominent economic theories of information sampling in ways that are consistent with the empirical data. Together, our efforts will (1) provide empirical answers to key questions regarding information sampling policies; (2) allow significant extension of normative theories of decision making to take account of informational constraints and the strategies that individuals use to overcome these constraints; and (3) establish a robust behavioral testing platform that can be extended in the future to gather other types of “big data” on human behavior.

Henry Hess, Milan Stojanovic, Sergei Rudchenko

In this proposal, we pursue a super-resolution microscopy approach named APTAPAINT that maps substructures on individual sugar molecules using engineered oligonucleotide-based receptors (aptamers). APTAPAINT will be used in a wide array of applications from precise assessment of binding kinetics, to epitope mapping, structure reconstruction and heterogeneity studies. As a result of our experiments and introduction of advanced imaging and signal processing approaches, we will enable commonly available and low cost microscopes as broadly applicable tools in studies of complex sugars. We will also pursue the potentially transformational ability to sequence individual oligosaccharide molecules.

Bradley Johnson, Harish Krishnaswamy

The cosmic microwave background (CMB) is a bath of photons that fills the entire Universe, and carries critical information about how the Universe began. CMB observations to date have helped reveal that the Universe is 13.8 billion years old, space-time is flat, and the energy content of the Universe is primarily composed of mysterious dark matter and dark energy. The field of CMB research is now searching for exciting and extremely faint new signals embedded in the CMB that appear today as spectral distortions. In particular, a recombination line signal should have been produced when hydrogen and helium nuclei captured electrons when the Universe existed as a structure-less primordial plasma. These emission lines must exist if our understanding of the early Universe is correct, so a recombination line experiment will serve as a unique and powerful test of the current cosmological model. Further, a precise characterization of this spectrum will yield information about the relative abundances of hydrogen and helium in the Universe when it was approximately 380,000 years old, because these two nuclei produce unique features in the spectrum. One feature-rich section of the recombination line spectrum lies between 3.5 and 8.5 GHz, and our ultimate goal is to be the first to discover the recombination line signal by making spectroscopic measurements in this spectral band. The anticipated signal is extremely faint and therefore challenging to detect. Forecast calculations show that an array of thousands of cryogenically-cooled antenna systems will ultimately be needed to detect the cosmological signal. Therefore, a piecemeal approach that starts with the rigorous study of a single prototype antenna is appropriate. With RISE support, we will leverage exciting and ongoing R&D work in the field of silicon RF electronics for commercial wireless communication applications and develop a scalable spectrometer array element that will serve as a stepping-stone to a large array in the future.

Einat Lev, Elizabeth Hillman

Magma, the driver of volcanic eruptions, is a three-phase mixture composed of liquid melt, solid crystals, and gas bubbles. The interaction between these three components determines the style of eruption: a violent explosion, a moderately energetic lava fountain, or a quietly oozing flow. Scientists studying volcanoes have developed theories to describe how particles or bubbles move within a viscous liquid, yet models for the behavior of all three phases together are still lacking. Lab experiments using three-phase mixtures have so far been limited in their ability to directly observe these interactions–experiments have observed flow from the outside of the flow chamber, flows have been limited to only narrow, two-dimensional domains, or three-dimensional images have been made only after flow and interactions have ceased. We will be using a novel microscopy technique (SCAPE) to image, for the first time, the interaction of particles and bubbles suspended in a viscous liquid, in three dimensions and in real time. Our observations will provide constraints to models of three-phase flow and insight into magma dynamics and volcanic eruptions.

Qolamreza Razlighi, Elisa Konofagou, Ken Shepard

We propose a novel, non-invasive, whole-brain, and in vivo functional imaging method, which has the potential to provide a significantly more direct measurement of brain neuronal activity than is currently possible with BOLD fMRI alone. This method combines traditional fMRI with simultaneous real-time 4D ultrafast ultrasound Doppler imaging. The acquired imaging data will go through a set of post-processing reconstructions to generate brain functional images that measure CMRO2 at resolutions better than that achieved in BOLD signal. This functional imaging method is expected to have widespread impact on neuroscience research, providing a significant step forward in investigating neurodegenerative diseases such as Alzheimer.

Yuan Yang, Wei Min

High-performance rechargeable batteries are indispensable to a broad range of applications, including electric vehicles and grid-level energy storage. Transport of ions in battery electrolyte and their insertion into solid electrodes are critical to battery performance. For example, inhomogeneity of ion flux in the electrolyte can deplete ions locally, which not only reduces energy/power density, but also deteriorates cycling life. Therefore, visualizing and quantifying ion transport in the electrolyte and at the solid-liquid interface will not only provide better understanding of battery processes, but also help design better electrolytes and electrodes to enhance battery performance and safety. Here we propose to use the emerging Stimulated Raman Scattering (SRS) microscopy to realize such 3D imaging of ion transport in the battery electrolyte. SRS microscopy is label-free, and its dual-beam configuration employs the stimulated emission amplification, gaining 100 million times higher sensitivity than the common spontaneous Raman microscopy, which enables fast imaging at second level to resolve the transport dynamics of battery electrolyte. Such studies will deepen our understanding of battery reactions and guide further development of batteries with high performance

2016 Awardees

Columbia University Bolsters Interdisciplinary Research Collaborations with Distinctive Funding Competition

RISE competition identifies six teams to receive funding for innovative research collaboration

NEW YORK, March 3, 2016—The Columbia University Office of the Executive Vice President for Research announced today the names of six teams receiving funding through Research Initiatives in Science and Engineering (RISE), one of the largest internal research grant competitions within the University. The annual award provides funds for up to six interdisciplinary faculty teams from the basic sciences, engineering, and medicine to pursue nascent and extremely imaginative research projects. Each team’s award is worth $80,000 per year for up to two years.

The RISE competition was created in 2004 to provide Columbia faculty and research scientists with the initial funding necessary to explore paradigm-shifting and high-risk ideas. Amidst federal budget cuts for the basic sciences, researchers are increasingly challenged to provide more conclusive initial proofs of concept to demonstrate viability, even though they lack funding to complete such preliminary work. In this competition, Columbia follows the National Institutes of Health definition of high-risk research as having “an inherent high degree of uncertainty, and the capability to produce a major impact on important problems.”

“This year’s competition was exceptionally rigorous and inspiring,” says G. Michael Purdy, Executive Vice President for Research, and Professor of Earth and Environmental Sciences. “RISE is an important University program for supporting interdisciplinary scholarship, and Columbia faculty met our open challenge of conceptualizing innovative collaborations with potentially substantial impact on multiple fields. The proposed collaborations in the applicant pool spanned a total of nine individual schools and 30 departments, thus revealing an interdependent and concerted research community. Through this distinct program, we are investing in the next generation of innovative research and in the productive careers of our worldclass faculty, and we observe a positive return on our investment: We have already distributed $8.82 million in RISE funding, and, after the initial funding period has ended, these same projects have received in excess of $36 million in follow-on grants from external sponsors.”

The 2016 competition accepted 38 Round 1 applications, thereafter inviting 11 Round 2 full proposals. Applications were evaluated through two rounds of review, with at least six reviewers assigned to each second-round application. 78 reviewers—tenured or tenure-track faculty within the University—participated in selecting this year’s awarded teams.

“Research at Columbia receives Nobel Prizes; it wins prestigious center grants; it earns international praise for its impact; it ultimately obtains over $700 million in external funding every year,” says Victoria Hamilton, Executive Director of Research Initiatives, and administrator of RISE. “These accomplishments are borne of a culture of tenacious entrepreneurialism and novelty on the parts of our faculty, research scientists, postdoctoral scholars, and graduate and undergraduate students. RISE targets interdisciplinary teams who chart unknown territories. We are proud of these newly awarded teams and the 55 who came before them.”

2016 RISE AWARDEES

Designing a New Generation of Low-Power Neuromorphic Memory for Pervasive Sensing Devices Having Online Learning Ability

Mingoo Seok, Assistant Professor, Department of Electrical Engineering, The Fu Foundation School of Engineering and Applied Science

Stefano Fusi, Associate Professor, Department of Neuroscience, College of Physicians and Surgeons

Over the last four decades, pervasive sensing devices have played a crucial role in society. They have been workhorses for industrial control and infrastructure monitoring, and they are now finding applications in areas such as mobile health, unmanned vehicles, smart cities, and the Internet of Things. Designing the new generation of these devices will be extremely challenging, as they will be demanded to perform more complex and cognitive tasks with less energy budget. The approach to this challenge is to design and realize electronic devices that implement artificial neural networks using digital neuromorphic hardware. The advantage of neuromorphic hardware is energy efficiency, as it takes inspiration from the biological brain, which is far more efficient than traditional computers. One of the fundamental limitations of existing neuromorphic hardware is related to memory capacity, which can be catastrophically low when the network is required to learn online from its experience by changing its synaptic weights. This is particularly problematic when these synaptic weights have limited precision. In this project, Seok and Fusi propose to devise scalable synaptic memory models by taking inspiration from the biological synapses. The new synaptic models may be individually more complex than a conventional model, but provide significantly better scalability for storing a large number of memories in large-scale neuromorphic hardware. If successful, this proposed research can cause a ground-breaking paradigm shift by enabling synaptic memory to be compact, low power, and powerful enough to allow neural pervasive sensing devices to learn autonomously.

Listening to the Physics of Earthquakes, With Applications to Geothermal Energy Production

Ben Holtzman, Lamont Associate Research Professor, Division of Seismology, Geology, and Tectonophysics, Lamont-Doherty Earth Observatory

Douglas Repetto, Assistant Professor of Professional Practice in Visual Arts, School of the Arts

Felix Waldhauser, Lamont Research Professor, Division of Seismology, Geology, and Tectonophysics, Lamont-Doherty Earth Observatory

John Paisley, Assistant Professor, Department of Electrical Engineering, The Fu Foundation School of Engineering and Applied Science

Dan Ellis, Professor, Department of Electrical Engineering, The Fu Foundation School of Engineering and Applied Science

This project is an effort to understand how rocks fracture, by developing an entirely new approach based on how humans perceive sound. In previous work, this interdisciplinary team found that people can identify remarkable subtleties in seismic data —waves radiated by earthquakes—that is converted to sound. People identify these differences using the innate capacity to interpret physical process through sound, without knowing anything about the causes of those differences. The next step is perform experiments in which researchers squeeze and break rocks while recording the microscopic earthquakes occurring inside them. This team can identify the process causing the fracture and emitting the sound, thus being able to ask, “What aspect of the sound is being associated with a certain process?” The team will mimic this learning process with computers, using methods for pattern recognition in complex datasets. In the process, the team will be developing algorithms for the automatic remote detection of different fracture processes in the Earth. These algorithms have a very practical and potentially important application that will be pursued in this project: enhanced geothermal energy extraction involves injecting cold water into hot rock deep in the Earth’s upper crust (about 5 km) to “mine” its heat— to bring that thermal energy back to the surface where it can drive turbines and generate electricity. Geothermal energy is free of CO2 and other greenhouse gases, and is relatively inexhaustible. When cold water is injected into the crust, the water pressure and sudden temperature change can create fracture networks. The efficiency of the process depends on how well the geometry of the fracture networks and the flow of the water through them can be controlled. Identifying and understanding the fracture processes in the hot rock and controlling their transitions is where the detection algorithms will come in. Reservoir engineers will be able to make real time decisions based on the identification of fracture processes, hopefully greatly improving the efficiency of geothermal power generation.

A New Approach to Studying Natural Selection in Humans

Molly Przeworski, Professor, Department of Biological Sciences, Faculty of Arts and Sciences

Joe Pickrell, Adjunct Assistant Professor, Department of Biological Sciences, Faculty of Arts and Sciences

While there is overwhelming evidence of natural selection over long timescales and compelling examples of it operating in lab settings, in only a handful of cases has natural selection been directly observed. In humans, notably, our understanding of selection pressures acting on the genome is based on indirect statistical inferences from patterns of genetic variation and experiments in fairly distantly related species or cell lines. Przeworski and Pickrell propose a new approach: to identify variants that affect viability in extant humans by leveraging genotype data from the huge biomedical data sets now available. The idea is to mine these data sets in order to identify variants that change frequency over birth cohorts more than expected by chance, i.e., that currently affect development and aging. This approach avoids making a decision a priori about what traits matter to viability, and focus not on an endpoint (such as lifespan) but on any shift in allele frequencies with age. In addition, the researchers propose to look at how polygenic scores for quantitative traits vary with age, using sets of variants previously associated with one of >40 traits in genome-wide association studies. The team further plans to integrate phenotypic information with population genetic signals of past selection (i.e., over the past roughly 200,000 years) in order to elucidate the evolutionary history of alleles that affect human quantitative variation in these >40 traits or that impact survival. This research will lead to the identification of new loci with current effects on development and aging, as well as provide the first comprehensive look at natural selection in extant humans and its relationship to longerterm selective pressures.

Laboratory Study of Glacier-Bedrock Dynamics Using Centrifuge-Enhanced Gravity

Christine McCarthy, Lamont Assistant Research Professor, Division of Seismology, Geology, and Tectonophysics, Lamont-Doherty Earth Observatory

Colin Stark, Lamont Associate Research Professor, Division of Marine Geology and Geophysics, Lamont-Doherty Earth Observatory

Liming Li, Manager of the Centrifuge Laboratory, Department of Civil Engineering and Engineering Mechanics, The Fu Foundation School of Engineering and Applied Science

Understanding ice flow, in particular its slip over rock, is critical to a wide range of scientific problems with big societal impact—from predicting sea-level rise to assessing the health of mountain glaciers. Unfortunately, processes taking place at the glacier-bedrock interface, including erosion of the bedrock and the role of evolving bed roughness on friction, remain poorly constrained by observation, and many longheld theories have yet to be confirmed by experiment. To remedy this omission, this interdisciplinary team will design and build a novel centrifuge-based experimental apparatus to explore glacier-bedrock processes at natural spatial scales. The goal is to use enhanced gravity to study: (1) interaction between subglacial debris and bedrock, including rock abrasion and melt channel formation, and (2) interaction between basal melting and cavity formation in the lee of basal bumps. The results will contribute to the improved understanding of complex glacier dynamics and provide better parameters for future projections of glacier flow and mass balance.

Nanophotonics Platform for Enabling Memory Trace Visualization In Vivo Over a Lifetime

Michal Lipson, Professor, Department of Electrical Engineering, The Fu Foundation School of Engineering and Applied Science

Christine Denny, Assistant Professor of Clinical Neurobiology, Department of Psychiatry, College of Physicians and Surgeons The notion that memories are stored in the brain has been around since Plato, but many attempts to localize a memory trace or an engram have proved insufficient until recently. Here, Lipson and Denny define a memory trace as a population of neurons activated during learning, and whose reactivation by the original stimuli results in memory retrieval or behavioral expression. Recent techniques have allowed scientists to identify, optogenetically activate and inhibit, and alter the content of a previously learned memory. In order to visualize and manipulate memory traces, it is critical to break the tradeoff between the time at which data are acquired and the size of the imaged brain area. Currently, data can either be acquired: 1) for an entire brain but at a single time point using ex vivo postmortem techniques, such as immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO), or 2) only on a small brain region, but at numerous time points using high resolution microscopy of Ca2+ transients in awake behaving mice. Here, the team proposes to resolve this discrepancy and image whole-brain memory traces in awake behaving mice across the lifespan by developing nanowaveguides. Lipson and Denny will create a minimally invasive probe with an embedded array of microfabricated nanowaveguides, similar to nano-fibers, transparent to visible light, and with micron-size diameter. With these nanowaveguides, the team aims to optogenetically target individual neurons and to acquire large areas of activity in awake-behaving mice. Key questions could be asked, such as: How are memories stored across brain circuits? Do similar memories reactivate similar neural ensembles? How do memories change over a lifetime? How do diseases affect memory?

Imaging a Single-Molecule Circuit

Latha Venkataraman, Associate Professor, Department of Applied Physics and Applied Mathematics, The Fu Foundation School of Engineering and Applied Science

Colin Nuckolls, Higgins Professor, Department of Chemistry, Faculty of Arts and Sciences

Advances in creating new functional materials for applications in electronics, sensing, and photovoltaics rely on understanding the relation between material structure and device function. With the tremendous advances in the integrated circuits industry in the past decades, device dimensionality has shrunk into the nanometer scale. Creating innovative devices using novel materials thus requires understanding device structure at these dimensions. Here, Venkataraman and Nuckolls will develop techniques to image the structure of a single-molecule device with atomic precision using a transmission electron microscope. The ability to image these devices will not only allow researchers to “see” what has never been observed before, but, more importantly, will capture the atomic scale structure of the complex nanoscale interfaces between organic molecules and metal electrodes.

PROGRAMMATIC IMPACT

“A distinguishing factor of Columbia’s research community is its interconnectedness—faculty are very enthusiastic about new collaborations—especially across the traditional boundaries of department, school, or campus,” says Barclay Morrison, Associate Professor of Biomedical Engineering and 2015 RISE awardee. “RISE enhances this connectivity by incentivizing creativity, and we see that some of the most exciting basic research happens at the interface between disciplines. I’m a biomedical engineer, and, together with Steven Kernie, a pediatric intensivist, our RISE project explores new ways of treating cerebral edema, when a brain swells following injury. We anticipate that a range of government sponsors will be interested in the outcomes of our interdisciplinary project, which was made possible by this unique competition.” RISE not only awards critical seed funding for risky and interdisciplinary collaborations; once the funding has ceased, it tracks how the seed funding contributes to the researchers’ abilities to obtain subsequent sponsorship from government agencies and private foundations.

“Using a brand new experimental method, our project will provide fundamental understanding of the physical processes controlling glacier flow rate, which is critical to a wide range of scientific problems with big societal impact—from predicting sea level rise to assessing the health of mountain glaciers,” says Christine McCarthy, Lamont Assistant Research Professor and 2016 RISE awardee. “We have assembled an interdisciplinary team that combines the bedrock and ice specialists at the Lamont-Doherty Earth Observatory with the engineering powerhouse of the Robert A. W. Carleton Strength of Materials Laboratory to embark on this entirely novel method of testing glacier-bedrock interaction using centrifuge-enhanced gravity. Since these experiments have never been conducted, there are numerous technical challenges as well as inherent skepticism to surmount before traditional funding can be obtained. This seed funding from RISE allows us to build a prototype apparatus, and obtain the preliminary data needed to procure NSF funding and ultimately solve outstanding puzzles in glaciology.”

Since 2004, RISE has awarded $8.82 million to 61 projects. These 61 teams later secured more than $36 million from governments and private foundations: an over 400% return on Columbia’s investment. These projects have additionally garnered more than 110 peer-reviewed publications and educated more than 100 postdoctoral, graduate, undergraduate, and high school students. A complete list of RISE-funded researchers is available online.

Nominations for the 2017 competition will run from September to mid-October 2016, with five to six awarded teams announced by spring 2017.

For interview requests and additional information, contact Marley Bauce (marley.bauce@columbia.edu; 212-854-7836). To partially or fully fund a new RISE project, and learn more about supporting Columbia University’s Science Initiative, contact Sylvia Humphrey (sylvia.humphrey@columbia.edu; 212-851- 4377).

About the Office of the Executive Vice President for Research

The Office of the Executive Vice President for Research has overall responsibility for Columbia University's research enterprise, encompassing a broad spectrum of research departments, institutes, and centers in the natural and biomedical sciences, the social sciences, and the humanities. The office works to foster the continuation of those creative endeavors and to promote an environment that sustains the highest standards of scholarship, health, and safety. The office establishes and administers the policies governing the conduct of research at the University, and oversees management of its research programs. It also assists investigators seeking external funding, promotes interdisciplinary research, and awards seed money for early-stage investigations. For more information, visit http://evpr.columbia.edu.

Mingoo SeokStefano Fusi

Over the last four decades, pervasive sensing devices have played a crucial role in society. They have been workhorses for industrial control and infrastructure monitoring, and they are now finding applications in areas such as mobile health, unmanned vehicles, smart cities, and the Internet of Things. Designing the new generation of these devices will be extremely challenging, as they will be demanded to perform more complex and cognitive tasks with less energy budget. The approach to this challenge is to design and realize electronic devices that implement artificial neural networks using digital neuromorphic hardware. The advantage of neuromorphic hardware is energy efficiency, as it takes inspiration from the biological brain, which is far more efficient than traditional computers. One of the fundamental limitations of existing neuromorphic hardware is related to memory capacity, which can be catastrophically low when the network is required to learn online from its experience by changing its synaptic weights. This is particularly problematic when these synaptic weights have limited precision. In this project, Seok and Fusi propose to devise scalable synaptic memory models by taking inspiration from the biological synapses. The new synaptic models may be individually more complex than a conventional model, but provide significantly better scalability for storing a large number of memories in large-scale neuromorphic hardware. If successful, this proposed research can cause a groundbreaking paradigm shift by enabling synaptic memory to be compact, low power, and powerful enough to allow neural pervasive sensing devices to learn autonomously.

Ben HoltzmanDouglas RepettoFelix WaldhauserJohn PaisleyDan Ellis

This project is an effort to understand how rocks fracture, by developing an entirely new approach based on how humans perceive sound. In previous work, this interdisciplinary team found that people can identify remarkable subtleties in seismic data —waves radiated by earthquakes—that is converted to sound. People identify these differences using the innate capacity to interpret physical process through sound, without knowing anything about the causes of those differences. The next step is performing experiments in which researchers squeeze and break rocks while recording the microscopic earthquakes occurring inside them. This team can identify the process causing the fracture and emitting the sound, thus being able to ask, “What aspect of the sound is being associated with a certain process?” The team will mimic this learning process with computers, using methods for pattern recognition in complex datasets. In the process, the team will be developing algorithms for the automatic remote detection of different fracture processes in the Earth. These algorithms have a very practical and potentially important application that will be pursued in this project: enhanced geothermal energy extraction involves injecting cold water into hot rock deep in the Earth’s upper crust (about 5 km) to “mine” its heat— to bring that thermal energy back to the surface where it can drive turbines and generate electricity. Geothermal energy is free of CO2 and other greenhouse gases, and is relatively inexhaustible. When cold water is injected into the crust, the water pressure and sudden temperature change can create fracture networks. The efficiency of the process depends on how well the geometry of the fracture networks and the flow of the water through them can be controlled. Identifying and understanding the fracture processes in the hot rock and controlling their transitions is where the detection algorithms will come in. Reservoir engineers will be able to make real time decisions based on the identification of fracture processes, hopefully greatly improving the efficiency of geothermal power generation.

Molly PrzeworskiJoe Pickrell

While there is overwhelming evidence of natural selection over long timescales and compelling examples of it operating in lab settings, in only a handful of cases has natural selection been directly observed. In humans, notably, our understanding of selection pressures acting on the genome is based on indirect statistical inferences from patterns of genetic variation and experiments in fairly distantly related species or cell lines. Przeworski and Pickrell propose a new approach: to identify variants that affect viability in extant humans by leveraging genotype data from the huge biomedical data sets now available. The idea is to mine these data sets in order to identify variants that change frequency over birth cohorts more than expected by chance, i.e., that currently affect development and aging. This approach avoids making a decision a priori about what traits matter to viability, and focus not on an endpoint (such as lifespan) but on any shift in allele frequencies with age. In addition, the researchers propose to look at how polygenic scores for quantitative traits vary with age, using sets of variants previously associated with one of >40 traits in genome-wide association studies. The team further plans to integrate phenotypic information with population genetic signals of past selection (i.e., over the past roughly 200,000 years) in order to elucidate the evolutionary history of alleles that affect human quantitative variation in these >40 traits or that impact survival. This research will lead to the identification of new loci with current effects on development and aging, as well as provide the first comprehensive look at natural selection in extant humans and its relationship to longer-term selective pressures

Christine McCarthyColin StarkLiming Li

Understanding ice flow, in particular its slip over rock, is critical to a wide range of scientific problems with big societal impact—from predicting sea-level rise to assessing the health of mountain glaciers. Unfortunately, processes taking place at the glacier-bedrock interface, including erosion of the bedrock and the role of evolving bed roughness on friction, remain poorly constrained by observation, and many long-held theories have yet to be confirmed by experiment. To remedy this omission, this interdisciplinary team will design and build a novel centrifuge-based experimental apparatus to explore glacier-bedrock processes at natural spatial scales. The goal is to use enhanced gravity to study: (1) interaction between subglacial debris and bedrock, including rock abrasion and melt channel formation, and (2) interaction between basal melting and cavity formation in the lee of basal bumps. The results will contribute to the improved understanding of complex glacier dynamics and provide better parameters for future projections of glacier flow and mass balance.

Michal LipsonChristine Denny

The notion that memories are stored in the brain has been around since Plato, but many attempts to localize a memory trace or an engram have proved insufficient until recently. Here, Lipson and Denny define a memory trace as a population of neurons activated during learning, and whose reactivation by the original stimuli results in memory retrieval or behavioral expression. Recent techniques have allowed scientists to identify, optogenetically activate and inhibit, and alter the content of a previously learned memory. In order to visualize and manipulate memory traces, it is critical to break the tradeoff between the time at which data are acquired and the size of the imaged brain area. Currently, data can either be acquired: 1) for an entire brain but at a single time point using ex vivo postmortem techniques, such as immunolabeling-enabled threedimensional imaging of solvent-cleared organs (iDISCO), or 2) only on a small brain region, but at numerous time points using high resolution microscopy of Ca2+ transients in awake behaving mice. Here, the team proposes to resolve this discrepancy and image whole-brain memory traces in awake behaving mice across the lifespan by developing nanowaveguides. Lipson and Denny will create a minimally invasive probe with an embedded array of microfabricated nanowaveguides, similar to nanofibers, transparent to visible light, and with micron-size diameter. With these nanowaveguides, the team aims to optogenetically target individual neurons and to acquire large areas of activity in awake-behaving mice. Key questions could be asked, such as: How are memories stored across brain circuits? Do similar memories reactivate similar neural ensembles? How do memories change over a lifetime? How do diseases affect memory?

Latha VenkataramanColin Nuckolls

Advances in creating new functional materials for applications in electronics, sensing, and photovoltaics rely on understanding the relation between material structure and device function. With the tremendous advances in the integrated circuits industry in the past decades, device dimensionality has shrunk into the nanometer scale. Creating innovative devices using novel materials thus requires understanding device structure at these dimensions. Here, Venkataraman and Nuckolls will develop techniques to image the structure of a single-molecule device with atomic precision using a transmission electron microscope. The ability to image these devices will not only allow researchers to “see” what has never been observed before, but, more importantly, will capture the atomic scale structure of the complex nanoscale interfaces between organic molecules and metal electrodes.

2015 Awardees

Columbia University Fosters High-Risk Research with Funding

The RISE competition identified six winning teams to receive $80,000 per year for two years to spur innovative and unusual collaboration around basic research.

NEW YORK, June 8, 2015—Columbia University’s Office of the Executive Vice President for Research announced today the names of six teams that won the 2015 Research Initiatives in Science & Engineering (RISE) competition. Awarded annually, RISE provides funds to up to six interdisciplinary and collaborative faculty teams primarily within the basic sciences, engineering, and medicine, to pursue very early-stage, highly-imaginative research. Each team’s award is worth $80,000 per year for up to two years’ time.

The RISE competition was created to provide Columbia faculty-level researchers with the funding necessary to explore paradigm-challenging preliminary ideas, gather data, and take risks, thereby making their high-risk proposals slightly less risky. Amidst federal budget cuts for the basic sciences, researchers are challenged to provide initial proofs of concept to demonstrate viability, but without readily-available funding to complete such preliminary work. Columbia follows the National Institutes of Health’s definition of high-risk research as that “with an inherent high degree of uncertainty and the capability to produce a major impact on important problems in biomedical/behavioral research.”

“We saw an extraordinary collection of highly competitive applications this year,” says Dr. G. Michael Purdy, Executive Vice President for Research and Professor of Earth & Environmental Sciences. “The 2015 winning teams exemplify the ingenuity, creativity, and excellence that so well characterize Columbia’s preeminent research enterprise.”

The 2015 competition accepted 53 Phase 1 applications, invited 18 Phase 2 proposals, and today announces six winning collaborations.

“Together, the programs we funded this year convey the spirit and diversity of our community; from using machine learning to understand phytoplankton processes in the global ocean, to applying a new technique to understand interaction of speech perception and decision making, these researchers are driving Columbia forward in remarkable and previously-unimagined ways,” says Purdy.

2015 RISE Winning Teams

Barclay Morrison & Steven Kernie
A Novel Biomechanically-Based Approach for the Treatment of Brain Swelling After Injury

James Hone, David Schiminovich & John Kymissis
Novel Boron Nitride Deep Ultraviolet Sensors and Light-Emitting Diodes for Astrophysical & Biomedical Applications

Joaquim Goes, Tony Jebara, Ryan Abernathey & Helga Gomes
Inferring Spatial Heterogeneity in Marine Phytoplankton Using Fluid Dynamics & Bayesian Machine Learning Techniques

Nima Mesgarani & Sameer Sheth
Neurobiology of Robust Speech Perception in Human Auditory Cortex

Timothy Bestor, Jingyue Ju & James Russo
Single-Cell, High-Resolution Methylation Profiling for Personalized Medicine

Virginia Cornish & Robert Kass
Genetic Encoding of Fluorescently Labeled Membrane Proteins in Mammalian Cells for Live-Cell Imaging

Applications are evaluated through two rounds of review, with at least four peer reviewers assigned to each second-round application. 64 reviewers evaluated applications for the 2015 RISE competition.

The Impact of RISE

"RISE awards have seeded several highly interdisciplinary projects in my laboratory, which would have been impossible to initiate otherwise,” remarks Dr. Ruben Gonzalez, 2009 and 2012 RISE winner and Associate Professor of Chemistry. “These collaborations with synthetic biologists, crystallographers, and microbiologists have enabled the creation of entirely new and unique research directions in our labs. The results of these ground-breaking studies have been published in high-impact journals, have been highlighted by post-publication peer review services, and have recently evolved into established, NIH-funded research programs."

RISE not only awards critical seed funding for risky and interdisciplinary collaborations, but tracks how the seed funding contributes to the researchers’ abilities to obtain subsequent funding from government agencies and private foundations.

“Over the past decade, we see that the external funding generated as a direct result of these small, but crucial seed funds is many times that of our initial investment,” says Purdy.

Since 2004, RISE has awarded approximately $7.2 Million in seed funds to 54 individual projects. These 54 winning teams have secured more than $33 Million in supplemental funds from extramural sponsors: A nearly five times return on Columbia’s investment. These projects have also garnered more than 140 peerreviewed publications, and educated 100+ postdoctoral scientists and graduate, undergraduate, and high school students. For a full listing of all RISE-funded researchers and titles, please click here.

As Purdy notes, “RISE encourages PIs to take risks, push the boundaries of their conventional disciplines always with the goal of making fundamental new discoveries.”

Nominations for the 2016 competition will run from September to mid-October 2015, with five to six winning teams announced in June 2016.

For interview requests and additional programmatic information, please contact Marley Bauce (marley.bauce@columbia.edu; 212-854-7836). To fund a RISE project and learn more about Columbia’s Science Initiative, please contact Sylvia Humphrey (sylvia.humphrey@columbia.edu; 212-851-4377).

About Columbia University’s Office of the Executive Vice President for Research

The Office of the Executive Vice President for Research has overall responsibility for Columbia University's research enterprise, encompassing a broad spectrum of research departments, institutes, and centers in the natural and biomedical sciences, the social sciences, and the humanities. The Office works to foster the continuation of those creative endeavors and to promote an environment that sustains the highest standards of scholarship, health, and safety. The Office establishes and administers the policies governing the conduct of research at the University, and oversees the management of its research programs. It also assists investigators seeking external funding, promotes interdisciplinary research, and awards seed money for early stage investigations. For more detailed information, please visit: http://evpr.columbia.edu.

Barclay MorrisonSteven Kernie

Patients suffering from traumatic brain injury and stroke often develop elevated intracranial pressure due to brain swelling, which is highly associated with poor outcome and increased mortality. Unfortunately, current therapies to control swelling often fail or are associated with substantial adverse effects. The objective of this study is to fill this gap in critical care by testing an unconventional hypothesis about the causes of brain edema and by testing a novel therapy to control brain edema a preclinical model. Our paradigm-shifting approach targets the intracellular fixed charge density (FCD) of dead cells that we believe is thermodynamically responsible for accumulating fluid from the vasculature.

James HoneDavid SchiminovichIoannis Kymissis 

Optoelectronic technologies for the deep ultraviolet remain challenging because there are few materials that work as light emitters or sensors. We are developing a new technique to produce nano-engineered boron nitride sensors and light-emitting devices (LEDs). UV sensors will be initially designed for astronomical detection, which has a great demand for highly-efficient, visible-blind, and low-noise detectors, but these same sensors can be used for many other low cost and/or other low UV light level applications. Light emitters in this wavelength range also have a broad applicability, including use as a low-cost/high efficiency source for disinfection, for spectroscopy and fluorescence analysis, and as a low power calibration source for astrophysics

Joaquim GoesTony JebaraRyan AbernatheyHelga Gomes 

Data Sciences News Release

For the past 10 years, the Arabian Sea has been experiencing unprecedented blooms of an enigmatic planktonic organism Noctiluca, whose recent rise to prominence in the marine food chain is posing a threat to regional fisheries and the long-term health of an ecosystem which supports a coastal population of nearly 120 million. Spatial patterns of ocean phytoplankton viewable from space, have shown that each year Noctiluca make its appearance as a small patch off the coast of Oman in December; engulfing the entire northern Arabian Sea by mid-February. Despite the progress in our understanding of Noctiluca, further understanding of the dispersal patterns of this organism and its evolution to massive blooms has been hampered by difficulties in separating the influence of abiotic and biotic factors. Here we propose a study transecting the fields of fluid dynamics, phytoplankton physiology and machine learning, to unravel the rich patterns of Noctiluca patchiness in ocean color imagery. This hybrid approach could be applied to other ecosystems, especially those along the coast and in lakes that experience massive outbreaks of phytoplankton, which at times could be toxic and detrimental to human health.

Nima MesgaraniSameer Sheth 

News Story

Comprehension of spoken language is a neurological function that we often take for granted, but the underlying mechanisms are complex. Several brain regions are involved in the span of necessary processes, from parsing the basic auditory structure of syllables, to associating meaning with words and phrases, to appreciating subtle content such as innuendo, irony, and emotion. We propose to study these interrelated mechanisms by recording electrophysiological activity from several regions in the human brain. Neurosurgical procedures sometimes require the placement of electrodes within the brain, and we will use these opportunities to study human language processing with previously unavailable precision. Newly available recording techniques allow the investigation of several brain regions simultaneously, from "low-level" sensory processing to "high-level" cognitive processing. We will employ sophisticated machine learning techniques to tease apart the contributions of these various mechanisms to overall speech comprehension. We hope that the results of these studies will enhance our understanding of the normal physiology of speech processing, and also provide insight for developing therapeutic options for individuals with disorders of speech and language.

Timothy BestorJingyue JueJim Russo

The information content of the human genome is expanded by the heritable covalent modification of cytosine residues in CpG dinucleotides, a fact that has largely been overlooked in genome biology and in human genetics. Abnormal DNA methylation has long been associated with cancer, and a growing number of other human disorders have been linked to defects in genomic methylation patterns; furthermore, subtle methylation anomalies can cause genotype-independent phenotypic abnormalities. Such methylation anomalies cannot be detected by whole-genome DNA sequencing, and there is no effective means of genome-wide methylation profiling applicable to small amounts of DNA. We are developing a radically new method for whole-genome methylation profiling. The method involves the enzyme-mediated modification of all unmethylated CpG dinucleotides with an advanced photoactive compound that upon irradiation with non-genotoxic wavelengths of light will convert all unmethylated CpG dinucleotides to TpG dinucleotides. Analysis by whole-genome sequencing of the converted DNA will localize all unmethylated and methylated CpG dinucleotides in quantities of DNA found in single cells. The result will be a powerful new addition to the tools that will be used in the development and application of precision medicine.

Virginia CornishRobert Kass

A fluorescent unnatural amino acid is the smallest possible fluorescent tag for protein labeling in live mammalian cells – 100x smaller than a fluorescent protein. However, the range of fluorescent unnatural amino acids is limited, and fluorescent unnatural amino acid labeling technology in live mammalian cells is unreliable. This project aims to develop the unnatural amino acid technology as a viable, broadlyenabling small fluorescent tag for protein labeling in live mammalian cells. This tag will open up labeling of membrane proteins and enable sophisticated biophysical studies in live mammalian cells, both of which are challenging with current fluorescent protein tags.

2014 Awardees

Franklin LowyAnne-Catrin UhlemannAndrew RundleCarolyn HerzigSusan WhittierKathryn Neckerman

Infections caused by multidrug-resistant bacteria are a critical problem in healthcare settings and of increasing concern in the community. Traditional surveillance methods that focus on selected organisms do not provide insight into overall patterns of antimicrobial resistance as it emerges in different communities and strategies to track emergence and identify contributing risk factors are needed. The goal of this project is to develop an “antibiotic resistome” map of the distribution of antimicrobial resistance genes across New York City. The map will be used to identify individual and neighborhood level factors that contribute to regional differences in the distribution of these genes. Ultimately, this new approach to infectious disease surveillance could be used to develop new intervention strategies to reduce the spread of multi-drug resistant bacteria in the community

Dana Pe'erPeter Sims

Multi-cellular organisms develop from a single cell that undergoes many stages of proliferation and differentiation that result in the vast array of progenitor and terminal cell types. Regulation of this process is critical, as the slightest dysfunction can lead to a plethora of diseases, including cancer, neurodevelopmental disorders, and autoimmunity. While dogma defines development as a series of discrete steps, it is actually a continuous process characterized by transitional stages and intermediate cell types that have yet to be described. Therefore, we proposed viewing development as a dynamic continuum of states. We ordered single cells according to their developmental chronology and created a trajectory that represents all transitional states and pinpointing the precise order, timing and regulation of key events. The construction of such a map required the development of disruptive new single cell RNAseq technologies and computational approaches. To achieve this, we proposed to develop a broadly applicable set of experimental and computational tools for high-throughput transcriptional analysis of differentiating populations with single cell resolution. Specifically, we developed a microfluidic system for large-scale single cell transcriptomics that allows genome-wide quantification by RNA-Seq. The platform, when combined with statistical methods for handling low-coverage expression profiles, will make it economically feasible to sample the transcriptomes of thousands of individual cells in parallel. The tools we proposed to develop are highly general and can empower developmental studies, help elucidate how and where development is derailed in disease, be applied to cell fate determination in a variety of cellular lineages in both normal and disease contexts, and guide the next generation of regenerative medicine.

2013 Awardees

Tanya ZelevinskyDaniel Wolf Savin

The cooling of atoms with lasers has been a workhorse of atomic physics for three decades now, providing scientists with tools to create the world's best clocks, sensors, and probes of fundamental physics. Molecules have been off-limits for this technique because their rotational and vibrational motions make it difficult to scatter enough laser photons for effective cooling. Recently, it has become clear from theory and experiments that some molecules can in fact be laser cooled. In this project, we are building a cryogenic beam of hydrogen-containing molecules that are promising candidates for laser cooling and that will allow us to try new cooling and trapping approaches. These barium monohydride molecules should result in a very interesting dipolar ultra-cold gas, and could lead to improved precision measurements with ultra-cold atomic hydrogen, which has long been of interest for testing fundamental principles.

Jonathan DworkinRuben Gonzalez

Much of every cell’s energy is devoted to making proteins. Yet, little is known about the cellular mechanisms underlying a cell’s ability to turn protein production on and off during times of nutrient limitation. In 2013, Dr. Jonathan Dworkin, Associate Professor of Microbiology & Immunology, and Dr. Ruben Gonzalez, Professor of Chemistry, collaborated to study this elusive problem, and were awarded $160,000 in seed funding through the Office of the Executive Vice President for Research’s Research Initiatives in Science & Engineering (RISE) competition. Their RISE-funded research identified two regulatory factors in protein synthesis that they are now investigating as part of an R01 [GM114213-01, “Regulation of Protein Synthesis by Ser/Thr Phosphorylation”]. One of these regulatory factors allows the cell to chemically modify and inactivate the protein synthesis machinery when cellular energy intake is low, essentially putting the machinery into a sleep-like, or dormant, state. Once the cell has adequate energy intake, the other regulatory factor then reverses the chemical modification, allowing the cell to rapidly activate the dormant protein synthesis machinery and initiate the process of building new proteins. A detailed molecular understanding of the process through which the protein synthesis machinery can be switched from “active” to “dormant”, and vice versa, has the potential to unlock new avenues of basic scientific and biomedical research.

Venkat Venkatasubramanian

The recent financial crisis and ensuing sovereign debt crisis once again highlighted the great societal value of understanding the potential instabilities in the financial system. Financial instability typically results from positive feedback loops intrinsic to the operation of the financial system. The challenging task of identifying, modeling and analyzing the causes and effects of such feedback loops requires a proper systems engineering perspective that is lacking in the remedies proposed in recent literature. In this project, we developed a signed directed graphs (SDG)-based framework, a modeling methodology extensively used in process systems engineering, as an appropriate framework to address this challenge. The SDG framework is able to represent and reveal information missed by more traditional network models of financial system. This framework adds crucial information to the edges in a network in terms of the direction of flows and relationship between the variables associated with the nodes at the two ends of a directed edge, thereby providing a framework for systematically analyzing the potential hazards and instabilities in the system. This work also discusses how the SDG framework can facilitate the automation of the identification and monitoring of potential vulnerabilities.

2012 Awardees

 

Martin StuteCantwell CarsonJuerg MatterKlaus LacknerIoannis Kymissis

The project was developing an instrument to identify the ratio of carbon-14 (14C) and carbon-13 (13C) in gas samples.  Both isotopes of carbon are nearly identical chemically, but 14C has a relatively short lifetime (6000 years), and is refreshed in the environment by the interaction of cosmic radiation with nitrogen in the atmosphere.  Fossil fuels, which consist of carbon that was isolated from the atmosphere hundreds of millions of years ago, are depleted in 14C, whereas biofuels (e.g. wood pellets or ethanol) have a 14C fraction comparable to the atmospheric ratio.  It is therefore possible to confirm the biomass fraction being burned in a hydrocarbon system by sampling the emitted CO2 and determining the fraction of each isotope in the system.

This program was intended to enhance the responsivity of a sensitive instrument known as an IntraCavity OptoGalvanic Spectrometer (ICOGS), which uses a 14C laser to amplify an optical signal unique to 14C.  After a year of work and measurements taken both using the facilities at Columbia and a collaboration at Lawrence Livermore National Laboratory, it was determined that the ICOGS instrument developed does not have the sensitivity required to measure 14C in the concentrations required to detect the isotopic fraction in fuel feedstocks.  

Wei MinVirginia Cornish 

Advances in life sciences for the past half a century have been greatly facilitated by the novel physical-chemical techniques. In particular, emerging physical control or imaging methods with versatile chemical tools at subcellular level have revolutionized the way modern life sciences are conducted. This work proposed a unique hybrid genetic‐chemical strategy to achieve active control and manipulation of protein motion inside live cells by an external electromagnetic field of chemically modified magnetic tags. Its conceptual novelty and potential utility for understanding the fundamental mechanism of protein function and regulation exemplify the power with combined physical principles and chemical tags. 

Catalyzed by the interdisciplinary spirit from this RISE grant, we recently developed a super-multiplex optical imaging method for achieving simultaneous imaging of a large number of targets inside live cells. This technique again exploits the combination of novel physical spectroscopy with newly designed chemical probes, allowing for up to 24-color imaging. Such capacity breaks the
existing color-barrier in prevalent fluorescence microscopy, and will thus largely
help the understanding of complex biological systems in the era of systems biology.

Ioannis KymissisElizabeth Olsen

A cochlear implant restores hearing to a deaf individual by replacing the mechanosensing function of the ear. The device measures the sound signal with a behind-the-ear microphone and converts it into an electrical signal, which is then processed and delivered to the auditory nerve via a set of electrodes that are threaded into the cochlea. Theoretically, both the sound sensing and electrical stimulation could be done with a suitable piezoelectric material, implanted within the cochlea. Such a device would have great practical as well as cosmetic benefit. As a first step to the goal of a piezoelectric totally-implanted cochlear implant, we have used the piezoelectric polymer PVDF to make an intracochlear sound sensor. We tested this sensor first on the bench, then by rodent cochleae, and finally by human cochleae. These studies have shown the promise of the PVDF material for intracochlear sound sensing, and also the need for improvements, in particular for improved sensitivity. This improvement might be attainable through geometric or material enhancement and we continue to work on improving the PVDF intracochlear microphone, along with colleagues from Harvard Medical School.

Michael TippetSuzana CamargoAdam Sobel

Prediction of tornado activity more than a few days in advance has generally been considered difficult if not impossible. However, the record-breaking tornado activity of spring 2011 highlighted both the large impact of tornadoes on human life and property (an estimated 336 tornadoes during the April 2011 "Super Outbreak" killed 346 people and caused total damages estimated as high as $10 billion) and the difficulty of attributing the increased tornado activity to any particular climate phenomenon such as El Nino or climate change. Our 2012 RISE project proposed an approach that could lead to long-range tornado activity forecasts and explain how climate signals modulate tornado activity. In this method, tornado activity is associated with large-scale atmospheric parameters that describe the favorability of conditions for tornado activity. With RISE support, we were able to hire a post-doctoral scientist, organize a workshop, and publish results that provided credibility for our approach, allowed us to carry out the necessary work, and informed the scientific community. Subsequently, we have received federal (NOAA) and private (FM Global, Willis Re) funding. We issued an experimental forecast for seasonal tornado activity in spring 2015.

2011 Awardees

Dirk EnglundJonathan Owen

This project aimed to image neuronal signals using optically manipulated color centers in diamond. The so-called nitrogen vacancy center is the world’s most sensitive probe of magnetic and electric field probes at sub-100 nm distances. Moreover, diamond is uniquely suited for studies of biological systems because it is chemically inert, cytocompatible, and ideal for coupling to biological molecules. The project aimed to harness these properties in diamond nanoprobes with sufficient sensitivity to measure electrical signals in the brain in real-time with single-cell resolution .

Chris Marianetti

Phonons and their interactions dictate many materials properties including phase stability, thermal transport, and mechanical behavior. Furthermore, there are various experimental phenomena related to phonon interactions, such as intrinsically localized modes, which lack a firm theoretical understanding but that could have technological relevance. Our research focuses on new techniques that can reliably treat the interacting phonon problem, accounting for both the classical and the quantum regime. We have developed the so-called Slave Mode Expansion, which delivers the anharmonic interactions from first-principles energetics, and we are now broadly applying this to prototypical crystals. In order to include quantum fluctuations, we are working on extending the dynamical mean-field theory (DMFT) to the interacting phonon problem. Success of our methodology could allow for applications spanning most material systems, ranging from transition metals in jet engines to actinides in nuclear fuels to hydrogen storage materials in fuel cells.

Ansaf Salleb-Aouissi

Infant colic is defined as persistent inconsolable crying in healthy babies between 2 weeks and 4 months of age in which the baby appears to be in great discomfort and difficult to soothe. Infant colic is not a disease, but a serious and prevalent condition with serious medical and social consequences that, as of yet, remains a mystery for medical research. Estimates of the number of affected infants aged 0-4 months who cry three or more hours a day for three or more days a week for no clear cause (Wessel’s criteria), range from 5% to 40%. Medical literature on colic provides a wide range of hypotheses to explain this condition. These include lack of bacteria in the intestines, reflux, lactose intolerance, maternal smoking, and parental depression, to cite a few. A RISE award allowed us to lay groundwork to study this condition, gather a multi-disciplinary team and collect a large scale data from electronic health records. Our ongoing efforts and goals are to propose a refined diagnostic tool as well as study the underlying risk factors that lead to infant colic.

2009 Awardees

Aniruddha Das

Functional Magnetic Resonance Imaging (fMRI), the most important tool used for studying human brain function, actually measures changes in blood flow and oxygenation and not neural activity in the brain (as commonly thought). The key assumption - though untested - is that blood flow is triggered by local neural activity and is thus a reliable measure of that activity. We showed that this assumption does not always hold true. We demonstrated that blood flows to relevant brain areas in anticipation of a task, even before there is any local neural activity in those brain areas. My RISE award funded my work during the crucial initial stages of the project of exploring the basic phenomenon and describing these findings.

Raimondo BettiNicola ChiaraHaim WaismanHuiming Yin

This RISE project has supported the research team in four research frontiers: (a) An integrated sustainable economic model provides a framework to evaluate the sustainability of infrastructure considering short-, medium- and long-term effects of ­raw material acquisition, manufacture, transportation, installation, use, and recycling and waste management. (b) Investigation of the long-term performance of asphalt materials has been conducted for the life cycle cost analysis of the flexible pavement system. (c) A strain sensor and fracture indicator has been invented for structural health monitoring. (d) A multifunctional weathering system for sustainable infrastructure and energy efficient building has been designed and under development. With this support, 4 proposals have been submitted and 2 proposals are to be submitted before May, 2010. This project supported 6 undergraduate and graduate students. The PI and co-PIs have submitted or published 6 publications.

Harmen BussemakerRichard Mann

Hox genes play a central role in the development of organisms, from fruit flies to humans. With RISE funding, The Mann and Bussemaker labs jointly developed a new technology called SELEX-seq to study protein-DNA interactions at unprecedented resolution. SELEX-seq works by combining in vitro assays based on high-throughput DNA sequencing with computational analysis. By analyzing SELEX-seq data for Hox protein in complex with their common co-factor Exd, we discovered a “latent specificity” (Slattery et al., Cell, 2011) and analyzed their readout of DNA shape (Abe, Cell, 2014). We then developed open source software that is used by many other groups (bioconductor.org/packages/SELEX). The RISE funding also gave rise to an NIH-funded project (R01HG003008).

Stephen Rayport

With a 2009 RISE award, Stephen Rayport and colleagues Scott Small, Joanne Macdonald, Donald Landry, and Hadassah Tamir sought to test glutaminase (encoded by gene GLS1) inhibition for the pharmacotherapy of schizophrenia. Based on the finding that mice heterozygous for GLS1 evince a schizophrenia-resilience profile, the principal aim of the project was to conduct a high-throughput screen for glutaminase inhibiters. When the screen proved unsuccessful (as the two drug candidates identified were not confirmed in subsequent assays), further effort was devoted to testing a genetic pharmacotherapy strategy to induce a reduction in glutaminase expression. This demonstrated that glutaminase inhibition induced in adulthood attenuated amphetamine-induced hyper locomotion, a key dimension of the schizophrenia-resilience phenotype, providing further impetus for developing glutaminase inhibiters for the pharmacotherapy of schizophrenia.

2008 Awardees

Philip Kim

Benjamin O'ShaughnessyMichael SheetzJames Hone

In this program, we developed the ability to measure traction forces exerted by single cells at submicrometer length scales for the first time. We fabricated arrays of bendable pillars and cultured cells on top of them. Using bright-field optical microscopy, we tracked the deflection of the pillars as the cells pulled on them, and then calculated forces based on the known pillar-bending stiffness. By using pillars as small as 0.5 µm in diameter, we were able to observe local contractions for the very first time in which neighboring pillars are pulled toward each other. Building on this observation, we began to isolate the molecular motors responsible for these contractions, model their dynamics, and understand their role in sensing substrate rigidity. This project has led to two funded NIH R01 grants (Hone and Sheetz) that have continued to explore this fascinating phenomenon.

Elizabeth MillerJulio FernandezMichael SheetzStephen Sturley

Eukaryotic cells use membrane-bound vesicles to transport proteins and lipids within the cell. These vesicles are generated by coat scaffolds that deform the flat donor membrane into a highly curved spherical transport carrier. We aimed to investigate the biophysical basis for vesicle formation from the endoplasmic reticulum. This research program leveraged the varied expertise of the PIs to explore aspects of membrane fluidity, lipid composition and protein rigidity during vesicle formation by the yeast COPII coat.

David WaltzCatherine Schevon

The goal of the proposed research is to develop a wearable “early warning” device attached to an implantable microelectrode array that will give otherwise untreatable epilepsy patients enough time to prepare for an impending epileptic seizure. Because current intracranial EEG methods are inadequate for identifying cortical regions from which focal seizures arise, we propose that current EEG methods, such as macroelectrodes, do not have the full capacity to characterize the epileptogenic zone (EZ) from which these focal seizures arise. To overcome this problem, we are currently using a high-density twodimensional microelectrode array (MEA) consisting of 96 one-millimeter long microelectrodes arranged in a regular 10 X 10. Therefore, by using the research we are conducting to help develop a program project for effective seizure prediction, we hope to develop an implantable “early warning” device that can expand the fraction of epilepsy patients whose lives could be dramatically improved.

2007 Awardees

Steven Nowick

The goal of this research was to develop a highly-efficient asynchronous on-chip interconnection network for high-performance parallel processors. An asynchronous (i.e. clock-less) digital on-chip interconnection network promises several benefits over a traditional synchronous (i.e. clocked) approach: (i) ease of integration of multiple processor cores operating at distinct rates, using a flexible integration medium, (ii) lower power consumption, by eliminating the energy consumption of a fixed rate clock, and (iii) higher performance. As commercial single-chip parallel processors (i.e. chip multiprocessors [CMP's]) continue to scale to 10's through 1000's of cores, the integration bottleneck of such large and complex systems via a fixed-rate synchronous interconnect has become unmanageable. A variant Mesh-of-Trees network topology is targeted, and new asynchronous digital switches were developed, which support the construction of highly-efficient networks-on-chip (NoC's). Significant benefits were obtained compared to a baseline state-of-art synchronous NoC: area savings of 64-84%, power savings of 7-10x, and high-performance (nearly 2 Giga-operations/second per switch in older technology [90nm]). The successful work incubated under this Columbia initiation award was critical to obtain a subsequent medium-scale "team" NSF award (PI: Prof. Nowick, $921,686 [2008]) to further pursue this research in collaboration with a University of Maryland team (Prof. Uzi Vishkin) (http://engineering.columbia.edu/nowick-developing-new-desktop-supercomputer).

Eric Greene

My laboratory has pioneered novel technologies for studying protein DNA interactions at the single molecule level, and we use these technologies to study a number of different problems. This work entirely relies upon total internal reflection fluorescence microscopy to visualize proteins as they interact with their corresponding DNA substrates. The DNA substrates are anchored and aligned on a lipid bilayercoated surface along the leading edges of nanofabricated metallic barriers within a microfluidic sample chamber. This technology was developed using RISE funding as a flexible experimental platform adaptable to study a range of protein nucleic-acid interactions. My group is now uniquely positioned to make defining contributions to a number of fields. Specifically, we try to determine mechanistic information based upon these single molecule optical measurements, which is based upon the premise that we can determine mechanistic features of biological reactions by directly visualizing these reactions as they occur in real time. Ongoing studies include work with DNA recombination, transcription, CRISRP-Cas systems, DNA replication and chromatin biology.

Latha VenkataramanColin Nuckolls

In this proposed work, we aimed to simultaneously measure electronic and mechanical properties of single-molecule junctions using a custom built atomic force microscope (AFM). We used funds from the RISE grant to purchase parts required for the AFM and develop methods to synthesize a molecule that would function as a force-triggered single-molecule switch, and build the AFM, which has a signal to noise resolution that is far better than that of any commercial instrument. We used the AFM to correlate bond rupture forces in single-molecule junctions with molecular structure.

2006 Awardees

Victor de la PenaYochanan KushnirUpmanu Lall

The major goal of our project was to develop statistical and probabilistic tools appropriate for analyzing dynamical systems to detect changes in their spatio-temporal behavior. The results of the project are fourfold: (1) We tested a method of deriving information on gradual changes in variables related to climate projections. This was accomplished by analyzing projected drying trends in the US West and the Mediterranean. (2) In performing cluster analysis of Atlantic hurricane tracks, we tested a novel track clustering procedure based on defining moments of each track by mass and the variance of track points around this center. Identifying each historical Atlantic hurricane track by these two moments, we find an optimum of six clusters with differing genesis locations, track shapes, intensities, life spans, landfalls, seasonality, and trends. (3) In analyzing the sea surface temperature gradient along the equator to assess changes in the climate of the Indian Ocean under global warming, our recently graduated PhD candidate, Dr. Chie Ihara, identified a statistically significant weakening of the temperature gradient and the associated atmospheric features through studying the cumulative distribution function of model projected seasonal averages. (4) We are looking to adopt statistical techniques from other disciplines to approach the topic of dynamic detection of climate extremes from the perspective of decision makers looking to detect change in extreme events in a timely manner.

Zoltan HaimanLam Hui

Weak gravitational lensing is the slight distortion in the images of background galaxies. This is due to the fact that the photons emitted by these background galaxies travel on slightly curved paths predicted by general relativity through the inhomogeneous mass distribution before entering our detectors here on Earth. This project anticipated the advent of large galaxy surveys. Distortion maps of unprecedented precision, for up to a billion galaxies, will be available in the next decade from one or more of several proposed astronomical surveys. These maps are promising datasets with which to address one of the most pressing problems in physics -- the nature of dark matter and dark energy. However, current estimates of how well the dark matter and dark energy properties can be constrained have not made use of the full potential of these data. We used numerical simulations and analytical methods to study the cosmological information content of large weak lensing distortion maps, and to find the best approach to extract this information.

Dalibor SamesDavid Sulzer 

Fluorescent False Neurotransmitters (FFNs) represent a novel class of imaging probes that provide the first means to optically measure neurotransmitter release in the brain. FFNs provide neuroscience with a new experimental index: the probability of individual terminal content release. The presynaptic processes (transmitter accumulation and release) significantly contribute to synaptic plasticity, but the measurements of transmitter release from individual synapses have not been directly approachable. Recent work that extends from RISE support has enabled the first video imaging of neurotransmitter release in vivo in mice and Drosophila, and promises to make fundamental contributions to elucidating normal and diseased brain function.

2005 Awardees

2004 Awardees

Howard ShumanDavid Goldberg

A pilot program in “Earth Microbiology,” involving collaborative research at CUMC, Lamont, and Morningside campuses, was established “to investigate and understand the contribution of microbial life to the overall biology, chemistry and behavior of the earth." During this RISE-supported program, an “Earth Microbiology Initiative” (EMI) was enabled to host a variety of seminars and workshops, to seed research projects and follow-on research proposals, and to conduct cross-cutting research. Most significant research components of the program include: genetic analysis of bacteria in IODP deep ocean core samples and the microbial ecology of the Hudson River Estuary and its relationship to the the health of many people living in the NY/NJ metro area. In addition, EMI successfully promoted two seminar series, sponsored undergraduate and graduate research students, and stimulated interdisciplinary activities among researchers on three different Columbia campuses to investigating new microbiology and molecular biology approaches to environmental studies. Ongoing studies examine the water quality along the Hudson River.