Analysis of the Initiation of an HIV Broadly Neutralizing Antibody Lineage in a Single Host

SPONSOR: National Institutes of Health
AWARD DATE: 3/23/2020

Human immunodeficiency virus (HIV) is a rapidly evolving pathogen that escapes immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies (bnAbs) by vaccination require a deeper understanding of evolution of the immune response to infection, since these protective antibodies typically take ~4-5 years to develop. In HIV-infected individuals, viruses and antibody producing B-cells evolve together, creating a virus-antibody “arms race,” with populations of viruses and antibodies present throughout infection. This research will analyze critical early time-points of the arms race in a donor who developed antibodies of significant breadth, to guide immunogen design. Undergraduate research students supported by this Academic Research Enhancement Award (AREA) from the National Institute of Allergy and Infectious Diseases (NIAID) will explore an issue of critical public health importance using cutting-edge techniques, be co-authors on published work and be mentored by experts committed to their long-term career development.

PROJECT PERIOD: 4/01/2020 – 3/31/2023

Collaborative Research: RUI: Jammed granular matter within networks of pins: Structure, elasticity, plasticity and rheology under shear

SPONSOR: National Science Foundation
AWARD DATE: 11/25/2019

This study aims to engage computational and experimental studies in the active, modern fields of jamming and clogging, employing a novel strategy of imposing controlled pinning sites. Such a study will not only elucidate these transitions, but provide a step towards applications in which pinning sites may be used to broadly control the rheology of a granular sample, with likely extensions to related areas of soft condensed matter, physics of life, and the engineering of novel materials. In this Research in Undergraduate Institutions (RUI) project, an experimentalist and theorist at each institution (Bucknell University and Swarthmore College) will work collaboratively, both within and between institutions. Fifteen summer undergraduate research associates and roughly half that many students supported during the academic year will be actively involved in all facets of the proposed work, including direct collaboration across two institutions on both experiments and simulations. 

PROJECT PERIOD: 12/01/2019 - 11/30/2022

Signal-dependent regulation of chordate heart gene networks

SPONSOR: American Heart Association
AWARD DATE: 12/26/2019

Signaling between cells plays a key role in heart development. However, the mechanisms that mediate precise transcriptional changes downstream of these cardiogenic signals remain poorly characterized. Deciphering how cardiogenic signaling coordinates heart gene expression is essential for the diagnosis and treatment of congenital heart disorders. Our long-term goal is to gain a comprehensive understanding of cardiogenic signaling and how it impacts chordate heart gene networks. The complexity of this process in vertebrate embryos has hindered progress. We have begun to exploit the simplicity of Ciona robusta, a close evolutionary relative of the vertebrates, to investigate a conserved role for the signal dependent transcription factor, Ets, in early heart development. This AHA Institutional Research Enhancement Award (AIREA) will be tailored to promote intensive training of undergraduate researchers in the formulation and execution of independent research projects.

 Project Period: 01/01/2021 - 12/31/2021
 

Comparative mechanistic study of developmental neurotoxicity of organophosphorus pesticides

SPONSOR: National Institutes of Health
AWARD DATE: 12/25/2019

Organophosphorus pesticides (OPs), a large and chemically diverse class, are the most commonly used and economically important insecticides worldwide, accounting for approximately 40% of recently used insecticides in the U.S. While legal OP concentrations are not acutely toxic to humans, studies suggest that chronic prenatal and infant exposures can lead to life-long neurological damage and behavioral disorders. Acute OP poisoning due to inhibition of acetylcholinesterase (AChE) is well-understood. But, despite decades of OP research, it remains debated whether and how subacute OP exposure at regulated levels that do not significantly inhibit AChE causes morphological and cognitive defects in the developing human brain. We will investigate whether phenotypic differences of OP DNT result from interactions with different molecular targets and execute a comparative screen of OP neurotoxicity using the asexual freshwater planarian Dugesia japonica, an innovative high-throughput invertebrate system pioneered by the PI. This project will train students in computational image analysis and biostatistics and engage them in hands-on research in modern toxicology.

PROJECT PERIOD: 01/01/2020 – 12/31/2022

Adolescent Mood Project: Efficacy of Counselor-Implemented IPT-AST

Sponsor: U.S. Department of Education
Award Date: 8/25/2019

Project Period: 7/1/2019 – 6/30/2024

Functional Analysis of Locus-Specific Pericentric Satellite Expression

SPONSOR: National Institutes of Health
AWARD DATE: 9/5/2019

The goal of this project is to understand the basic structure and function of specific DNA sequences found near chromosomal centromeres – constricted regions to which spindle fibers attach, enabling duplicated chromosomes to segregate to opposite poles of a dividing cell. Tandemly repeated DNA sequences reside within these regions of chromosomes and have been historically poorly studied due to difficulties in the genomic assembly of repetitive DNA sequences. In cancer cells, these repetitive sequences are misregulated such that they become expressed, and we aim to understand both their sequence diversity and consequences of their expression. The proposed project promises to engage and train undergraduate researchers in innovative genomics, cytological and proteomics techniques, which will propel future careers in genomics and biomedical research.

PROJECT PERIOD: 9/5/2019 - 8/31/2022

Characterization of the interaction of M1 and M2: Influenza A proteins critical to viral assembly

SPONSOR: National Institutes of Health
AWARD DATE: 8/23/2019

The threat of future influenza pandemics, coupled with the growing resistance to current antiviral drugs, makes the development of new influenza drugs a national healthcare priority. This proposal describes experiments designed to provide an atomic-level understanding of how influenza viruses assemble and then bud from infected cells. This structural information could inform efforts to inhibit the replication of viruses, offering a significant potential for a new generation of anti-flu drugs. Undergraduate research students supported by this award will explore an issue of critical public health importance using cutting edge biophysical techniques, participate in established interdisciplinary collaborations, be co-authors on published work and be mentored by experts committed to their long-term career development.

PROJECT PERIOD: 9/1/2019 - 8/31/2022

Dive into Systems - A Free Online Textbook for Introductory Computer Systems Topics

SPONSOR: Special Interest Group on Computer Science
AWARD DATE: 6/29/2019

The purpose of this collaborative project with West Point is to develop and promote a free online textbook that covers introductory computer systems, architecture and parallel computing. The expense of modern textbooks often limits their availability to students and universities that can afford them. As computational thinking and programming increasingly becomes a desired skill-set, cost-effective computing materials are needed to make computer science (CS) accessible to everyone. Our textbook covers topics that are applicable to a wide range of courses, including introductory computer systems, computer organization, C programming, and parallel computing. To the best of our knowledge, this is the first textbook that incorporates all of these concepts and introduces them at an introductory-level, assuming only a CSI background of the reader.

PROJECT PERIOD: 7/1/2019 - 6/30/2020

Collaborative Research: Empirical Models of Supracompetitive Pricing in Differentiated Products Markets

SPONSOR: National Science Foundation
Award Date: 8/17/2018

This project is a collaboration with Georgetown University and the Ohio State University to improve the understanding of market power in differentiated product markets. The researchers will study supra-competitive pricing using a model of price leadership that fits the U.S. beer market, exploring why prices rose more than predicted by current modeling after the Miller/Coors joint venture, why price increases were limited to Anheuser-Busch/Inbev and MillerCoors, and the impact of multi-market contact. The research team will also examine ways to test and quantify cartel collusion by studying evidence from recent price fixing cases within the canned tuna industry.

Project Period: 9/15/2018 - 8/31/2020

Direct and spillover effects of Medicare payment changes on nursing home quality and volume

SPONSor:  Agency for Healthcare Research and Quality (AHRQ)
Award Date:  7/31/2018

Daifeng He will work with research partners at the College of William & Mary to study the causal effects of Medicare payment rates on Skilled Nursing Facility (SNF) volume and quality.  This project will provide evidence about how these subsequent changes will affect SNFs and lay the groundwork for informing policymakers about the effects of the ACA’s productivity adjustments for hospitals and other healthcare facilities.  Importantly, the results will inform legislative debates about state certificate of need laws, state Medicaid payment policy, and federal antitrust regulations.

Project Period:  8/1/2018 – 7/31/2019

Quantification of the Wnt Morphogen Gradient in Hydra and Mechanically Induced Symmetry Breaking

SPonsor:  Gordon and Betty Moore Foundation
Award Date:  05/09/2018

The Wnt/ß-catenin pathway plays an important role for developmental patterning and tissue homeostasis.  Misregulation in Wnt signaling has been linked to numerous diseases in humans, including cancer.  During development, Wnt proteins are secreted and form a concentration gradient that conveys positional information to cells.  This allows Wnt signaling to exert long range effects on tissue patterning and growth, controlling anterior-posterior polarity in a variety of organisms.  Recent technological advances enable us to visualize endogenous Wnt proteins.  This opens the door to quantitative studies of the Wnt gradient during development and allows us to investigate the mutual regulation of mechanically-induced morphological changes and Wnt signaling in axial patterning.  How these mechanical oscillations influence the Wnt gradients and vice versa remains an unsolved question.  We study this mutual regulation in the freshwater cnidarian Hydra and seek to quantitatively dissect the interplay of Wnt gradients and mechanical forcing during symmetry breaking regeneration in Hydra.

Project Period:  05/25/2018 – 10/31/2019

CAREER:  Emergence of Population Diversity from Stem Cell Decision Making in Asexual Planarians

sponsor:  National Science Foundation
Award Date:  3/28/2018

Diversity of individuals is indispensable for population survival and evolution. This project examines how phenotypic diversity can emerge from decision making of individual stem cells in a multicellular regenerative organism. Asexual freshwater planarians are famous for the regenerative capabilities that are based on a large number of adult pluripotent stem cells (ASCs). These ASCs allow them to reproduce by binary fission, thus creating a clonal population and raising the question of how this species is able to create sufficient diversity to survive on evolutionary time scales. Using tools from statistical physics, we recently demonstrated that reproduction is largely stochastic, but that reproductive patterns exist whose molecular and physical determinants remain to be investigated. This proposal aims to test the hypothesis that population diversity arises from a joint effect of the specifics of planarian reproduction mechanics and epigenetic diversity of ASCs in individual worms.

Project Period:  3/1/2018 – 6/30/2021

Unraveling the Role of Mechanics for Tissue Self-organization in Vivo

sponsor:  Research Corporation for Science Advancement
Award Date:  2/6/2018

This project addresses fundamental questions regarding the role of mechanical interactions for pattern formation in development. It has two aims: (1) to determine the role of mechanical properties for cell behaviors during tissue organization and body axis formation and (2) to obtain in vivo measurements of the forces individual cells experience and their connection to cell signaling during these patterning processes. Using a multiscale approach from the molecular to the organismal level, this study will provide insight into how macroscopic organism-level patterning emerges from physicochemical interactions on the microscopic scale.

Project Period:  1/1/2018 – 6/30/2020

Exploring Fixed Costs in Female Hiring:  The Role of Adjustment Costs and Cultural Barriers to Women’s Employment

sponsor:  Harvard Kennedy School
Award Date:  08/22/2017

Saudi Arabia’s Nitaqat program has sharply increased female employment in the private sector.  However, hiring was not spread evenly across firms. Some have shown rapid growth in female employment; others have continued to employ only male workers.  This study will begin studying if this may be due to fixed costs. While hiring female workers may be attractive to firms trying to meet nationalization quotas, firms must first invest in the capacity to hire women. Workplace adjustments may also be needed to comply with cultural norms.  This pilot will gather information on firms’ assessments of these constraints through a combination of administrative data analysis, interviews, and a firm survey. While the focus will be on fixed costs, the evidence gathered as part of this study will likely shed light on the perceived barriers to hiring women, providing crucial evidence for future work on female labor force participation in the region.

Project Period:  6/1/2017 – 8/31/2019

Locus-Specific regulation of pericentric satellite sequences

sponsor:  The Charles E. Kaufman Foundation
Award Date:  7/26/2017

This research project will generate a high-resolution map of specific HSATII sequences within the human genome in order to propel further functional studies to understand the consequence of locus-specific HSATII misregulation in cancer. A full characterization of the level of variation within the HSATII sequence family, an analysis both fundamental and pure, is essential to understanding the regulatory roles of pericentric satellites. This rich resource, and the tools to be developed during the scope of the project, will be of value both within the genomics community, the broader cancer research community, and in the training of our future scientists.

Project Period: 9/1/2017 - 8/31/2019

Equivariant and Combinatorial Algebraic Geometry

sponsor:  The Simons Foundation
Award Date:  1/30/2017

The Simons Foundation has awarded a grant to Dr. Chen to support her research on combinatorial and enumerative problems in algebraic geometry, and fruitful interactions between modern methods in algebraic geometry and new developments in combinatorics, representation theory, symplectic geometry, and other fields. Fundamentally linked to these problems are the study of moduli and parameter spaces and their cohomology theories, and the study of objects that are combinatorially rich in structure.  Her work discusses recent and ongoing work on equivariant and quantam Schubert calculus of homogeneous spaces, brill-Noether theory of curves, K-theory of degeneracy loci, affine Grassmannians, Hessenberg varieties, and generalizations of the moduli space of curves.

Project Period:  9/1/2017 - 8/31/2022

Collaborative Research: Hybrid Professional Development to Enhance Teachers’ Use of Bootstrap

SPonsor:  National Science Foundation
Award Date:  8/23/2017

Bootstrap's current professional development (PD) program for math teachers is a 3-day in-person event which assumes that teachers are somewhat facile with algebraic functions. This project studies how to develop teachers' understanding of CS and strengthens their math proficiency. A total of 270 middle-school math teachers—a majority from rural areas or serving Native American or Hispanic students—will participate in Bootstrap PD under this project. Assuming typical adoption rates, these teachers should reach 6,000 students within the project period alone. Building Bootstrap content into the Math Forum exposes thousands of NCTM's teachers to the potential of integrated math/CS curricula.

Project Period:  9/1/2017 - 8/31/2020

Deciphering the structure and dynamics of quadruplex DNA and DNA-ligand complexes

SPonSor:  National Institutes of Health
Award Date:  3/24/2017

The proposed research will improve the selectivity and efficacy of anticancer therapies by contributing new knowledge about non-canonical G-quadruplex (GQ) DNA structure, and the interactions of GQs with small molecule ligands. GQ DNA has been firmly established as an important therapeutic target for cancer. Unfortunately, DNA-centered drug discovery programs suffer from limited structural information available for GQs, especially in the presence of ligands. To address these challenges, this research will perform comprehensive crystallographic investigations focused on telomeric and oncogene promoter G-quadruplexes. This work will be accompanied by spectroscopic and calorimetric studies of the thermodynamic parameters of ligand binding to GQ DNA (e.g., stoichiometry, affinity, selectivity, driving forces). Kinetic information can help identify the timescale of G-quadruplex formation and thus biological processes that can be affected by the presence of these structures. Collectively, the proposed work will enhance our understanding of GQ structural plasticity, supply coordinates for drug discovery platforms, shed light on the origin of ligand selectivity for a specific DNA target, and guide the design of novel highly selective anticancer therapies while providing transformative training to Swarthmore undergraduate students.

Project Period:  6/1/2017 - 5/31/2020

Mid-Atlantic Algebra, Geometry, and Combinatorics Workshop

SPonsor:  National Science Foundation
Award Date:  2/15/2017

Linda is Co-PI on this collaborative grant to Haverford College that provides support for speakers and participants in the Mid-Atlantic Algebra, Geometry, and Combinatorics (MAAGC) workshop. MAAGC, an annual Philadelphia conference bringing together senior researchers and junior mathematicians, promotes collaborations and regional interactions, while highlighting recent developments in algebra, geometry, and combinatorics. MAAGC workshops bring mathematicians from North America together to discuss advances in algebraic combinatorics, algebraic geometry, representation theory, and other related fields.

Project Period:  3/1/2017 - 2/29/2020

Collaborative Research: Plant and Fungal Diversity of Tafea Province, Vanuatu, a Threatended Hotspot

Sponsor: National Science Foundation
Award Date: 3/29/2016

Vanuatu is a group of 80 islands located in the South Pacific, situated roughly equidistant from New Caledonia, Fiji, and the Solomon Islands, all of which are globally important biodiversity hotspots. Despite its significance as a treasure trove of biodiversity, Vanuatu’s plants and fungi remain poorly documented, rendering it a “biodiversity black hole” and, thus, leaving a significant gap in our knowledge of biogeographic relationships with neighboring island countries. Along with its rich biological diversity, Vanuatu is also the most linguistically dense country in the world, with 112 languages for a total population of only 253,000; nine of these languages are found only in Tafea Province. The researchers will complete the first comprehensive survey of angiosperms, gymnosperms, ferns, lycophytes, bryophytes, endophytic and macro-fungi, and lichens ever undertaken in Tafea Province. Formal student training will also take place at the University of the South Pacific, California State University–East Bay, Swarthmore College, University of Hawai‘i, and the New York Botanical Garden. Because most land in Vanuatu is held under customary ownership, and local people are the stewards of their environments, the loss of biocultural knowledge is a serious threat to their ability to manage biodiversity resources sustainably.

Project Period: 7/1/2016 - 6/30/2021

Plasma Accelerator on the Swarthmore Spheromak Experiment (with Bryn Mawr College)

SPonSor: U.S. Department of Energy, Advanced Research Projects Agency-Energy (ARPA-E)
Award Date: 9/23/2015

David Schaffner (Bryn Mawr) and Michael Brown will design, develop, and test two flexible, low-cost, small-scale plasma acceleration modules for the purpose of injecting energy in the form of high velocity non-axisymmetric magnetized plasma into a fusion chamber at high energy efficiency and high repetition rate. This module will be built onto the existing Swarthmore Spheromak Experiment machine. The ultimate goal of this project is to develop plasma acceleration/energy injection technology that can be used in conjunction with a variety of fusion machines. This project aims to prove the ability to provide significant energy to a fusion plasma system on a small scale, with minimum additional infrastructure.

Project Period: 9/28/2015 - 9/27/2019

REU Site Proposal Building dictionaries to support endangered languages and preserve environmental knowledge in Mexico, Micronesia, and Navajo Nation

Co-PI's: Brook Lillehaugen, Ted Fernald, & Jamie Thomas
sponsor: National Science Foundation
Award Date: 12/5/2014

The project builds bridges between indigenous linguists in the US academic community, Mexico, Micronesia, and the Navajo Nation, with collaborative research that benefits all parties. It helps uncover deep connections between languages and landscapes by documenting the knowledge base about the natural world found in endangered languages. The resulting linguistic materials support local communities' language revitalization efforts. They will also be a resource to the broader scientific community seeking to understand language complexity, diversity and universals. The project begins with a two-week intensive, hands-on training session on current best practice for recording languages (or areas of grammar within languages) that have not yet been adequately documented. Students learn directly from professional linguists and indigenous language experts how endangered languages are being modernized, digitized, and expanded into new technological domains. In weeks three and four, students participate in a two-week field practicum. Working in teams led by indigenous language experts, students help record basic and specialized lexica, folk taxonomies, toponyms, and ethno-biological nomenclature. They explore and help document the rich knowledge base in each language that uniquely encodes the natural environment (flora, fauna, weather, geography, etc.). They also learn current best practices in sustaining indigenous languages and supporting global language diversity.

Project Period: 5/1/2015 - 6/30/2021

Phase II:  Policy Research Engagement, Human Resources Development Fund of the Kingdom of Saudi Arabia and Evidence for Policy Design, Harvard Kennedy School

sponsor: Harvard Kennedy School
Award Date: 7/14/2014

Professor Peck’s expertise is in development and labor issues in resource-rich countries, and some of her recent work focuses on the impact of Saudi labor market policies on the growth of the private sector. Her experience in these areas will help advance the aims of Phase II of this policy/research engagement between the Human Resources Development Fund (HDRF) of the Kingdom of Saudi Arabia and the Evidence for Policy Design (EPoD) program at Harvard Kennedy School. Her contributions to this project include organizing and participating in policy research symposia to review research results and policy developments.
 

Project Period: 11/1/2014 - 10/31/2019