Metatranscriptomic analysis to profile oral microbiome responses to broad-spectrum antibiotics during treatment of community-acquired pneumonia
The spread of antibiotic resistance is jeopardizing the efficacy of currently available antibiotics. Further complicating antibiotic therapy is a new awareness that antibiotic toxicity in non-pathogenic members of the microbiome can lead to detrimental health outcomes. To formulate therapies that have fewer complications we need to understand how untargeted bacteria respond to treatment. Metatranscriptomic analysis can profile responses in these off target bacteria and identify which bacteria are directly impacted by broad-spectrum antibiotics. We hypothesize that the differential regulation of antibiotic tolerance and resistance mechanisms can be used as a fingerprint to identify members of the microbiome that are impacted by antibiotic treatment. By conducting a community wide transcriptomic analysis of microbial populations with and without antibiotic treatment we can link well-established antibiotic response mechanisms to treatment outcomes. The key strength of this approach is that it can test antimicrobial perturbations in situ. Our initial focus will be on the oral microbiome of community-acquired pneumonia patients undergoing antibiotic treatment at Rhode Island Hospital. For this Seed project we have assembled a team that is uniquely suited to undertake this work, combining expertise in clinical infectious disease with microbiology and bioinformatics. The preliminary data and expertise obtained as part of this project will be a critical seed for the development of further work and funding opportunities. Finally, by developing sequencing and computational pipelines this project will develop capacity at Brown to study microbial flora in the context of infectious disease.
PI: Peter Belenky, Assistant Professor, Molecular Microbiology and Immunology
Co-PI: Eleftherios Mylonakis, Professor, Medicine
Assembling Complete Genomes Through Early Access to Nanopore DNA Sequencing
Despite the declining cost and increasing volume of highthroughput gene sequencing, it is still difficult and expensive to sequence and assemble genomes. Recently, we won competitive access to the initial release of a new nanopore sequencing technology (MinION) that has the promise to costeffectively read ultralong DNA fragments. These longer fragments are critical to successfully assembling complete genomes from scratch, and individual reads could potentially capture entire chromosomes. Leveraging this early access, we will research both the DNA preparation methods and data analysis methods needed to realize this promise, with immediate applications to our existing genomics projects. This interdisciplinary research will draw on expertise in biochemistry, computation, and statistics to tackle three key challenges: preserving ultralong DNA sequences so that they can be sequenced in their entirety by nanopre devices,; characterizing the signal space of the nanopore device and devloping statistical methods that align and assemble these signals; and testing hybrid assembly methods that combine nanopore sequence data with other highthroughput sequence data to assemble larger metazoan genomes. The preliminary methods and data generated by this work will enable new proposals for external funding in our groups and respective departments and strengthen pending proposals. The new computational methods developed here could result in a patent for Brown. Moreover, this work will establish a new DNA sequencing resource at Brown that will complement the existing Genomics Core Facility, can be shared by other labs with similar genomics projects, and will lead to further collaborations and funding opportunities.
PI: Susan A. Gerbi, Professor, Molecular Biology, Cell Biology and Biochemistry
CoPIs: Mark Howison, Director of Data Science, Computing and Information Services
Charles Lawrence, Professor, Division of Applied Mathematics
Benjamin J. Raphael, Associate Professor, Computer Science
Tissue Engineering for Personalized Medicine – 3D Human iPSC-Neuronal Microtissues
Modern drug development requires drug discovery, testing, and validation. It is costly and inefficient, and after drugs are brought to market, many fail. The goal of this project is to develop three-dimensional (3D) microtissues composed of patient-specific neural cells, in order to develop patient-specific disease modeling, drug testing and personalized medicine. Advantages of this approach are clear. Safety and efficacy studies on human cells can increase the likelihood of success in drug targeting. 3D cultures replicate the in vivo environment better than two-dimensional (2D) cultures, and as such, will provide more authentic assays for testing. We focus on the nervous system because there is an unmet need for fully comprehending and developing truly successful therapeutics for neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. This interdisciplinary team brings to bear the approaches of stem cell technology, neuroscience, neurophysiology, and tissue engineering on these complex problems. They will generate patient-specific neurons from human induced pluripotent stem cells (hiPSCs), including those from patients with Christianson syndrome and from their unaffected siblings. These neurons will be placed into high-throughput 3D cultures. hiPSC-neurons’ abilities to express key characteristics of neurons, including synaptic connections, will be confirmed, and their response to various drugs and disease assays will be explored. At the conclusion of this study, we will have key data to secure external funding for large-scale studies in these critical fields of research, and we will advance Brown’s position in the cutting- edge areas of pharmacogenomics and personalized medicine.
PI: Diane Hoffman-Kim, Associate Professor, Molecular Pharmacology, Physiology, and Biotechnology
Co-Investigators: Julie Kauer, Professor, Molecular Pharmacology, Physiology, and Biotechnology
Eric Morrow, Assistant Professor, Molecular Biology, Cell Biology and Biochemistry; Psychiatry and Human Behavior
Climatic and Environmental Reconstruction Using Lipid Biomarkers in Ancient Bones: Applications in Archaeology, Paleoclimatology and Paleontology
This proposed research builds on a recent exciting discovery of Professor Huang’s research group that a key class of climate-sensitive bacterial lipid compounds, is abundantly and well preserved in ancient bones. Ample research in the past few years has demonstrated that the molecular distribution of these bacteria-derived compounds in the environment faithfully records temperature and, in relatively dry regions, precipitation. Our discovery opens up a promising new avenue to extract paleoclimatic and paleoenvironmental information directly from animal or human bone samples, eliminating the key problem in environmental archaeology and paleontology of correlating such evidence directly to find contexts. Using the seed funds from Brown, we intend to demonstrate the efficacy of the new approach by analyzing a critical set of recent to modern bone samples across major climatic and environmental gradients; perform initial laboratory experiments to determine the time required for signatures to be fully registered upon bone burial in soil at controlled temperatures; analyze bone samples from important archaeological time intervals to obtain proof-of-concept data. A successful initial study as we propose here, will generate critical data with a major interdisciplinary impact that enable rapid publication of these innovative and original research technologies; they will in turn also pave the way for large collaborative research proposals across several departments at Brown to the NSF and other agencies.
PI: Yongsong Huang, Professor, Earth, Environmental, and Planetary Sciences
Co-PIs: Peter van Dommelen, Professor, Joukowsky Institute for Archaeology and the Ancient World
Andrew Scherer, Assistant Professor, Anthropology
Kevin Smith, Deputy Director and Chief Curator, Haffenreffer Museum of Anthropology
Engineering Orthogonal Ribosomes to Study Ribosome Function
The ribosome is the macromolecular machine responsible for the translation of genetic information in all forms of life. Over half of all antibiotics target the ribosome, and many are thought to act by interfering with ribosome conformational transitions. Thus deciphering the dynamic nature of the ribosome is important both for achieving a deeper understanding of a fundamental aspect of biology and for the rational design of new antibiotics. In our research collaboration, we will combine genetics with X-ray crystallography to determine the structures of ribosomes frozen in intermediate states by mutations at key functional sites. However, because the ribosome is an essential cellular component, the most informative mutations are expected to be lethal. Here, we propose to develop an orthogonal ribosome system to study ribosomes with otherwise lethal mutations. We will construct bacterial strains in which a subset of ribosomes has been altered to only translate one or more orthogonal reporter messenger RNAs. This system enables the production of ribosomes that would otherwise be toxic for the organism. The presence of compatible orthogonal reporter mRNAs and the insertion of an affinity tag further enable functional characterization in vivo as well as biochemical and crystallographic studies of these orthogonal ribosomes. After completion of the proposed work, we will be in position to submit applications to fund the long-range goals of this research program, determining the structures of ribosomes with mutations affecting conformational dynamics.
PIs: Gerwald Jogl, Associate Professor, Molecular Biology, Cell Biology and Biochemistry
Steven Gregory, Associate Professor (Research), Department of Molecular Biology, Cell Biology and Biochemistry
Exploring Innovative Delivery Methods for Brief Alcohol Interventions: The Electronic Mobile Alcohol Interventionist (EMAI)
We seek to prototype and evaluate an Electronic Mobile Alcohol Interventionist (EMAI), a robotic system that interacts with college students and helps them consider decreasing unhealthy drinking behaviors. The work is motivated by existing studies that show that robotic systems engender greater compliance than their on-screen counterparts and, at the same time, greater cost-effectiveness than therapies that require face-to-face interactions with trained experts. As a pilot study, we hope to replicate these results in an important concrete therapeutic context, specifically alcohol intervention. If successful, the project will open up opportunities for the team to seek grants at the boundary between the behavioral sciences and robotics, where novel behavioral therapies are joined with powerful new autonomous decision making algorithms to help improve health in a cost-effective manner.
PI: Michael Littman, Professor, Computer Science
Co-PI: Christopher Kahler, Professor, Behavioral and Social Sciences
Engineering Cell Morphology and Phenotype using Bioinspired Graphene Nanoarchitectures
Interactions between mammalian cells and nanoscale topographies represent an important but poorly understood signaling modality. In particular, the extracellular matrix (ECM) presents nanoscale architectural features that can direct cellular form and function, particularly during epithelial tissue remodeling and macrophage inflammatory responses. Remarkably, modern nanofabrication techniques enable artificial structures with sizes and geometries comparable to those found in the ECM. Here, we propose to explore the role of topographically patterned graphene oxide on cell morphology and phenotype. We will apply thin, stiff graphene oxide sheets to softer elastomeric substrates to generate periodic wrinkling patterns. We hypothesize that anisotropic geometries lead to the alignment and elongation of epithelial cells and macrophages. These biased nanoarchitectural cues may then alter gene expression to perturb cellular phenotype. We envision that this project will inspire new directions in nanomechanics with applications in stretchable electronics, energy storage and functional coatings. Moreover, this project will lead to new fundamental insights into how cell behaviors are modulated during embryonic development, wound healing, inflammation and cancer, with applications in designer biomaterials and regenerative medicine.
PI: Ian Y. Wong, Assistant Professor, School of Engineering; Molecular Pharmacology, Physiology and Biotechnology
Co-PIs: Agnes B. Kane, Professor, Pathology and Laboratory Medicine
Robert H. Hurt, Professor, School of Engineering
Nanoimprinted Nanowire Solar Cells
The eventual long-term goal of this research program is to create a cost-effective high-density nanowire (NW) solar cell that will exceed the so-called Shockley-Queisser power efficiency limit of ~29% for single-junction, single-crystalline silicon solar cells. The nanowire platform makes it possible to create multi-junction solar cells involving multiple materials that absorb more of the solar spectrum over a far smaller vertical cell thickness, resulting in lighter, more efficient cells. While both NWs and NW arrays have demonstrated impressive performance in the laboratory recently, cost-effective heteronanowire integration remains to be demonstrated. We have recently combined nanoimprint lithography, which permits effective fabrication of high-density (~500 nm pitch) arrays, with epitaxy (at NIST) of < 200 nm diameter Si nanowires to fabricate high-density solar cell arrays with improved efficiency over lower-density arrays grown from the usual vapor-liquid-solid (VLS) method using randomly dispersed metal seeds. Our three-dimensional finite-difference time-domain simulations show that due to diffractive scattering and light trapping, an array with 250 nm pitch should significantly outperform a blanket Si film of the same thickness – a result we plan to demonstrate experimentally during the next 6–9 months. At the same time, the small diameter of our NWs permits the combination of lattice-mismatched Ge/Si NW sections – an enabling technology for tandem Ge/Si NW solar cells combining reduced reflection with better solar spectrum coverage. The seed grant will strengthen the existing collaboration between the PIs and a National Laboratory, positioning the Brown-led team for success in extramural funding.
PI: Alexander Zaslavsky, Professor, School of Engineering; Physics
Co-PI: Domenico Pacifici, Assistant Professor, School of Engineering
Asia-Pacific in the Making of the Americas: Resources for Study
Begun three years ago by a group of Brown faculty and fellows working at the John Carter Brown Library (JCBL), the “Asia‐Pacific in the Making of the Americas: Toward a Global History” project has held six interdisciplinary, international symposia focused on transpacific interactions 1500‐1900. This Seed award will move the project to the next phase, to solidify the cohort of participating scholars through a digital publication and archive on the Brown Digital Repository. An ongoing collaboration will be established among Brown’s departments of History, English, American Studies, the Brown University Libraries and the JCBL to produce a digital multi‐authored publication that includes an archive of primary resources. This work entails close collaboration with librarians in the Center for Digital Scholarship and the JCBL. The Seed team will design and build the website using primary resources in the Brown Libraries and contributed essays, and will forge agreements with international institutional partners to add new materials to the site in the future.
PI: Evelyn Hu-DeHart, Professor, History & American Studies
Co-PIs: Caroline Frank, Visiting Assistant Professor, American Studies
Jim Egan, Professor, English
Librarians: Andy Ashton, Associate University Librarian for Digital Technologies
Elli Mylonas, Senior Digital Humanities Librarian
Jean Bauer, Digital Humanities Librarian
Rhode Island Child Obesogen Study-Pilot Phase*
Childhood obesity is the greatest public health threat to the current generation of United States children, and the identification of modifiable risk factors to prevent this epidemic is urgently needed. Prenatal insults may increase the risk of obesity by disrupting hormonally controlled mechanisms including adipogenesis, appetite, or epigenetics. Endocrine disrupting chemicals are a class of potential ‘obesogens’ that perturb these mechanisms and may increase the risk of obesity and cardiometabolic disorders. This project will build on the research infrastructure at Women and Infants Hospital Primary Care Center to conduct a pilot study and enroll 100 pregnant women at their first prenatal care clinic visit, and follow them and their offspring until delivery. Prenatal exposure to suspected contemporary endocrine disrupting obesogens will be measured. In addition, this study will measure biological intermediates involved in the development of obesity that are susceptible to endocrine disruption and associated with newborn adiposity. To ensure the associations between chemical obesogens and infant adiposity are independent of other important prenatal determinants of childhood obesity, this study will assess maternal diet, physical activity, psychosocial status, neighborhood level factors, and socioeconomic position. This cohort will serve as a resource to other Brown investigators interested in studying prenatal determinants of child and adult health.
Co-PIs: Joseph Braun, Assistant Professor, Epidemiology
Erika Werner, Assistant Professor, Obstetrics and Gynecology
Co-Investigators: Nicola Hawley, Research Fellow in Clinical Psychology
Karl Kelsey, Professor, Epidemiology & Pathology and Laboratory Medicine
Stephen McGarvey, Professor, Epidemiology & Anthropology
Maureen Phipps, Professor, Epidemiology & Obstetrics and Gynecology
Megan Romano, Postdoctoral Research Associate, Center for Environmental Health and Technology
David Savitz, Professor, Epidemiology & Obstetrics and Gynecology
Empower, Nudge: Increasing Dual Protection among Young Women in South Africa*
The overarching goal of this project is to reduce unintended pregnancies and sexually transmitted infections among young South African women, aged 18-30, who are defined as high-risk for unintended pregnancy and HIV acquisition. The main hypothesis is that a simple delivery innovation, when combined with health promotion strategies derived from behavioral economics, will motivate women’s greater uptake of effective contraception, and more consistent use over time. The specific objective is to test this hypothesis on a small-scale, in an urban setting in South Africa. This project will test a service delivery innovation, the “mini-packet,” and two kinds of innovative behavioral-economic incentives to promote initiation and adherence to voluntary contraception. A three-arm experiment in which the contraceptive packet alone will be compared against the contraceptive packet plus a loss-regret strategy (lottery), and the packet plus a standard (fixed) economic incentive will be piloted. A team of researchers from Brown and University of Cape Town (UCT) will deepen and extend cross-institution links though this multidisciplinary endeavor that incorporates distinct but overlapping research areas: behavioral and health economics, epidemiology, social and behavioral science, and behavior change.
PI: Omar Galárraga, Assistant Professor, Health Services Policy and Practice
Co-PI: Abigail Harrison, Assistant Professor (Research), Behavioral & Social Sciences
Co-Investigators: Mark Lurie, Assistant Professor, Epidemiology and Medicine
Kathleen Morrow, Associate Professor (Research), Psychiatry & Human Behavior and Behavioral and Social Sciences
Susan Short, Professor, Sociology
Brendan Maughan-Brown, Department of Economics, University of Cape Town
Scaling Evidence-Based Medicine via Automation and Crowdsourcing*
Evidence-Based Medicine (EBM) aspires to inform clinical care with all available evidence. The most important tool in the EBM arsenal is the systematic review, which provides an unbiased, comprehensive, (usually) quantitative summary of the evidence regarding a clinical question.
Producing such reviews requires exhaustively identifying relevant articles and extracting from these the data to be synthesized. These tasks have become increasingly onerous as the biomedical literature base has exploded in recent years. This Seed team will capitalize on research strengths unique to Brown in big-data, crowdsourcing and EBM, and will represent the first effort to crowdsource systematic reviews. This project will investigate the application of novel technologies (crowdsourcing, automation and hybrid strategies combining them). This research thus has the potential to greatly optimize the conduct of systematic reviews. Moreover, the proposed approach of algorithmically combining domain expertise with low-cost human computation and automation to perform high-quality work at low cost is novel from a Computer Science perspective and will have wide application. This team will procure crowdsourced annotations for two systematic review tasks. This data will be used to assess the viability of crowdsourcing for systematic reviews, and to evaluate initial hybrid human/computer strategies.
PI: Byron Wallace, Assistant Professor (Research), Health Services, Policy & Practice
Co-PIs: Thomas Trikalinos, Associate Professor, Health Services, Policy & Practice
Tim Kraska, Assistant Professor, Computer Science
Ugur Cetintemel, Professor, Computer Science
Robot Telepresence in Improved Nursing Home Organization*
Robotics is poised to be a groundbreaking technology with the potential to drastically improve outcomes, increase access, and decrease costs for healthcare. The development of smart services to care for and engage our aging population is a critical need, especially the most vulnerable and expensive-to-care-for nursing home residents. While the benefits of robotic telepresence for individual older adults have been explored, it remains unclear how effective this technology will be when scaled to the level of a nursing home. Open empirical questions revolve around the level of acceptance of these systems by the residents, staff, and administrators of these facilities, as well as their feasibility within existing facility procedures. This pilot project will study the efficacy of networked robotic services in improving the processes and organization of nursing homes and the care of older adults. The Seed team will explore the effect of using commodity robot telepresence systems for more efficient and costeffective care through telemedicine. Resulting projects will address open questions along the social, empirical, computational, engineering, design, and cost-benefit dimensions of robot telepresence in nursing homes.
PI: Odest Chadwicke Jenkins, Associate Professor, Computer Science & Engineering
Co-PIs: Michael Littman, Professor, Computer Science
Richard Besdine, Professor, Medicine & Health Services, Policy and Practice
Terrie Fox Wetle, Dean, School of Public Health
Non-Invasive Measurement of Mechanical Properties of Biological Materials
Biomimetic research studies the underlying structure and function of biological materials in order to create better biologically inspired structural materials. Hierarchical structure lies at the core of the enhanced mechanical performance of biological materials such as the strength of seashells, the elasticity of spider silk, and the crack-resistance of biological sea sponge. This project seeks to understand the structure-function connection in some of nature's archetypal structural materials ultimately achieving complete understanding of the design principles underlying natural materials to make better, stronger, tougher materials. This team will collect preliminary data by investigating the mechanical properties of the basalia spicules in the marine sponge Euplectella Aspergillum using laser light scattering spectroscopy and correlating it with theoretical and computational modeling. This unique approach will provide noninvasive, spatially resolved measurements of the in situ mechanical properties of individual components in these hierarchical structures. This information will be used to create models to explain the enhanced properties of the composite. Having established the methods with sponge spicules, this team will be positioned to expand the scope of the project into other materials.
Co-PIs: Kristie Koski, Assistant Professor, Chemistry
Haneesh Kesari, Assistant Professor, Engineering
Blindfind: Empowering the Blind to Independently Navigate Public Indoor Environments*
The BlindFind system leverages the accelerating pace of discovery in computer vision and mobile computing power for the benefit of visually impaired citizens. The project will develop a working prototype of a wearable computer-vision system and complementary geo-location mapping data repository to assist the visually impaired as they navigate public indoor environments. The BlindFind system will consist of small cameras mounted on eyeglasses, a haptic belt, an Inertial Measurement Unit worn on the belt, and a bone-conduction headphone set – all connected to a small laptop carried in a backpack. A visually impaired user equipped with BlindFind will first pilot the system in a new building with sighted assistance. The user will document key points of interest and annotate a map of the space, while the system stores and overlays landmark information within a central repository of location-specific data. Future users of the system will benefit from the annotation and other stored data; they will be presented with verbal and haptic information to guide them when they interact with the system through an audio menu. The system will respond by issuing verbal guidance and navigation assistance as necessary.
PIs: Benjamin Kimia, Professor, Engineering
Pedro Felzenszwalb, Associate Professor, Engineering & Computer Science
Enabling Autonomous Flight of Drones in Complex, Unpredictable Environments*
Tropical forests are diverse, and much of this diversity is supported by the canopy. To better understand this diversity requires better characterization of the canopy, yet no present technology allows repeatable, direct, interactive observation within and around complex canopies. Unmanned aerial vehicles (UAVs), hold great promise, but there are formidable challenges to navigating UAVs in these complex environments. What is needed is sophisticated onboard processing that characterizes the environment in 3D and makes decisions in real time about its operation in order to achieve a given objective. Existing technology is far too costly and heavy for small aircraft, and the energy requirements do not allow the UAV to operate for more than a very short period of time. This project will develop new computing solutions for real-time navigation of UAVs in these complex environments. The challenge is to use a combination of software algorithm development, customized hardware design to accelerate these algorithms, and novel design space exploration techniques that produce solutions that carefully balance navigation accuracy, system energy consumption, and realtime response rate together. The results could be generalized beyond the tropical forest, wherever real time compute-intensive processing is needed in highly constrained environments.
PI: R. Iris Bahar, Professor, Engineering
Co-PIs: Sherief Reda, Associate Professor, Engineering
James Kellner, Assistant Professor, Ecology and Evolutionary Biology
Odest Chadwicke Jenkins, Associate Professor, Computer Science & Engineering
Genome-wide sequence analysis in severe autism and intellectual disability
Autism is a relatively common cognitive development disorder that is associated with profound costs for society and families. In particular, a cohort referred to as “difficult-to-treat autism” (DTT-Autism) shows no or minimal improvements in the context of current interventions. Recent progress in genetics has highlighted the role of rare and de novo genetic variation in the development of autism, pinpointing overall mutation burden as well as numerous heterogeneous and individually rare loci. The central hypothesis of this proposal is that DTT-Autism may be sub-divided into distinct sub-diagnoses based on whole-genome sequencing (WGS) and genetic network analysis. This proposal describes two main areas of investigation: (1) WGS will be performed, which we anticipate will uncover individual genetic causes relating to DTTAutism, including potentially treatable metabolic disorders. This will guide current use of WGS in autism diagnosis. (2) Novel algorithms emerging from this team will be applied to WGS data to identify challenging-to-find variants and genetic combinations associated with DTT-Autism. This project will result in the generation of a substantial volume of sequence data that will be made available to investigators within Brown University and at surrounding Rhode Island hospitals for analysis and application to their specific research interests.
PI: Eric Morrow, Assistant Professor, Molecular Biology, Cell Biology and Biochemistry & Psychiatry and Human Behavior
Co-PI: Sorin Istrail, Professor, Computer Science
Creating a Providence-based Working Group in Precision Medicine to Identify the Genetic Determinants of Marijuana Sensitivity
This pilot technology development project will create a precision medicine working group in Providence, Rhode Island and generate preliminary data for a multi-investigator grant submission to NIH. The precision medicine working group will be organized around the problem of discovering genetic modifiers and pathways that influence the complex set of physiological/behavioral responses to Tetrahydrocannabinol (THC). The strategy will be to apply novel genomic technologies for the simultaneous sequencing and screening of genomic variants in NIDA funded study participants. The working group will leverage existing clinical histories, patient panels, DNA storage arrangements, IRB approvals, and protocols for maintaining patient contact and confidentiality. This existing clinical infrastructure is complemented by functional and computational genomics expertise. Seed funds will catalyze the collaboration between the investigators by performing exome sequencing, annotation and functional data on each variant’s effect on gene processing to create the first individual(s) genome(s) that have been characterized at a functional level.
PI: Will Fairbrother, Associate Professor, Molecular Biology, Cell Biology & Biochemistry
Co-PIs: Valerie Knopik, Associate Professor (Research), Psychiatry and Human Behavior & Behavioral and Social Sciences
John McGeary, Assistant Professor, Psychiatry & Human Behavior
Multispectral Photoplethysmography for 3D Imaging and Quantitative Assessment of Blood Flow and Oxygen Content in Bone*
The long-term goal of this project is to develop optical techniques with which to characterize important physiologic parameters non-invasively by exploiting the interaction of light with human tissues. The specific aim is to develop a photon-based device with functional capabilities for real-time, non-invasive, quantitative measurement and, ultimately, 3D imaging of blood flow and oxygen content in bone. The proposed device will consist of a flexible, planar matrix of densely integrated light emitting diodes (LEDs) and photodetectors (PDs) used to map, non-invasively, the blood flow and oxygen content in bone. The proposed project will lead to a clinically relevant technology and associated device, namely a system for 3D Multispectral Photoplethysmography Imaging (3D-MPPGI), enabling the noninvasive, quantitative description of physiologic and pathophysiologic characteristics and facilitating the early diagnosis of diseases such as osteoarthritis (OA) among other diseases of bone. This program will place Brown at the forefront of this innovative technology by creating a device that would become the state-of-the-art for measurements of circulatory physiology in tissues and would have wide-ranging clinical relevance.
PI: Domenico Pacifici, Assistant Professor, School of Engineering
Co-PI: Roy Aaron, Professor, Orthopaedics & Molecular Pharmacology, Physiology, & Biotechnology
Using big data to crack the neural code*
The goal of this project is to understand how the cortex processes sensory information during natural everyday perception. Epileptic patients with implanted intracranial electrodes offer a unique opportunity to collect neural data at both a high temporal and spatial resolution. Currently terabytes of neural data from these patients are being left unexploited because of the lack of appropriate tools to relate neural activity to natural unconstrained real world events. This team has developed new automated techniques for discovering perceptual and cognitive states during natural every day vision, and proposes to build the largest existing neural database consisting of hours of brain activity while participants watch TV together with semantic annotations of the corresponding audio and visual content. The team will make this data available to the Brown community and organize a Neural Decoding Grand Challenge. This project will catalyze the formation of interdisciplinary research teams at the interface between big data, neuroscience and computer science and build on Brown’s existing strengths to establish the university as the leader in brain mapping and neural decoding.
Co-PIs: Thomas Serre, Assistant Professor, Cognitive, Linguistic & Psychological Sciences
Nicholas Stevenson Potter, Assistant Professor, Neurology & Neurosurgery
Establishing a technique for studying the neural circuits underlying alcohol responses in flies
Understanding how activation of neural circuits elicits distinct behaviors is a daunting challenge. The Seed team brings together a leading expert in modeling alcohol responses in flies and the developer of Tango-trace, a technique for tracing circuits in flies. This project will utilize fruit flies to gain insight into the mechanisms underlying their complex behavioral responses to alcohol that are remarkably similar to the responses of mammals. Flies are the ideal model for studying the neural circuits underlying these responses because of the availability of sophisticated genetic tools for manipulating specific neurons and the ability to perform genetic screens to identify genes involved in this process. This project will establish a configuration of Tango-Trace for tracing the circuits necessary for generating long-lasting memory of intoxication. Tracing these circuits is critical for understanding (1) whether memories for aversion and reward are formed and retrieved through distinct, nonoverlapping circuits, (2) how the memory of alcohol intoxication is acquired, consolidated, and retrieved, and (3) where the output response is initiated.
PI: Karla Kaun, Assistant Professor, Neuroscience
Co-PI: Gilad Barnea, Assistant Professor, Neuroscience
*Supported through funds dedicated to following up on outstanding projects proposed during the Signature Academic Initiative process.
Opening the Archives: Access to Information, Memory, and Justice Thirty Years After the End of the Brazilian Military Dictatorship
In 2012, Brazilian President Dilma Rousseff signed an Access to Information Law, establishing guidelines for declassifying documents and opening archives containing information about human rights violations committed by the Brazilian dictatorship (1964-85). She also appointed a Truth Commission to investigate the state’s involvement in torture and repression. Green has developed a joint project with a Brazilian historian to facilitate greater access to U.S. documents on Brazil for researchers in both countries. In conjunction with the Brazilian and U.S. National Archives, this collaborative team will coordinate a group of twelve Brown and two Brazilian students that will digitize and index U.S. State Department documents on Brazil from 1960 to 1980 that will appear on websites in Brazil and at Brown. The team will also identify documents for the Truth Commission’s investigations. This effort reinforces Brown’s reputation as the leading U.S. institution focusing on contemporary Brazilian history.
PI: James N. Green, Professor, History and Portuguese & Brazilian Studies
Co-PI: Sidnei Munhoz, State University of Maringá, Paraná Brazil
Solar Power by Optical Frequency Rectification with Plasmonic Concentrators Coupled to Junctions of Doped Mott Insulators
An alternative paradigm for the conversion of solar energy to electricity makes use of the collective electromagnetic nature of solar radiation instead of individual photons as conventional photovoltaic devices do. The electric field of sunlight is first intercepted by a nanoscale antenna, and then the oscillating electrical current is rectified into a useful DC current. Optical-frequency rectification – in effect a crystal radio that runs on visible light instead of radio waves – avoids altogether the mismatch between the photon energy and the semiconducting bandgap that limits the conversion efficiency of conventional photovoltaic cells. Solar rectification thus has the potential to create a cheaper and more efficient method for the exploitation of sunlight and could lead to a paradigm shift in solar technologies. This team will design and build prototype devices that combine plasmonic concentrators / antennas with novel rectifying junctions of doped Mott insulators to test the feasibility of the concept. A working device will be a compelling argument for external funding.
Domenico Pacifici, Assistant Professor, Engineering
Gang Xiao, Professor, Physics
Three-dimensional Traction Mapping Distinguish Neutrophils from Healthy and Septic Donors
Neutrophils are the most abundant white blood cell in the circulation and are among the first cells to response to an injury or infection; they are essential for health. Patients with decreased numbers of circulating neutrophils, or with inherited defects in neutrophil functions, are susceptible to opportunistic infections and have impaired wound healing. Efforts to study neutrophils under physiologically relevant settings have found that these cells are highly sensitive to physical and biochemical cues that regulate the magnitude of the cellular response to an insult. In order to translate laboratory findings to a better understanding of how the cells function in vivo, this Seed team will study neutrophils in a three dimensional setting rather than on standard 2D surfaces. This synergistic effort between laboratories in the Departments of Surgery at Rhode Island Hospital and the School Engineering will investigate neutrophil tractions in native 3D collagen gels and quantify cellular differences between healthy and septic cells.
Phosphatase Inhibitor Design – A Unique Possibility for Brown University
The specific and reciprocal relationship between kinases and phosphatases controls most biological processes. Thus, when the balance is disrupted, the result is often disease. To date, efforts to modulate phosphate signaling to treat these diseases have focused on inhibiting kinases. However, it has recently become evident that the exquisite regulation of phosphorylation signaling is driven by tyrosine and serine/threonine phosphatases, rather than by kinases. Thus, one of the fastest growing areas of research is to identify potent, specific inhibitors of phosphatases. The Seed team will combine expertise in biochemistry, structural biology, biophysics and synthetic organic chemistry in order to develop novel, potent inhibitors of phosphatases. This project aims to develop novel peptomimetic inhibitors of the ser/thr phosphatase PP1 using data from multiple PP1 holoenzyme structures, molecularly characterize and optimize inhibitors that target the tyr phosphatase PTP1B, and develop new, potent immunosuppressant drugs using data from the ser/thr phosphatase calcineurin and chemical scaffolds already shown to target calcineurin.
Paul G. Williard, Professor, Chemistry
Making Sense of the Data Windfall: New Statistical Approaches to Evolutionary Analyses of Gene Expression
Many studies analyze gene expression to identify genes that play a functional role in particular biological processes. New tools make it possible to inexpensively measure the expression of all genes in a tissue sample. These tools, as applied in current study designs, are proving to be blunt instruments that turn up thousands of candidate genes for a particular biological process, most of which are erroneous by-catch. There is critical need to sharpen the focus of gene expression studies so that they identify a smaller set of more relevant genes. We propose to address this by adding an evolutionary dimension to gene expression studies. It will then be possible to identify speciﬁc genes that have evolutionary shifts in expression that are correlated with evolutionary changes in biological processes of interest. The hurdle to this approach is that statistical methods have not yet been developed, implemented, and tested for evolutionary analyses of high-throughput gene expression data. This project assembles an interdisciplinary team to do exactly this, and leverages Brown’s strong investments in genome sequencing and high performance computing.
PIs: Casey W. Dunn, Assistant Professor, Ecology and Evolutionary Biology
Xi Luo, Assistant Professor, Biostatistics
Zhijin Wu, Associate Professor, Biostatistics
The Role of Electrical Coupling Between Mitral Cells in Olfactory Coding*
Smell is the primary sense used by many animals to find food and mates and to avoid predators. Olfactory deficits in people are associated with loss of appetite, anhedonia and depression, and olfactory dysfunction can be an early sign of neurodegenerative diseases. The basic mechanisms by which the brain discriminates odors are obscure. Odors are detected by sensory neurons in the nose that project to special neurons called mitral cells. Patterns of mitral cell activity are transformed by the brain into the percept of a smell. Some mitral cells are electrically coupled through structures called gap junctions, also known as electrical synapses. This Seed team combines multidisciplinary expertise and the techniques of mouse genetics, electrophysiology, and behavioral analyses to study the role of electrical synapses in olfactory coding.
The Role of the Right Hemisphere in Speech and Lexical Processing*
Past research using a variety of populations and research methodologies has produced conflicting findings on the role of the right hemisphere in speech and lexical (word) processing. This project research aims to examine this question by analyzing the effects of right hemisphere lesions on speech and lexical processing in the context of current models of the functional architecture of language using state-of-the-art behavioral paradigms, measures, and neuroimaging techniques. This novel approach will add to the continued and growing strength of the Brain Sciences at Brown by contributing to the breadth of approaches used and potentially opening new directions of research examining language functions of the right hemisphere using functional neuroimaging and the application of basic research findings (bench) to language rehabilitation (bedside). Additionally, it will add a new recruiting site at the Rhode Island Hospital.
PI: Sheila E. Blumstein, Professor, Cognitive Linguistic & Psychological Sciences
Co-PIs: Lynn Fanella, MRI Senior Research Technologist/Manager
Karen Furie, Chair and Professor, Neurology
Kathleen Kurowski, Assistant Professor, Cognitive Linguistic & Psychological Sciences (Research)
John Mertus, Assistant Professor, Cognitive Linguistic & Psychological Sciences (Research)
Carole Palumbo, Boston University School of Medicine and VA Boston Medical Center
Development of New Computational and Point of Care Platforms for HIV Drug Resistance**
HIV drug resistance is a major cause of treatment failure. The ability to identify drug resistance is important in patient care, and identification of specific drug resistance mutations can assist in efficient regimen design. Resistance testing, required in developed countries, is rarely used in resource-limited settings due to financial and infrastructure constraints. This is a major hurdle in the fight against HIV/AIDS since the vast majority of this pandemic is in resource limited settings. This project builds on preliminary research and a newly-developed microfluidic method termed SMART (Simple Method for Amplifying RNA Targets), to be integrated into a point of care chip platform, for drug resistance detection in resource limited settings. This Seed team will develop a computational platform for global analysis of position-specific pol sequence variation across geographic regions within HIV1 subtypes, develop a SMART Microfluidic Platform to amplify and detect drug resistance in a full-length HIV1 plasmid, and validate the platform in HIV-infected patient samples.
Sorin Istrail, Professor, Computer Science
Joseph Hogan, Professor, Biostatistics
*Made possible through a generous donation of an anonymous donor
**Special Seed award for translational research
Climate Change, Biological Evolution, and Biogeochemical Cycles in Lakes of Central Sulawesi, Indonesia
The overarching goal of our research is to investigate coupled climatic, environmental, and biological evolution in central Indonesia over the last ~700,000 years. Indonesia lies at the heart of the Indo-Pacific Warm Pool, the largest pool of warm ocean water on Earth. Evaporation and rainfall over Indonesia controls the amount of water vapor in the Earth’s atmosphere and globally important climate processes such as the El Niño-Southern Oscillation. Long-term variations in Indonesian rainfall, combined with the tectonic evolution of the Indonesian archipelago, provide the environmental backdrop for the evolution of some of the most diverse ecosystems on Earth in Indonesia’s rainforests and lakes. We will investigate this variability by developing a Brown-led interdisciplinary science team to drill and analyze sediments from Lake Towuti, central Sulawesi, the largest lake in Indonesia.
PI: James Russell, Associate Professor, Department of Geological Sciences
Co-PIs: Anne Giblin, Senior Scientist, Marine Biological Laboratory at Woods Hole
Yongsong Huang, Associate Professor, Department of Geological Sciences
Stephen Parman, Assistant Professor, Department of Geological Sciences
Alberto Saal, Associate Professor, Department of Geological Sciences
Traffic Pollution and Acute Cardiovascular Events in Post-Menopausal Women
Cardiovascular disease is the leading cause of morbidity and mortality in the U.S. Wellenius will lead the first detailed study in a nationwide context of whether traffic pollution may increase the risk of cardiovascular events. This project will evaluate the association between long-term exposure to traffic pollution and cardiovascular risk within the Women’s Health Initiative (WHI), a large, national, prospective cohort study of 161,808 postmenopausal women. The proposed work is part of a broader research program to understand how different sources of ambient air pollution influence cardiovascular disease risk. The findings will likely have direct relevance on cardiovascular disease prevention by informing public health policy regarding the need for refinements to air pollution regulation, and position Brown University at the center of an exciting, important, and highly visible area of public health research.
PI: Gregory Wellenius, Assistant Professor, Department of Epidemiology
Co-PI: Charles Eaton, Professor, Departments of Family Medicine and Epidemiology
Eric A. Whitsel, Research Associate Professor, Department of Epidemiology, University of North Carolina Chapel Hill
Yi Wang, PhD, Post-Doctoral Research Associate, Department of Epidemiology
Melissa Eliot, PhD, Data Analyst/Programmer, Center for Environmental Health and Technology
Molecular and Cellular Mechanisms Underlying the Transition from Acute to Chronic Pain
Chronic pain is a serious health problem affecting millions of people in the USA alone. Chronic pain is highly prevalent in patients with diabetes, cancer, autoimmune deficiency, and following peripheral nerve injury. Strong evidence supports the theory that chronic pain is a maladaptive response of neurons to tissue injury or inflammation. The synapse is the site where neural transmission is scaled up and down in response to changes in neuronal input, but it is also now recognized as the critical pathological site in several brain diseases. Lipscombe and Kauer propose to begin to define fundamental cellular and molecular steps that support the development and maintenance of long-term changes in synaptic efficacy in the spinal dorsal horn, and then examine synaptic plasticity in the dorsal horn in animal models of chronic pain. The seed grant will allow them to garner preliminary data for future NIH applications.
PIs: Julie Kauer, Professor, Department of Molecular Pharmacology, Physiology, and Biotechnology
Diane Lipscombe, Professor, Department of Neuroscience
How Do Funding Mechanisms Affect Health Care Choices? Action for Health and Children’s Health in Mali
A key barrier to the cost-effective delivery of health care services in low-income countries is the lack of a full understanding of how families make decisions about when and where to seek healthcare. The aim of this project is to study these decisions in the context of children’s care. Sautmann and Dean will assess the relative importance of different factors that may affect the parents’ choice: financial constraints and costs; information and beliefs about the child’s need for care; and the preference of parents about trade-offs they must make e.g. between spending today and tomorrow, certain or uncertain outcomes or healthcare for their children versus other expenses. They frame their analysis in a dynamic model of healthcare decision-making, and use a randomized control trial of the “Action for Health” program of the Mali Health Organizing Project to estimate this model. The results will allow the researchers to predict changes in parents’ behavior and their impact on children’s health outcomes in response to different healthcare funding mechanisms.
PI: Anja Sautmann, Assistant Professor, Department of Economics
Co-PIs: Mark Dean, Assistant Professor, Department of Economics
Caitlin Cohen, M.D. Candidate, School of Medicine
The Impact of Agricultural Practices on Greenhouse Gas Emissions and Air Quality: A Case Study in New England
On a global basis, microbial activity in soils accounts for as much as 35% of nitrous oxide (N2O) emissions and nearly 20% of nitric oxide (NO) emissions. These trace gases are important in regulating Earth’s climate, while also influencing local air quality and acid rain deposition. Changes in N2O and NO emissions are anticipated with global changes in temperature, precipitation, and nitrogen fertilizer use, providing great potential for important feedbacks onto the climate and atmospheric systems. Hastings and Tang will develop a new system for automatically and simultaneously measuring the flux of N2O and NO from agricultural soils, and utilize this new technology in a pilot study to quantify the response functions of N2O and NO to parameters such as temperature, soil moisture, and nitrogen availability.
PIs: Meredith Hastings, Assistant Professor, Department of Geological Sciences and The Environmental change Initiative
Jianwu Tang, Assistant Scientist, Marine Biological Laboratory, the Ecosystems Center, and Brown Assistant Professor (MBL), Department of Geological Sciences.
Governance and Inequality in Indian Cities: A Seed Grant Proposal
Indian cities face tremendous challenges of governance because of entrenched inequalities and accelerating urban migration. Yet the social science literature on urban governance in India is conspicuous by its absence. This interdisciplinary team proposes to fill this gap through a long-term research project that is motivated by three fundamental questions. First, what are the predominant patterns of inequality in urban India and how is inequality structured? Second, how are Indian cities governed and how do these patterns of governance both reflect and impact patterns of inequality? Third, what forms of identity emerge in the migrant communities, as they come from villages to cities? And how do they view the state and fellow citizens? Who is us, who is them? This question, not often asked, is important for governance, for forms of consciousness have a relationship with what kinds of politics and political structures emerge, how political parties or civil society organizations mobilize citizens.
Novel Micropatterned Culture Model for Developing New Therapeutic Strategies for Sudden Cardiac Death
Sudden cardiac death is a leading cause of death in industrialized countries. It is most commonly caused by ventricular fibrillation, a fatal heart rhythm disturbance (arrhythmia). Emerging evidence indicates an important genetic contribution to sudden cardiac death; however, the molecular determinants have remained elusive. This project aims to develop a highly innovative and translational culture model of human cardiac arrhythmia by patterning cardiomyocytes derived from neonatal transgenic rabbits carrying a human mutation causing long QT type 2 syndrome, a common genetic cause for sudden cardiac death. Hoffman-Kim, Mende, Koren and Choi will use this new culture model to investigate arrhythmia formation, the mechanisms underlying the protective effects of progesterone as well as identify progestin molecules ideally suitable to prevent cardiac arrhythmias and sudden cardiac death in long QT syndrome.
PI: Diane Hoffman-Kim, Associate Professor, Department of Molecular Pharmacology, Physiology and Biotechnology
Bum-Rak Choi, Assistant Professor, Department of Medicine, Rhode Island Hospital
Gideon Koren, Professor, Department of Medicine, Rhode Island Hospital
Ulrike Mende, Associate Professor, Department of medicine, Rhode Island Hospital
Genetic, Biochemical, and Bioinformatic Approaches to Understanding Microbial Degradation of Plant Biomass
The development of renewable energy sources, which can supplant fossil fuels, is of utmost importance. As replacements for fossil fuels, biofuels are helping to meet the growing global demands for energy. The proposed research project will establish a conceptual framework for genetically engineering microorganisms to produce biofuels from plant biomass, a renewable and readily available source of carbon. Inspiration for this strategy comes from the abilities soil-dwelling microorganisms to degrade and consume plant biomass. We have assembled a research team with complementary and appropriate expertise to mine and elucidate the metabolic pathways for plant biomass consumption in soil-dwelling Streptomyces bacteria. By necessity, the project involves the synergistic application of experimental methods from genetics, biochemistry, computational biology, and chemistry.
PI: Jason Sello, Associate Professor, Department of Chemistry
Co-PIs: Rebecca Page, Assistant Professor, Department of Molecular Biology, cell Biology and Biochemistry
Charles Lawrence, Professor, Department of Applied Mathematics
Pollen Tube Glycobiology — A Chemical Genetic Analysis of Galactose Biochemistry in Growing Pollen Tubes
This project aims to develop pollen tube growth as a model system that uses tools of chemical-genetics to explore how cell walls are synthesized and broken down. Focusing on the role of galactose in cell wall synthesis and degradation, the project will use a combination of focused forward chemical-genetic and targeted reverse genetics methods, along with protein localization studies, to explore galactose metabolism in the context of rapid pollen tube extension. This team is dedicated to unraveling the complexities of cell wall synthesis and breakdown, work that impacts the biofuels and energy arena. The development of energy from renewable resources is one of the greatest challenges facing scientists today, and this work will help Brown establish a strong presence in this area.
Tracking Disease Spread Through the Wildlife Trade: New Techniques to Identify Infectious Microbes in Aquarium Fishes
Since 2000, the US has imported more than 1.4 billion live animals, representing thousands of species from more than 194 countries. More than 90% of these animals were aquarium fishes intended for pet shop sales. Contact with aquarium fishes is increasingly linked to human infections by bacterial species including Salmonella, Streptococcus, Mycobacterium and Aeromonas. Using intensive sampling methods and experimental manipulations, Smith and Amaral-Zettler will track changes in pathogen species richness and infection rate in select aquarium fishes as animals arrive in U.S. pet shops and are sorted into store tanks. The findings will advance the conceptual bases of disease ecology and invasion biology and inform future efforts to regulate wildlife trade to reduce disease introductions.
PIs: Katherine Smith, Assistant Professor of Biology (Research), Department of Ecology and Evolutionary Biology
Linda Amaral-Zettler, Assistant Scientist, The Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biology Laboratory; Assistant Professor, Brown-MBL Joint Graduate Program, Department of Ecology and Evolutionary Biology
Advancing Digital Scholarship with Touch-Surfaces and Large-Format Interactive Display Walls
The project will focus on the development of a prototype multi-camera large‐format display wall with gesture recognition software to be tested in tandem with the development of scholarly applications and interfaces. These powerful multi‐user, gesture‐enabled interactive display surfaces will allow the authoring and “performance” of sophisticated interactive multimedia digital projects that will be installed in libraries and other performance spaces. They will blend hypertext, static, and dynamic imagery and enable scalable visualization and remote collaborations. This multi‐faceted proposal will address research and development issues related to developing a modular, integrated platform of systems and services designed to advance digital humanities at Brown and beyond.
PI: Gabriel Taubin, Associate Professor of Engineering and Computer Science, Division of Engineering
Co-PIs: Andy van Dam, Professor of Computer Science, Department of Computer Science
Harriette Hemmasi, University Librarian, University Library
Massimo Riva, Professor of Italian Studies, Department of Italian Studies
Material Matters: A Collaboration Between Archaeology and Engineering
Rooted in existing collaborations between the Joukowsky Institute for Archaeology and the Ancient World and the Division of Engineering at Brown University, and in conjunction with Oak Ridge National Laboratory, Alcock and Sheldon will develop and refine 3-D imaging techniques for archaeological analysis. Scholars at Brown University will have the capacity to be among the very first, world-wide, to assess the significant capabilities of Dual Beam microscopy and Neutron Imaging in the three-dimensional mapping of a range of artifact types. The resulting data will be of interest to both archaeologists and material scientists whose respective fields are joined by shared interests in material culture but which at present communicate far too little.
Co-PIs: Susan E. Alcock, Director, Joukowsky Institute for Archaeology and the Ancient World, Joukowsky Family Professor of Archaeology, Professor of Classics; Professor of Anthropology; Brian W. Sheldon, Professor of Engineering
Collaborators: Krysta Ryzewski, Postdoctoral Fellow in Archaeology and Engineering, Joukowsky Institute for Archaeology & the Ancient World, Division of Engineering; Hassina Z. Bilheux, Senior Scientist and Instrument Developer, Spallation Neutron Source, Oak Ridge National Laboratory; David Paine, Professor of Engineering; John F. Cherry, Professor of Classics, Professor of Anthropology, Joukowsky Institute for Archaeology & the Ancient World; Stephen D. Houston, Professor of Anthropology
Discovering RNA Regulatory Elements in Drosophila
Conserved DNA elements that regulate gene transcription are increasingly well understood, thanks to recent advances in genome location (ChIP-chip and ChIP-seq). However, cis-regulatory elements in RNA are less well resolved, and comparable technologies have yet to be developed. With the complete genomes of twelve species of Drosophila, opportunities present themselves to leverage the data-set into testable models for new RNA control elements. Previous studies have demonstrated that splicing enhancer motifs have signature distributions relative to splice signals. The project will apply this observation to discover sequences which are important for a variety of RNA processing or regulatory events. In addition, the project will perform powerful biochemical, genetic and targeted knockout experiments to test its hypotheses.
PIs: Will Fairbrother, Assistant Professor, Department of Molecular Biology, Cell Biology, and Biochemistry;
Robert Reenan, Professor, Department of Molecular Biology, Cell Biology, and Biochemistry
The Dawn of a New Era: Deciphering the past climatic and ecological changes using integrated DNA and lipid biomarker fingerprints
This project aims to integrate state of the art DNA sequencing technology with established geochemical-paleobiological approaches to decipher past biotic and climatic changes with unprecedented specificity and accuracy. This research will demonstrate that DNA molecules preserved in anoxic lake sediments can be used to identify and quantify variations in photosynthetic microorganisms during the past ten thousand years. In addition, the project will reveal that DNA from fossil pollen grains in sediments allows quantification, at the species level, of past changes in grassland communities. The research will unite cutting-edge technologies in organic geochemistry at Brown and DNA sequencing at the Marine Biology Laboratory in an interdisciplinary collaboration.
PI: Dr. Yongsong Huang, Associate Professor, Department of Geological Sciences, Brown University
Co-PIs: Dr. Linda Amaral-Zettler, Associate Research Scientist, Marine Biology Laboratory, Assistant Professor, Brown-MBL Joint Graduate Program; Dr. Erika J. Edwards, Assistant Professor, Department of Ecology and Evolutionary Biology; Dr. James Russell, Assistant Professor, Department of Geological Sciences
A New Method for Evaluating Vitamin D levels in Serum and Saliva
The ability to measure vitamin D levels accurately is an important tool in combating the increasing number of diseases associated with vitamin D deficiency. The project plans to develop a hand-held device that measures the level of vitamin D in a sample of serum or saliva from a patient, similar to a commercial glucose meter. Additionally, the integration of the platform with conventional MEMS technology will enable the construction of a miniaturized biosensor that can be mass-produced at low cost. Based on our preliminary results, a patent application has been filed, placing Brown at the forefront of research in electrochemically-based vitamin D sensors.
PI: G. Tayhas R. Palmore, Professor of Engineering, Professor of Medical Science, Division of Engineering
Co-PI: G. Satya Reddy, MD, Epimer, LLC, Adjunct Professor, Department of Chemistry International collaborator: Professor Toshiyuki Sakaki, Biotechnology Research Center, Toyama Prefectural University
Molecular Analysis of a Bistable Switch in the Pathogen Candida albicans
Candida albicans is the most commonly isolated fungal pathogen and is responsible for debilitating mucosal infections as well as life-threatening systemic infections. Despite its prominence as a human pathogen, relatively little is known about virulence factors in C. albicans compared to bacterial pathogens. One feature of Candida biology that has been linked with pathogenicity is phenotypic switching, in which strains convert rapidly and reversibly between alternative phenotypic forms. This proposal will examine one such phenotypic transition, the white-opaque switch, which influences both the virulence of C. albicans strains and their ability to form biofilms.
PI: Richard Bennett, Assistant Professor of Biology, Department of Molecular Microbiology & Immunology
Co-PIs: Jeffrey Laney, Assistant Professor of Biology, Department of Molecular Biology, Cell Biology, and Biochemistry; Suzanne Sindi, Prager Assistant Professor of Applied Mathematics, Division of Applied Mathematics; Joseph Bliss, Assistant Professor of Pediatrics, Department of Pediatrics; Nicola Neretti, Assistant Professor of Brain & Neural Science (Research), Institute for Brain & Neural Systems
This project will use Geographic Information Systems (GIS) to plot the landscape of a French abbey as a monastic eco-system. Diverse disciplines will converge to place the lands, parishes, and other dependencies of Saint-Jean-des-Vignes into the larger regional and European context. Visual data from the long tradition of mapping in Europe , such as seventeenth-century maps, land registries and charters, will be correlated with GIS data. Brown's strengths in both population studies and spatial analysis provide unique support for this endeavor.
PI: Sheila Bonde, Dean of the Graduate School ; Professor of the History of Art and Architecture, Department of the History of Art & Architecture; and Professor of Archaeology, Joukowsky Institute for Archaeology and the Ancient World
Co-PIs: Clark Maines , Professor of Art History, Art and Art History Department, Wesleyan University ; Elli Mylonas, Associate Director, Computing and Information Services
Pilot research to inform a childhood obesity prevention study to improve the nutrition and physical activity environments of low income children
Childhood obesity is an escalating public health problem, especially for low income and ethnic minorities. There is a pressing need to develop and evaluate effective, practical, sustainable interventions to prevent childhood obesity with these populations. An interdisciplinary team of Brown faculty from multiple departments and centers will conduct research to develop interventions to improve the nutrition and physical activity environments of low income, ethnically diverse families and to inform a future randomized controlled trial that will test the efficacy of these interventions. This research will advance Brown's position in the field by developing expertise in multi-level community-based approaches to prevent childhood obesity, establishing a national reputation in this research area, and fostering Brown's ties with the community on this critical public health issue.
PI: Kim Gans, Associate Professor of Community Health (Research), Department of Community Health, and Deputy Director, Institute of Community Health Promotion
Co-PIs: Michael J. Mello, Assistant Professor, Departments of Emergency Medicine and Community Health, Director of the Injury Prevention Center at Rhode Island Hospital; Bess H. Marcus, Professor, Departments of Psychiatry & Human Behavior and Community Health; Linda Shalon, Associate Professor of Pediatrics (Clinical), Attending Physician, Hasbro Children's Hospital Department of Pediatric Gastroenterology, Nutrition, and Liver Diseases, and Medical Director, Kids on the Move, RI
High–Resolution X-ray Imaging of Tumor Angiogenesis
This project will pair a new tissue preparation method with state-of-the-art x-ray imaging in the study of liver cancer. The research will afford a detailed look at blood vessel formation using images with hundreds of times higher resolution than that of conventional x-ray images. This effort involves collaboration between the Liver Research Center at Rhode Island Hospital , and Brown University through the Warren Alpert Medical School and the Department of Chemistry.
Co-PIs: Gerald J. Diebold, Professor of Chemistry, Department of Chemistry; Christoph Rose-Petruck , Associate Professor of Chemistry, Department of Chemistry; Jack R. Wands, Jeffrey and Kimberly Greenberg-Artemis and Martha Joukowsky Professor in Gastroenterology, and Professor of Medical Science, Brown Medical School, Professor, Department of Molecular Microbiology & Immunology, and Director, Liver Research Center, Rhode Island Hospital
Developing Highly Efficient Non-Pt Nanoparticle Catalyst for O2 Reduction and CO Oxidation
This joint proposal with the Oak Ridge National Laboratory will research nanoparticles toward applications in fuel cells. Specifically, the project will create and evaluate a new catalyst for fuel cell reactions that is not based in platinum. Brown will synthesize and characterize the catalyst while the national laboratory will evaluate its activity. This collaboration will ultimately foster a multi-disciplinary team to develop alternative catalysts for fuel cells.
PI: Shouheng Sun, Professor of Chemistry, Department of Chemistry
Co-PI: Sheng Dai, Leader, Nanomaterials Chemistry Group, Chemical Sciences Division and Center for Nanophase Materials Sciences, Oak Ridge National Laboratory
Transcript Turnover in the Egg-to-Embryo Transition: Basic and Clinical Applications
The growing number of patients seeking assisted reproductive procedures underscores a critical need for a sensitive method to predict an embryo's successful development. Currently, clinicians rely strictly on a visual assessment to decide which and how many embryos to implant. However, the high risks and ethical, emotional, and developmental issues demand more of the clinician. Improved technology and a better understanding of the embryo can enable a more stringent evaluation for embryo prioritization. This collaboration between a clinician, three basic biologists, and two computational molecular biologists will study the mechanism of the oocyte-to-embryo transition and develop a molecular tool to help clinicians.
PI: Gary Wessel, Professor of Biology, Department of Molecular and Cell Biology & Biochemistry
Co-PIs: Mark C. Alliegro, Senior Scientist, Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory; Sandra Carson, Professor of Obstetrics and Gynecology, Brown Medical School, and Director of the Division of Reproductive Endocrinology and Infertility and the Center for Reproduction and Infertility at Women & Infants Hospital; Richard Freiman, Assistant Professor of Medical Science, Department of Molecular Biology, Cell Biology and Biochemistry; Charles Lawrence, Professor of Applied Mathematics, Division of Applied Mathematics; William Thompson, Assistant Professor of Applied Mathematics (Research), Center for Computational Molecular Biology and Division of Applied Mathematics
Toward a Closer Alignment between High School and University Curricula: A Pilot Study on International Comparison in Students' Study of Chemistry
This collaborative effort between the Education and Chemistry departments will examine the secondary education systems of nations that consistently outperform the US in 8th grade to determine the differences in their science curricula. This research will position the team to develop a chemistry curricular framework for U.S. secondary schools-and urban schools in particular-that prepares students for university-level scientific study.
PI: Kenneth Wong, Walter and Leonore Annenberg Chair for Education Policy Professor of Education, Political Science and Public Policy & Director of Urban Education Policy Program, Department of Education
Co-PI: Peter M. Weber, Chair, Department of Chemistry
Integrin Mediated Adhesion and Retraction during T Cell Migration
Using newly developed biophysical and engineering tools, an interdisciplinary team of physicists, engineers and hospital-based research faculty will study the forces involved in the adhesion and migration of T cells. These tools will allow for the visualization and tracking of specific proteins such as integrin, which are involved in adhesion during migration. The knowledge acquired will be pertinent to understanding the precise mechanisms used by immune cells to fight infectious diseases.
PI: Jay X. Tang, Assistant Professor of Physics and Engineering, Physics
Co-PIs: L. Ben Freund, Henry Ledyard Goddard University Professor, Mechanics of Solids and Structures, Division of Engineering; Minsoo Kim, Assistant Professor, Department of Surgery, Brown Medical School; Jonathan Reichner, Associate Professor, Department of Surgery, Brown Medical School
Evolutionary Response to Nanomaterial Exposure in the Environment: Functional Genomics of C60-Resistance in Drosophilia
The release of nanoparticles to the environment could have significant impacts on the genetic composition of natural communities. Using fruit flies as a model system, this project will address the ecotoxicological effects of Buckminster fullerene (C60) exposures to determine the long-term environmental effects on the genetic variation in populations. This project will further current nanotoxicology research by adding a novel ecological and evolutionary component and will enhance the work of Brown's emerging cross-departmental center, the Alliance for Molecular and Nanoscale Innovation.
PI: David Rand, Professor of Biology, Department of Ecology and Evolutionary Biology
Co-PIs: Kristi Wharton, Associate Professor of Biology, Department of Molecular Biology, Cellular Biology and Biochemistry; Robert Hurt, Professor of Engineering, Division of Engineering
Developing an Integrated Genomic Approach to Explore the Antitumor Activity of Vitamin D and Derivatives to Treat Ovarian Cancer
The goal of this project is to take a global genomic view to understand the effect of vitamin D and the vitamin D derivative, MT19C, on ovarian tumors. This cross-disciplinary team of experts from molecular biology, chemistry, mathematics and medicine will combine complementary genomic technologies to understand how cells respond to vitamin D. This research will provide important insights to develop novel therapeutic treatments for ovarian cancer.
PI: Alexander S. Brodsky, Assistant Professor of Medicine, Department of Molecular and Cell Biology and Biochemistry
Co-PIs: Laurent Brard, Assistant Professor and Director of the Molecular Therapeutics Laboratory at Women & Infants Hospital of RI; Charles Lawrence, Professor of Applied Mathematics; Richard Freiman, Assistant Professor of Medical Science, Department of Molecular and Cell Biology and Biochemistry
Carbohydrate-binding Flourescent Nanoparticles: an Enabling Technology for Glycomics
This project brings together chemists, pathologists and biologists interested in studying cell surface carbohydrates and their functions. Using the tools of quantitative fluorescence microscopy and pattern recognition algorithms, this team will generate more accurate descriptions of cell surface carbohydrate compositions. This knowledge will contribute to a strategy for diagnosing cancer at the molecular level and for understanding the basic glycobiology of plant development.
PI: Amit Basu, Associate Professor, Department of Chemistry
Co-PIs: Douglas Gnepp, Professor, Department of Pathology, Brown Medical School and Rhode Island Hospital; Mark Johnson, Assistant Professor, Department of Molecular Biology, Cell Biology and Biochemistry; Matthew Zimmt, Professor, Department of Chemistry
Targeted Research Seed Fund Award for Energy Research:
Development of a "Spouted Bed" Direct Carbon Fuel Cell (SB/DCFC)
In 2005, one billion tons of coal were consumed in the US for electricity generation. Given the increasing demands for electricity and the constraints on natural gas and nuclear power, coal will continue to play a very important role in the energy future of this country. In conjunction with Oak Ridge National Laboratory, this research is focused on the construction and characterization of a prototype of a new kind of direct carbon fuel cell (DCFC) that is being developed to circumvent some of the more important shortcomings of current DCFC designs. DCFCSs are electrochemical devices that produce electricity directly from carbonaceous sources, such as coal and biomass, without combustion or gasification. With much higher theoretical efficiencies than thermal power plants, DCFCs can significantly reduce CO2 emissions, as well as many other pollutants generated by conventional coal-fired power plants.
PI: J.M. Calo, Professor of Engineering
Co-PI: E. Bain, Postdoctoral Research Associate, Division of Engineering
Targeted Research Seed Fund Award for Scientific Computing:
The Cellarium Project: A Teaching and Research Environment for Computational Systems Biology
The goal of this project is to build a novel research environment that will address unmet challenges of computational and systems biology in the post-genome-sequence and systems biology era. Building on Dr. Istrail's experience in leading the construction of some of the most powerful genomics suites of tools to date, for whole genome comparison, annotation and analysis, and his biological systems research in protein folding and misfolding, and gene regulatory networks, he will collaborate with scientists at Oak Ridge National Laboratory and California Institute of Technology to develop new computational environments for molecular reconstruction. This project will involve the world's most powerful accelerator-based neutron source to create an environment where for the first time, researchers can computationally reconstruct in vivo protein folding.
PI: Sorin Istrail, Julie Nguyen Brown Professor of Computational and Mathematical Sciences, Professor of Computer Science, Director of the Center for Computational Molecular Biology
Development and Verification of CTX Imaging for Musculoskeletal Biomechanics Research
This team, composed of zoologists, bioengineers and a computer scientist, is collaborating on the development of “CTX,” a new biomedical imaging technology for dynamic visualization of bones and joints in motion. With this advanced technology researchers will be able to look inside living humans and animals and see their skeletons moving in 3D. This new technology will find broad application in orthopedics and zoological biomechanics research, and possibly lead to clinical diagnosis and treatment of orthopedic problems.
PI: Elizabeth Brainerd, Professor, Ecology and Evolutionary Biology
Co-PIs: Joseph J. Crisco, Associate Professor, Orthopedics; Braden C. Fleming, Associate Professor, Orthopedics; Stephen M. Gatesy, Associate Professor, Ecology and Evolutionary Biology; David H. Laidlaw, Associate Professor, Computer Science; Douglas C. Moore, Associate Director of Bioengineering Laboratory, Orthopedics; Thomas J. Roberts, Assistant Professor, Ecology and Evolutionary Biology; Sharon M. Swartz, Associate Professor, Ecology and Evolutionary Biology
Nanoscale Biomimetic Materials for Nerve Regeneration
The goal of this project is to determine the critical cues needed to guide nerves, thus providing essential information for new strategies for nerve regeneration. This interdisciplinary team from Molecular Pharmacology, Physiology and Biotechnology and the Division of Engineering, hopes to converge synergistically to develop and fabricate novel biomimetic biomaterial systems with drug delivery capabilities, to characterize these biomaterials in vitro, and to evaluate them in in vivo models of nerve injury.
PI: Diane Hoffman-Kim, Assistant Professor, Molecular Pharmacology, Physiology and Biotechnology
Co-PIs: Thomas Webster, Associate Professor, Engineering; Edith Mathiowitz, Professor, Molecular Pharmacology, Physiology and Biotechnology; Moses Goddard, Associate Professor (Research), Molecular Pharmacology, Physiology and Biotechnology
Exceptional Children — Exceptional Challenges: Developing an Interdisciplinary, Multinational Project for Studying Work-Family Dilemmas among Parents Raising Children
This team of sociologists, along with an economist and pediatrician, will undertake an innovative pilot study to gather preliminary research on the prevalence and types of child disability, the choices families make to meet conflicting family economic needs and time constraints, and the relative public and private costs of raising children with disabilities. The emphasis will be on the analyses that contrast and compare varying societies, starting with a U.S.-Australia comparison analysis of work/family dilemma.
PI: Dennis P. Hogan, Professor, Sociology
Co-PIs: Anna Aizer, Assistant Professor, Economics; Peter D. Brandon, Adjunct Associate Professor, Populations Studies and Training Center, and Australian Professorial Fellow and Professor of Demography and Sociology, Research School of Social Sciences, the Australian National University; Patrick Heller, Associate Professor, Sociology; Michael E. Msall, Professor of Pediatrics, Pritzker School of Medicine, University of Chicago; Susan Short, Associate Professor, Sociology
Structural Biology and Function of Macromolecular Complexes. Using Dynamic Light Scattering to Initiate the Establishment of a Brown University Facility for State-of-the-Art Biophysical Protein Characterization
This undertaking will add essential instrumentation to the cross-disciplinary and inter-disciplinary Laboratories of Molecular Medicine (LLM), which is home to a diverse set of faculty whose research interests span all levels of biology. The acquisition of a dynamic light scattering (DLS) instrument will facilitate key collaborative research studies of eight primary uses and help to establish a centralized facility for protein biophysical characterization.
Co-PIs: Laurent Brossay, Assistant Professor, Molecular Microbiology and Immunology; Albert E. Dahlberg, Professor, Molecular Biology, Cell Biology and Biochemistry; David E. Cane, Professor, Chemistry; Dale F. Mierke, Associate Professor, Molecular Pharmacology, Physiology and Biotechnology; Wolfgang S. Peti, Assistant Professor, Molecular Pharmacology, Physiology and Biotechnology; Anatoly Zhitkovich, Associate Professor, Pathology and Laboratory Medicine
Brown Influenza Microchip: Rapid Identification of Sequence Specific Subtypes
In this project, the Division of Engineering teams up with Medical School faculty to develop an Influenza Detection Microchip capable of rapidly identifying influenza subtypes, which is not currently possible outside of specialized labs. This new technology aims to provide health care and public health professionals with key information for determining a public health response appropriate to the viral threat.
PI: Anubhav Tripathi, Assistant Professor, Engineering
Co-PIs: Andrew W. Artenstein, Associate Professor, Medicine; Steven M. Opal, Professor, Medicine
Brown University – Rhode Island Hospital Cooperative Research Network: A research problem selection paradigm based on medical needs
PIs: Gregory Crawford and Eric Suuberg, Engineering
Metrics for Quantifying White Matter Variation: image analysis, testing, and application
PI: David Laidlaw, Computer Science
Development and Optimization of Novel Chemotherapeutic Agents for Cancer
PI: Narasimha Swamy, Pediatrics
Quantitative Neuroimaging of Object Representation and Perceptual Decision-Making
PI: Luiz Pessoa, Psychology
Co-PIs: Michael Tarr, Cognitive and Linguistic Sciences; David Ress, Neuroscience
Using Physiological Measurements and Artificial Neural Networks to Monitor and Predict Cognitive States
The Ersatz Brain Project: Brain-Like Computer Design for Cognitive Applications
PI: James Anderson, Cognitive & Linguistic Sciences
Co-PIs: Gerald Guralnik, Physics; James O'Dell, TCASCV
Strengthening Brown University Vaccine Development Capability. A Collaborative for Vaccine Research and Development (CVRD)
PI: Anne De Groot, Community Health, TB/HIV Research Lab
Co-PIs: Luisa Marcon, Community Health; Steven Gregory, Molecular Biology, Cell Biology and Biochemistry, Liver Research Center; Jan Klysik, Molecular Biology, Cell Biology and Biochemistry, Transegenic Mouse Facility; John Sedivy, Molecular Biology, Cell Biology and Biochemistry; Steven Opal and Andrew Artenstein, Medicine; Georges Peter, Pediatrics
Management of the Wadi Khalil/Nahal Besor Environmental Borderscape
PI: Steven Hamburg, Environmental Studies, Ecology and Evolutionary Biology, and Watson Institute
Co-PIs: Brian O'Neill, Watson Institute; Rachel Morello-Frosch, Environmental Studies and Community Health; Jeff Albert, Geological Sciences and Environmental Studies; Calvin Goldscheider, Sociology and Judaic Studies
Development and Validation of a Gene Expression Profile for Identification of Potentially-Carcinogenic Nanofibers
PIs: Agnes Kane, Pathology and Laboratory Mediineand Robert Hurt, Engineering
Co-PIs: Constantine Gatsonis and Suddhasatta Acharyya, Community Health
Impact of Adolescent Pregnancy Intention and Stress of Poor Birth Outcomes
PI: Maureen Phipps, Obstetrics and Gynecology, and Community Health
Co-PIs: Jenifer Allsworth, Gerontology Health; Jeffrey Peipert, Obstetrics and Gynecology; Caron Zlotnick, Psychiatry and Human Behavior; Geralyn Messerlian, Pathology and Laboratory Medicine; Sherry Weitzen, Obstetrics and Gynecology; Jeffrey Blume, Community Health
Neuroproteomics of Learning and Addiction
PI: John Marshall, Molecular Pharmacology, Physiology & Biotechnology
Co-PIs: Dale Mierke, Molecular Pharmacology, Physiology and Biotechnology; Mengia Pedotti-Rioult, Molecular Pharmacology, Physiology and Biotechnology; Gary Kaplan, Psychiatry & Human Behavior; Julie Kauer and Leslie Blair, Molecular Pharmacology, Physiology and Biotechnology; Zixu Mao, Medicine; Anna Dunaevsky, Neuroscience
Microsphere – Based Drug Delivery Systems and Hydrogels for the Creation of Cartilage Biocomposites. A Tissue Engineered Solution to Joint Damage
PI: Clyde Briant, Engineering
Co-PIs: Kenneth Breuer, Engineering; Diane Hoffman-Kim, Molecular Pharmacology, Physiology and Biotechnology and Engineering; Jeffrey R. Morgan, Molecular Pharmacology, Physiology and Biotechnology; G. Tayhas R. Palmore, Engineering, Biology and Medicine; Thomas R. Powers and James R. Rice, Engineering
Transient Hearing Loss and Milestones of Language Learning
PI: James Morgan, Cognitive and Linguistic Sciences
Co-PIs: Katherine Demuth, Cognitive & Linguistic Sciences; Cynthia Garcia Coll, Education, Psychology and Pediatrics; Michael E. Msall, Child Development Center, RIH; Ronald Seifer, Psychiatry and Human Behavior, Center for the Study of Human Development
Understanding and Modeling Land Cover-Land Use Change
PI: John Mustard, Geological Sciences
Award: $83,578, with an additional $10,000 to incorporate the proposal of Warren Prell, “Understanding Eutrophication and Hypoxia in Narragansett Bay: An Initiative to strengthen Brown’s Estuarine Research Efforts.