The Charles E. Kaufman Integrated Research and Education Grants (IREG) program is taking a pause in 2023. If you have any questions, please contact us at email@example.com.
William Pfalzgraff, Ph.D.
Assistant Professor of chemistry at Chatham University
Controlling catalytic selectivity with external electric fields
Catalysts are essential because they provide efficient and clean chemical transformations in industries including pharmaceuticals, food production, plastics and energy. The goal of this research is to develop new approaches to optimize catalysts by providing a theoretical framework that explains how one can precisely control the products produced in a chemical reaction using externally applied electric fields. Recent experimental work has shown that yields for reactions in solution can be enhanced by up to two orders of magnitude using external electric fields. The ability to use electric fields in this way provides an opportunity to create a new tool for enhancing synthetic chemistry. However, realizing this vision requires a deeper understanding of the physical mechanisms that underlie this process, such as the interplay between applied fields and reactive molecular species. This research will use theory and simulation to elucidate a recently developed experimental setup for applying fields to reactions in solution. By combining electronic structure with molecular dynamics, researchers will model how different experimental factors, such as solvent, ions and selectivity-determining transition states, contribute to this effect. This will enable researchers to unravel how these give rise to selectivity, and thus to develop design principles for optimizing experiments that exploit external electric fields. This interdisciplinary strategy combines chemistry, physics and materials science and integrates closely with experiment, allowing for insights gained from simulations to be efficiently implemented and tested to develop this evolving area of synthesis. This work will also engage a diverse group of undergraduates in research and provide training in theory, simulation and experiment-theory collaboration. This research will advance fundamental understanding of selectivity in catalysis and has the potential to provide a new method for tuning reactivity in solution.
Michael Roberts, Ph.D.
Associate Professor of biology at Dickinson College
Jeffrey Forrester, Ph.D.
Associate Professor of mathematics at Dickinson College
Reprogramming acute myeloid leukemia cells toward cell cycle arrest and death
Cancer is a group of genetic diseases characterized by the transformation of normal cells into cells that lose their specialized functions, divide continuously and escape the mechanisms of programmed cell death available to normal cells that are damaged. These cancer hallmarks are caused by mutations in a finite number of genes classified as oncogenes (which promote proliferation) and tumor suppressor genes (which inhibit cell division and regulate survival). Cells, in response to external cues that are transduced to the nucleus where gene expression is affected, make reversible proliferation and survival decisions. When signaling systems are corrupted by oncogenic mutations, signaling becomes dysregulated and proceeds even in the absence of the normal upstream cues, causing growth and survival pathways to become “stuck” in the ON position. In the high mortality cancer, acute myeloid leukemia, a commonly mutated gene encoding a growth-signaling protein that becomes hyperactive is called RAS. Oncogenic RAS mutations are responsible for approximately 20% of all human cancers. In this study researchers will exploit the availability of RAS-driven AML cell lines to investigate how hyperactive RAS signaling can be shut down by genetically altering the leukemic program of gene expression. Candidate genes, known to inhibit RAS signaling in normal cells, which are “off” in the AML cells, have been identified and will be introduced into the AML cells. The effects of “overexpressing” these genes will be evaluated by measuring changes in leukemia cell proliferation and death. Overexpressed genes that facilitate the reversal of AML cell characteristics will be further assessed to determine the mechanisms by which they reprogram the leukemia cells toward non-dividing and destructive states. The techniques of AML cell line culturing, gene transfer, gene expression measurement, and proliferation and programmed cell death assessment are well established in the researchers’ laboratory and will be executed by overlapping cohorts of 12 undergraduate students during the funding period. These students will be trained in the state-of-the-art methods and will design and conduct their own experiments during the two academic semesters and summer of the research experience. Additionally, student co-researchers will complete course work in cancer biology and data analytics, positioning them to conduct computational analyses of gene expression data from the cell lines and from large AML patient datasets. This project will generate novel information about genetic strategies for facilitating the reprogramming of RAS-driven cancers leading to proliferative cessation and cell death, while training young scientists through hands-on experimentation and computational data analysis.
Kelly M. Lohr, Ph.D.
Assistant Professor of Biology, Washington & Jefferson College
Environmental exposures and neurodegenerative disease in a drosophila model
Neurodegenerative diseases, including Alzheimer’s disease, are defined by progressive neuronal death that lead to a variety of debilitating symptoms in those affected. Despite growing knowledge of disease-associated genes, the majority of neurodegenerative disease cases are not linked to a single genetic cause. This suggests that “second hits,” such as an environmental exposure or injury, also contribute to these diseases. Our research at Washington & Jefferson College examines such mechanisms in genetic models of neurodegeneration using the fruit fly, Drosophila melanogaster. In the past three years, W&J students have collected preliminary data examining the effects of two disease-modifying factors, the gut microbiome manipulation and traumatic injury. Taking advantage of the power of Drosophila genetics, we use genetic tools and pathological and behavioral assessments to investigate the effects of these factors on neurodegeneration and potential therapeutic pathways. These studies are designed for, and easily completed by, undergraduate biology students within a research internship. Positive outcomes from these studies will be suitable for publication and conference presentation, while also providing valuable, and often difficult to find, undergraduate research experiences for our students as they move forward in their careers.
Patrick Melvin, Ph.D.
Assistant Professor, Chemistry Department, Bryn Mawr College
Improving on Mother Nature: Efficient fluorination of organic molecules using a novel sulfur reagent
Ask any organic chemist and they will tell you that nature’s synthetic prowess still far surpasses what any chemist can achieve in the laboratory. Certainly, most would agree that we still have a great deal to learn from Mother Nature when it comes to stitching together complex organic molecules. However, one area that nature has seemingly neglected is organofluorine chemistry. Still, due to an overwhelming number of positive benefits that fluorine can offer, fluorinated pharmaceuticals have seen exponential growth over the last several decades. But, without a blueprint from nature, organic chemists have been tasked with developing our own methodology for incorporating this incredibly powerful element. The goal of this undergraduate-driven research project is to develop a potent reagent that will facilitate the fluorination of a multitude of organic molecules under conditions that were previously impossible. From a chemistry standpoint, success in this endeavor will not only translate to more efficient syntheses of fluorinated pharmaceuticals but will also lead to a more diverse array of fluorine-containing drug molecules. From an education perspective, the work in this proposal is to be completed entirely by Bryn Mawr College undergraduates, meaning that this Integrated Research-Education Grant will support extensive training of the next generation of women scientists. Upwards of 15 undergraduate students will be supported by this funding, developing specific skills in organic synthesis and methodology while also gaining experience in bringing a project from initial hypothesis to publication.
Kristen E. Whalen, Ph.D.
Assistant Professor of Biology, Haverford College
Elucidating the protective role of bacterial signals in algal host-virus dynamics
A major gap in our understanding of eukaryotic cell biology is the extent to which microbes influence host development and fitness. Microbes are now emerging as critical players in host success, due to their ability to shape the trajectory of eukaryote physiology. In marine systems, chemically mediated interactions between bacteria and their eukaryotic phytoplankton hosts impact the physiology of both partners, alter the chemistry of the environment and shape ecosystem diversity. We previously described how a bacterial quorum sensing signal, 2-heptyl-4-quinolone (HHQ), recognized for its role in microbial cell-to-cell communication in pathogens, disrupts essential DNA replication and repair machinery in a eukaryotic phytoplankton host, thereby inhibiting cell cycle progression and leading to resistance against virus-induced mortality in the model phytoplankton, Emiliania huxleyi. Viral infection and lysis in the ocean leads to the turnover of at least 20% of photosynthetic biomass daily, equating to the release of close to 10 billion tons of carbon per day, underscoring the immense impact viral lysis has on ocean biogeochemistry. Therefore, the ability of HHQ to trigger an immediate response in the eukaryotic phytoplankton host to evade viral death adds a rich new layer of complexity to the viral-host story by presenting evidence that bacteria are capable of chemically interfering with phytoplankton viral lysis. What remains elusive is knowledge of the underlying molecular-level mechanisms responsible for HHQ-initiated protection against viral death. In this integrated research-education grant, undergraduate researchers will use our phytoplankton-virus model in experiments to tease apart how HHQ remodels eukaryote host physiology to promote evasion from viral lysis, ultimately revealing how bacterial signals drive cross-kingdom interactions.
ADDITIONAL GRANTS AWARDED BY THE PITTSBURGH FOUNDATION (2021)
The two grantees below applied to the Integrated-Research and Education Grants program through the Kaufman Foundation and were ranked highly by the Scientific Advisory Board. Due to the availability of additional scientific research funds through The Pittsburgh Foundation and the highly competitive nature of the proposal, these proposals were consequently reviewed by The Pittsburgh Foundation board and approved for funding at the Nov. 17, 2021 Program and Policy Committee meeting.
Ryan Trainor, Ph.D.
Assistant Professor of Physics, Franklin & Marshall College
Galaxy growth and feedback traced by Lyman-Alpha Emission
Galaxies are our primary tools for measuring the evolution of the Universe. While gas, dark matter and dark energy make up most of the Universe, these components are largely invisible and therefore challenging to measure directly. Instead, the light from galaxies–produced both by stars and by energetic material falling into supermassive black holes –must be used to indirectly characterize the large-scale distribution of matter in the Universe, its ionization state and its evolution over cosmic time. For these reasons, it is essential to understand exactly how galaxies and the light they emit trace the structure of the Universe. Furthermore, the properties of these galaxies themselves reveal Earth’s own cosmic history, as their formation includes building up all the elements in the periodic table from primordial hydrogen and helium. Currently, our progress on these compelling topics is impeded by our poor understanding of galaxy feedback: the interactions of stars, gas and supermassive black holes that suppress star formation, disperse heavy elements and inject energy into the material around galaxies. Comparisons of simulations with observed galaxies show that galaxies form fewer stars than their gas could allow–particularly in the lowest-and highest-mass galaxies (e.g., Behroozi et al. 2013)–and feedback from stars and/or black holes is expected to cause this inefficiency. In addition, the effects of feedback shift the observed emission lines(e.g., the Lyman-alpha lineof hydrogen, Lyα) that must be understood for upcoming surveys to characterize the nature and evolution of dark energy(e.g., HETDEX, Hill et al. 2008). Lastly, feedback determines how ionizing ultraviolet photons escape from galaxies, thereby regulating osmic “reionization” (e.g., Robertson et al, 2015): a global phase transition of the entire Universe that also affects the visibility of galaxies. This proposed project will use measurements of Lyα emission a few billion years after the Big Bang to characterize galaxy feedback from both stars and supermassive black holes.
Moria Chambers, Ph.D.
Assistant Professor of Biology, Bucknell University
Assistant Professor of Biology, Bucknell University
Impact of life-stage on immune investment in the common eastern firefly
A key question in biology is how organisms have adapted to maximize their survival and reproduction (fitness) in light of finite energy resources and investing different amounts of energy toward growth, self-maintenance and reproduction. One substantial component of self-maintenance is responding to infection, which uses two overarching strategies: Resistance, meaning killing or constraining pathogen growth, and tolerance, which means minimizing the impact of the pathogen’s presence. Both the infection itself and the response to infection are energetically costly, thus no organism can maximally invest simultaneously in resistance and tolerance throughout its entire life. This project measures resistance and tolerance during infection at the organismal level by simultaneously examining fitness and number of microbes post-infection and at the molecular level by assessing how specific genes associated with resistance or tolerance respond to infection. Despite advances in sequencing technology that enable gene-level assessment of almost any organism in any life stage, the current understanding of resistance and tolerance is limited by work on select species that often focuses on a single life-stage and/or a single perspective. We propose using the common eastern firefly, Photinus pyralis, to test the hypothesis that investment in resistance and tolerance changes over the life of an individual organism, integrating both whole-organism and gene level perspectives, P. pyralis is particularly well-suited for this inquiry as there are extreme differences in the duration of and environment experienced by different life stages. Larvae live for up to two years in and on microbe-rich soil, consuming worms and snails (each with their own microbiota) to fuel robust growth, whereas adults live only for a few weeks where they do not consume any food and are focused entirely on reproduction. Mathematical modeling suggests that long-lived organisms with high exposure to pathogens are likely to prioritize investment in immunity, and we hypothesize life-stages with these traits will also have increased immune investment. Therefore, we predict that firefly larvae will have both high resistance and tolerance to bacterial infections, while adults may prioritize one strategy alone. No matter the result, this project will provide deeper insights into how different life-stages impact investment in resistance and tolerance providing important insight into a fundamental biological question. In addition, it will also inform firefly conservation efforts and enhance discovery of novel antimicrobials by suggesting which life-stages invest more energy in resistance. Importantly, the two PIs will mentor six undergraduate students over the duration of this project as they learn how to capture, care for, and infect fireflies, as well as gene sequencing and analysis. With intentional and compassionate mentoring, students will learn the intricacies of the scientific process and build their identities as researchers.
Mark Ams, Ph.D.
Associate Professor, Department of Chemistry, Allegheny College
Toward creating alien life: a genetic self-replicating system using chalcogen bonds
Can life be created? At the heart of this proposal is the fundamental question of whether life can exist beyond the confines of DNA – the only blueprint for life that humans know. However, the invention of an alternative to DNA, one that is radically different and not based on biotic chemicals (i.e., exobiotic), would represent a seismic shift of our own understanding of DNA’s uniqueness and origins, as well as open the door for entirely new advances in biotechnology. We propose an alternative architecture to DNA, based on the little-known but highly versatile benzochalcogenadiazole (BCD) building block. Our blueprint is designed to carry out the two basic functions of self-replication and genetic encoding, a combination that is unprecedented in current exobiotic designs. Unlike DNA, our design does not require help from enzymes to operate, and thus is engineered to function in the early stages of its evolutionary development. To achieve our goal, we will demonstrate the “proof of concept” that our BCD template can undergo autocatalytic self-replication. Once achieved, our long-term goal is to create an expanded BCD chemical network that allows for competition and natural selection to take hold. Thus, the “big picture” of this proposal is to stimulate molecular evolution, moving us a step closer to realizing a synthetic cell of alien origins. All experiments will be conducted by undergraduate students under the close mentorship of the primary investigator, directly impacting up to 16 undergraduates and ensuring high-quality training for the next generation of research scientists.
ADDITIONAL GRANTS AWARDED BY THE PITTSBURGH FOUNDATION (2020)
The two grantees below applied to the Integrated-Research and Education Grants program through the Kaufman Foundation and were ranked highly by the Scientific Advisory Board. Due to the availability of additional scientific research funds through The Pittsburgh Foundation and the highly competitive nature of the proposal, these proposals were consequently reviewed by The Pittsburgh Foundation board and approved for funding at the Nov. 18, 2020 Program and Policy Committee meeting.
Lisa A. Fredin, Ph.D.
Assistant Professor, Department of Chemistry (Co-PI), Lehigh University
Elizabeth R. Young, Ph.D.
Assistant Professor, Department of Chemistry (Co-PI), Lehigh University.
A new chemical intuition of excited-state reactivity
In order to build a clean energy economy, new photochemically-driven reactions are important for efficient solar energy capture and conversion. While driving reactions with light is less conventional than the typical heating of a beaker, it provides unique opportunities to initiate and control chemical reactions. For the past 50 years, physical chemists, especially spectroscopists and theorists, have built our so-called “chemical intuition” or understanding of how electron and proton transfer reactions occur primarily in the lowest energy states of molecules. However, when driving reactions with light, molecules necessarily become excited. The complex nature of excited states makes them more difficult to predict and understand, and thus we must develop a new chemical intuition for their reactivity. This integrated research-education grant will establish a program for undergraduates to build chemical intuition of light-initiated electron and proton transfer in model azo dyes by combining spectroscopy and quantum mechanics.
Daniela Fera, Ph.D.
Assistant Professor, Department of Chemistry and Biochemistry (PI), Swarthmore College
Dissecting interactions of protein kinases critical to antibody production
Protein kinases act as molecular on/off switches in cells. Their functions vary from controlling cell growth to controlling immune responses. The proposed research will focus on protein kinases that are critical regulators of B cell activation. B cells are the specialized cells that produce antibodies in the human body to protect against foreign antigens, such as viruses or bacteria. The message of a B cell binding to an antigen gets transmitted into the cell, which triggers kinases to turn on other macromolecules, eventually resulting in the proliferation of B cells and the production of antibodies. A detailed atomic picture of the complete molecular pathway involved in this process is not yet available and would be important for understanding how the development of antibodies is regulated. The proposed research will involve performing a molecular “dissection” at one juncture of the pathway using approaches from structural biology, biochemistry, and molecular biology, to understand important kinase interactions and effects on activity. These studies will provide a proof-of-concept for studying other kinase complexes and help us better understand the fundamental principles of antibody production. Such information has implications in understanding how B cells behave in the face of viruses and other pathogens and could pave the way for learning what causes autoimmune disease, i.e. through the production of antibodies that target host macromolecules. Through this work, research and course students will engage in authentic research experiences, gain skills that will help them in future scientific endeavors, and make important contributions to science.
Roberto Ramos, Ph.D.
Associate Professor, Department of Physics, University of the Sciences
Undergraduates Investigating Quantum Effects In Multi-Gap Superconductivity In Novel Superconductors
The goal of this proposal is to enable undergraduate physics students to investigate the superconducting energy gap structure of quantum materials, particularly the recently- discovered iron-based superconductors and their resulting quantum properties, as measured using high- resolution tunneling spectroscopy at low to very low temperatures. Iron-based superconductors provide a new and natural platform where multi-band superconductivity can be studied. Multiple energy gaps in these samples can be measured, depending on the way the crystal has been grown and how the tunneling directions are accessed through fabrication and the way electrical contacts are made. These energy gaps exhibit anisotropy relative to the crystal lattice, with gaps sensitive to tunneling that is parallel or perpendicular to the c-axis of the lattice. The PI and his all-undergraduate research team have access to crystal samples from some of the world’s leading groups that fabricate high-quality samples of K-doped Ba(1-x)KxFe2As2, Co-doped and P-doped BaFe2As2. Physics majors in his group have developed a method of soft-point-contact spectroscopy that builds on crystals contacted using gold wires and silver paint – making these measurements accessible to undergraduates. By reducing thermal broadening and thermal noise using a cryo-cooler with a base temperature of 2 Kelvin and a wet helium cryostat with a based temperature of 0.3K, an all-undergraduate research team with access to world-class samples will perform some of the highest resolution measurements of the energy gap of these quantum materials. These measurements differ from prior measurements of the group made on conventional BCS superconductors such as MgB2 (magnesium diboride) which has demonstrated multi-gap behavior. Beyond energy gap measurements, the undergraduate team will perform new low-temperature, microwave studies designed to probe the quantum nature of these materials. The method is known as microwave resonant activation which is a way of exploring superconducting Josephson effects in these materials – an area which has not yet been well studied for multi-gap materials. Th is of great interest to the community because it can shed light on the potential of using pnictides for quantum measurements. Furthermore, because of the presence of multiple energy gaps in the material, the team can compare their results with pnictides with prior results using MgB2. In these prior measurements, the PI and collaborating students had performed the first measurements of microwave resonant activation, saw signatures of macroscopic quantum tunneling and escapes from the superconducting state with a quality factor Q comparable to the first qubits.
Because the physics program at USciences is purely undergraduate, this proposal promises to impact in a profound way the research and education of physics majors at the institution by providing undergraduates access to frontier research using world-class samples, training in ultra-low temperature physics and high- vacuum systems, microwave engineering, low-noise conductance measurements, data acquisition and analysis, modeling density of states of multi-gap materials and escapes from the superconducting state, and scientific communication of their results. Students will participate in research conferences to present their research. Undergraduates will be trained and integrated to an all-undergraduate cohort system with a meaningful research and education program. Students will have the chance to travel to collaborator laboratories to take part in fabrication experiences. This program will emphasize several components, including (a) a system of maintaining and updating a daily research notebook; (b) a mentoring system that includes a daily briefing at the beginning and at the end of the day and centered about the research notebook; (c) junior mentorship of younger undergraduates with built-in-accountability; (d) giving regular research seminars and (e) training workshops in scientific communication – in particular, training undergraduates to give compelling elevator talks in both specialist and non-specialist language, crafting effective abstracts and research posters, and acquiring skills in extended research-storytelling. Using these skills, they will help organize an annual mini-research workshop centered on these “best-practices”, and which will be open to STEM undergraduates from both USciences and area colleges, for maximum impact. They will be required to participate in existing research activities organized by USciences’ Center for Undergraduate Research. Finally, the program will be assessed through yearly interviews and mid-year blind surveys.
ADDITIONAL GRANTS AWARDED BY THE PITTSBURGH FOUNDATION (2018)
The two grantees below applied to the Integrated-Research and Education Grants program through the Kaufman foundation and were ranked highly by the Scientific Advisory Board. Due to the availability of additional scientific research funds through The Pittsburgh Foundation and the highly competitive nature of the proposal, this proposal was consequently reviewed by The Pittsburgh Foundation board.
Margaret M.P. Pearce, Ph.D.
Assistant Professor of Biology and Neuroscience, University of the Sciences
Elucidating phagocytic glial responses to protein aggregation in neurons
Phagocytosis is a fundamental cellular process required for survival of many single-celled eukaryotes, and in multicellular organisms, is responsible for clearing extracellular pathogens or debris. Professional phagocytes in the immune system (e.g., macrophages and neutrophils) and the nervous system (e.g., astrocytes and microglia) eliminate invading microorganisms, dead or dying cells, or other harmful particles by first recognizing and migrating toward chemical “eat me” signals, upregulating expression of phagocytic genes, and then engulfing the debris and sending it to the lysosome for degradation. Phagocytic engulfment is initiated by cell surface receptors that trigger cytoskeletal arrangement and internalization of extracellular material within an intracellular vesicle known as a phagosome. Nascent phagosomes mature through a series of fusion events with endosomes and lysosomes, culminating with degradation of the vesicle contents in the lysosome. However, many bacterial and viral pathogens have evolved mechanisms for co-opting the phagolysosomal pathway to gain access to a host cell’s cytoplasm. Likewise, various disease states are characterized by defective phagocytosis, leading to accumulation of noxious debris inside and outside cells. Various pieces of evidence suggest that leakage of phagosomal contents might also occur under physiological conditions. We have recently developed a Drosophila melanogaster (fruit fly) model of neurodegenerative disease that shows that pathogenic protein aggregates within neurons are recognized and engulfed by phagocytic glia. Surprisingly, a portion of these neuronal aggregates escape from the phagolysosomal system and reach the glial cytoplasm. This experimental model provides a powerful tool for identifying new components of the glial phagocytic pathway, for determining which steps that are susceptible to phagosomal leakage, and for assessing changes in glial gene expression profiles when protein aggregates are present in neurons. The studies described here will engage undergraduate students in a candidate-based screen for phagocytic genes and cell type-specific global changes in protein-coding genes using sophisticated tools available in Drosophila. The students will be exposed to classic fly genetic techniques and cutting-edge high resolution imaging and sequencing techniques (RNAseq) to identify new mechanisms that regulate membrane integrity during phagocytosis and glial transcriptional responses to protein aggregation in neurons.
Véronique A. Delesalle, Ph.D.
Professor of Biology Department of Biology, Gettysburg College
What genetic and ecological factors determine the evolutionary path of viral pathogens as they adapt to their bacterial hosts?
The interactions between bacteriophages (phages for short), viruses that “eat” bacteria, and their bacterial hosts are both interesting in their own right and provide model systems to study host- pathogen interactions. Phages are the most numerous entities in the biosphere with an estimated population size of 1031. They have been implicated in the evolution of bacteria, including their acquisition of virulence, the control of bacterial population densities, the structuring of bacterial communities, as well as in biogeochemical cycling. In the face of increasing antibiotic resistance in bacteria, phage therapy has been proposed as an alternative to control bacterial pathogens (as in the enemy of my enemy is my friend). However, while phage-based solutions to control bacteria in food processing settings have reached the commercial stage, regulatory concerns and uncertainties about treatments using live viruses with unknown evolutionary potential complicate extending phage therapy to human medicine (unless you live in parts of the old Soviet Union).
For practical and theoretical reasons, we need a better understanding of how phages adapt to both “known” and novel hosts. Phages vary in the collection of bacterial strains they can infect; some phages are generalists, others are specialists. Building upon current work in our lab, we will address the following questions: Do specialists and generalists differ in their ability to adapt to their hosts? Does it matter whether the host is susceptible to phages (attacked by more phages) or resistant (attacked by fewer phages)? Does it matter if the bacterial host has adapted to the homogeneous conditions of a lab environment or not? Do lab-adapted phages differ in their ability to adapt compared to “wild” phages? Ultimately, we want to gain an understanding of the condition that allows phages to jump to new hosts. Can genetic or ecological factors predict when host jumps are more likely? These questions require multidisciplinary tools to be answered but can be addressed by undergraduates in the context of summer and/or course-based research experiences and are attractive to students with interests ranging from biochemistry, ecology to human health.