University Of Nebraska Lincoln

NSF Awards · FY 2024 · 2024-09

Electrons have the fundamental property of “spin,” which is analogous to that of a spinning top, and is associated with their angular momentum. This project studies collisions between polarized electrons, which have their spins aligned in one direction, and chiral, or “handed” molecules. Such molecules, of which DNA is an example, are characterized by a spiral, or helical geometry. These experiments address physics questions about the dynamics of electron-chiral molecule scattering, particularly with regard to the magnetic effects caused by the electron spins. They will also provide important clues about the origins of biological homochirality – the fact that all naturally-occurring DNA spirals in the same direction. A source of polarized electrons called a rubidium spin filter is being used in this work; it has the advantage that it is insensitive to the contamination by chiral target molecules that has plagued earlier experiments using polarized electron sources based on photoemission from GaAs. Molecules of hydrogen (that are not chiral) are also being studied. Hydrogen is the simplest molecule, but its interaction with very slow electrons is poorly understood. This project will use very slow electrons that have very well-defined energy and that are spin polarized to provide stringent tests of theory calculations that consider spin-dependent effects in such fundamental collisions. Improved sources of polarized electrons are also being developed that use multiphoton ionization of sharp metallic tips or chiral metallic nanostructures to give the photoemitted electrons a preferential spin direction. This research on polarized electron technology holds the promise of providing new high resolution analytical tools that can be used for biological and materials research, and for industry. The experiments involving collisions between polarized electrons and chiral molecules will extend previous work that showed chiral effects with halocamphor targets. The goal is to now demonstrate such effects in molecules that have biological significance, such as selenocysteine, and to study the effect of the maximum target nuclear charge and location of the target’s chiral center on chiral scattering asymmetries. The scattering of electrons by simple atoms is well understood, but the theory for electron scattering by even the simplest molecules such as H2 is in its infancy, especially when one considers processes involving electronic excitation. The H2 experiments will focus on the energy region just above the excitation threshold for specific processes, where the theory is particularly difficult, because the excited molecule and the receding electron, which has almost no energy, interact strongly for a long time. These studies will rigorously test new theories being developed for such collisions. Ideas for novel sources of polarized electrons based on multiphoton ionization of metallic nanotips and chiral structures will be studied. The goal of this work is to make pulses of electrons that are “fast,” i.e., that have a duration comparable to that of the light pulses producing them, so they can time-resolve processes such as chemical reactions and magnetic wave motion in solids. Experiments will be done to learn if current-carrying nanostructures of tungsten can produce polarized electrons when struck by short light pulses. This work, based on the spin Hall effect, will provide a bridge between the field of spintronics and the production of free polarized electron beams. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

This project will foster a network of collaborators, the Prismatic Community of Practice, to advance knowledge about ethical and responsible human subjects research with a focus on minoritized individuals and communities in science, technology, engineering and mathematics (STEM). All research involving human participants necessarily includes people with, or requires considerations of, minoritized identities. The project focuses specifically on assembling STEM education researchers, education practitioners, educational professional societies, and Institutional Review Board (IRB) personnel to form a community of practice to understand pertinent ethical issues. It will lead to the creation and piloting of a professional development module. The project will have far-reaching benefits by supporting professional development, the progress of social science methodology, and ethical STEM education research. The project will expand knowledge about ethical and responsible human subjects research with a focus on minoritized individuals and communities in STEM. There are many ethical considerations in such research, from research design and confidentiality to participant recruitment, instrumentation, data collection, data storage, data analysis, and the sharing of findings. The project will foster new collaborations and build a community of practice with STEM education researchers, practitioners, professional societies, and personnel from IRB offices. The community of practice will link research and minoritized identities to move the STEM education research field forward in ethical, responsible, and inclusive ways. Project activities will involve developing a pilot module with the community of practice and providing mentoring for postdoctoral fellows and graduate students as part of their involvement in conducting research. In the long run, project activities will provide benefits to education researchers at-large and research participants through a refined module. This project is jointly funded through the ER2 program by the Directorate for Social, Behavioral and Economic Sciences and the Directorate for Mathematical and Physical Sciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Facilitating Constructive Engineering Talk (FACET) is a collaboration between the University of Nebraska Lincoln 4-H and the Tufts University Center for Engineering Education and Outreach. The researchers are studying educators’ talk within 4-H facilitated engineering design activities. Talk moves are a tool that educators can use to elicit learners’ engineering reasoning and sensemaking, encourage explorative learning, and support productive participation in engineering design. This study is using video observations and interviews to understand Nebraska 4-H Educators’ verbal interactions with small teams of rural eight- to twelve-year-old youth and the ways those interactions influence youths’ engineering participation and learning. The project will advance understanding of informal engineering education by exploring 1) pedagogical talk moves that 4-H Educators use to scaffold engineering learning by rural youths, 2) youths’ responses to educators’ talk, and 3) shifts in educators’ teaching as they co-create and participate in professional development. Ultimately, this work will lead to increased participation in engineering study by rural youth, which will lead to a more diverse engineering workforce. In every rural county of Nebraska, 4-H Educators facilitate out-of-school, choice-based, informal engineering learning in 4-H Clubs, libraries, and afterschool programs. 4-H Educators live in or near the communities they serve, closely know local families, and are well-positioned to facilitate culturally relevant engineering learning activities with local youth. Over four years, 4-H Educators and university researchers are collaborating to 1) observe and video record educators and youth engaging in researcher- and educator-developed engineering design activities, 2) interview educators and youth about these engineering teaching and learning experiences, and 3) co-create professional development resources for informal educators. Ultimately, the project will identify Educators’ talk move repertoires, develop understanding of connections between talk moves and youths’ subsequent engineering participation, and co-create and disseminate talk move-focused professional development resources to informal engineering educators. Products from this project include professional development workshops and free, online resources that support informal educators to learn and use talk moves to support youth in participating in and learning engineering. This Integrating Research and Practice project is jointly funded by the Advancing Informal STEM Learning (AISL) program and the Established Program to Stimulate Competitive Research (EPSCoR). AISL seeks to advance new approaches to, and evidence-based understanding of, the design and development of STEM learning in informal environments. This includes providing multiple pathways for broadening access to and engagement in STEM learning experiences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

With more than half of the US electricity consumption due to electrical motors, even small gains in efficiency, especially of the emerging direct current (DC) motors, would have a profound impact on energy usage. Permanent magnets are the most essential component in DC motors, and rare earth permanent magnets are far superior to any other permanent magnet. But since supply chain issues beset rare earth materials, more efficient use of these natural resources is paramount. Additive manufacturing (AM) offers the ability to produce near-net-shape and net-shape parts, significantly decreasing waste of these materials. Additionally, AM provides unique design strategies which can revolutionize motor design, further enhancing performance. More pertinently, AM processes for magnetic materials have not received much attention. This NSF-MeitY award is an international collaboration with the Ministry of Electronics and Information Technology of India (MeitY). It supports research that seeks to understand crucial phenomena, namely, the material solidification and development of microstructure in the AM process for rare earth permanent magnets, which critically affect the magnetic performance. This project will achieve a comprehensive understanding of the additive manufacturing (AM) of rare earth permanent magnets through three main objectives: (1) designing alloys tailored for the solidification conditions encountered during AM; (2) conducting in situ studies of the AM process to gain insights into the processing science of complex alloy systems; and (3) fabricating part-level magnets using commercial laser powder bed fusion machines, producing both isotropic and anisotropic grain structures, from the knowledge gained in Objectives 1 and 2. The results of the project will lead to a thorough understanding of the thermokinetics of the AM process, and from that detailed processing maps to enable exact microstructural design during AM. This project will involve student and faculty exchanges between the University of Nebraska-Lincoln and the India Institute of Technology-Kharagpur, and train students in magnetic materials and AM to ensure continued US leadership in these areas. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This award funds the research activities of Professor Peisi Huang at the University of Nebraska-Lincoln. There has never been a more exciting time for particle physics and cosmology. Ongoing and forthcoming experimental efforts are transforming our understanding of fundamental physics. Despite the remarkable success of modern physics, many mysteries of the Universe suggest there is an entire realm of “new physics” that lies beyond our current understanding. Professor Huang's research aims to utilize current and future experimental probes to advance our understanding of new physics through theoretical studies. Specifically, Professor Huang will study black holes, the imbalance between matter and antimatter, and possible changes in the history of the Universe. As such, Professor Huang's research advances the national interest by promoting the progress of science in one of its most fundamental directions: the discovery and understanding of new physical laws. This project is also envisioned to have significant broader impacts. The proposed research will provide training opportunities for a diverse group of graduate and undergraduate students. Professor Huang also aims to increase participation in STEM by making a special effort to involve women, other underrepresented minorities, and first-generation college students. More technically, Professor Huang will first propose new formation mechanisms and probes for primordial black holes, which are hypothetical black holes formed right after the Big Bang. She will study formation mechanisms through first-order phase transitions. Second, Professor Huang will investigate the imbalance between matter and antimatter by suggesting possible mechanisms, such as models with sub-GeV singlets, that could have created this imbalance and identifying ways to test these theories experimentally. Third, Professor Huang will study potential modifications to the history of the Universe and their implications, including the role of dark matter, though a novel scenario where a dark sector particle couples to a scalar undergoing a strong first-order PT through higher-dimensional operators. This might lead to periods of so-called “early matter domination”. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

In an increasingly global and diverse society, engineering programs are called to produce engineers at all levels who have intercultural competency (also known as global competencies), representing the ability to work with stakeholders across the world and from a variety of cultural backgrounds. These competencies will only become more important, highlighted by the United Nations Sustainable Development Goals, the European Union’s OCED calls to global action to fight global challenges, and the National Academies’ Grand Challenges for Engineering, which innately require global collaboration. Ph.D.- and Master’s educated engineers are thought-leaders who will be at the forefront of developing the technologies that will lead to water sustainability, sustainable energy, and climate solutions, which are inherently global problems. However, intercultural competency research rarely extends to engineering graduate student populations. Current statistics indicate over 50% of engineering graduate students in the United States are international, yet very little intercultural competency training, education, or research is conducted for graduate students. Future Ph.D.-holders, regardless of occupational trajectory or citizenship status, must be equipped to be thought leaders to tackle global challenges like climate change in an increasingly global engineering economy. To meet this need, the purpose of this project is to investigate how graduate engineering students develop intercultural competencies “in the wild” in authentic academic research laboratory environments. Given that over 58% of engineering doctoral students across U.S. institutions are international, the research laboratory becomes a place that, if harnessed, could facilitate intercultural competency development for both U.S. and international students as future thought-leaders. This project is well-aligned with the NSF Research in the Formation of Engineers program in that it focuses on the development of critical competencies for the next generation workforce. Informed by Deardorff’s process model of intercultural competence and theories of graduate socialization, this project will answer the following research questions: What are the current levels of intercultural competency in graduate engineering students and faculty research supervisors at R1 institutions in the United States? What factors augment or inhibit the development of intercultural competencies in engineering graduate students in research lab contexts? How do graduate engineering students develop intercultural competencies in research laboratories over time? To answer these questions, researchers at Penn State and University of Nebraska-Lincoln will collaborate on a two-phase multiple methods project comprising a nationwide benchmarking phase to provide contextual details on the climate impacting graduate student development of intercultural competencies from both the faculty and student perspectives and follow-up deep interview and longitudinal mixed methods phase to understand the development of intercultural competencies over time. Findings from this research will transform both the graduate engineering education research subdiscipline and the global engineering education subdiscipline, which rarely interact. This study will offer the inaugural understanding of how intercultural competencies are fostered or limited as a function of graduate engineering research groups over time. The combination of qualitative and quantitative data will add substantial value to the development of models and future theories for how intercultural competency development may occur “in the wild” as a function of routine laboratory environments. Insights will be translated through the broader impacts activities to hundreds of our own institutions’ departments annually through graduate colloquium series and the development of graduate intercultural competency self-audit toolkits developed as part of this grant. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

The project aims to serve the national interest by developing and researching improved teaching strategies to support students in using science knowledge and skills for science civic engagement. The hope of educators, policymakers, and researchers is that with increased STEM learning, a better informed and skilled citizenry will be more fully engaged and make important decisions to shape and advance our society. Despite the value placed on developing students’ science civic engagement, few classroom models exist to support students’ science civic engagement (especially at an undergraduate level). The significance of this project is to fill this gap by developing an evidence-based classroom model to support students’ science civic engagement, especially focused on experiential learning activities. Much of the learning that helps students connect everyday importance to science knowledge and skills occurs in activities outside of the classroom, which may have unequal access for historically underserved populations, or in upper-division courses after attrition from STEM has already occurred. Incorporating civic engagement into introductory college courses provides an opportunity to support all students in developing science literacy skills, connecting science course content to desired societal outcomes, and to motivate and retain students in STEM career trajectories. This project intends to advance an understanding of how science education can empower students to employ their knowledge and skills to solve complex societal issues. The goals of this project will develop instructional strategies to incorporate experiential learning and civic engagement learning in a large-enrollment STEM course and evaluate the impact of the instructional strategies on students’ development of science literacy skills and science civic engagement. This project is grounded in science education theory and research and aims to perform basic and applied research using qualitative and quantitative data. The research will take place in a large enrollment required introductory science literacy course that serves approximately 600 students every academic year. The science literacy course learning objectives are centered on evaluating, synthesizing and applying relevant scientific evidence to societal decision-making and using both scientific information and values-based objectives to support a position about what should be done about a socioscientific issue (defined as a societal issue that is informed by science). In the course student teams create a dynamic and well-researched project about a complex socioscientific issue and develop recommendations for a solution using a structured decision-making process. Students will be asked to spend a total of 4-6 hours on experiential learning related to their final topic by connecting with a community partner engaged in their topic. Experiential learning in the course may include service learning, data collection or citizen science, direct science civic engagement such as attending a town council meeting, or formal and informal public educational activities. The project aims to address three research questions: (1) Does an experiential learning requirement in an introductory science literacy course, coupled with more explicit instructional guidance on how to civically engage, impact students’ ideas about using their own skills and knowledge to civically engage in their communities? (2) How do students relate their ideas about using their own skills and knowledge to civically engage in their communities to experiential learning activities they performed in an introductory science literacy course? (3) How do students’ ideas about using their own skills and knowledge to civically engage in their communities vary by issues context? Evidence-based transportable teaching program elements to implement experiential learning in large introductory STEM classrooms will be disseminated through workshops, online guides and publications. The NSF IUSE: EDU Program supports research and development projects to improve the effectiveness of STEM education for all students. Through the Engaged Student Learning track, the program supports the creation, exploration, and implementation of promising practices and tools. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

Flash droughts are characterized by the sudden onset and rapid intensification of drought conditions. Large-scale atmospheric and oceanic patterns are well-known to set the stage for drought, but land-atmosphere interactions can play an important role in exacerbating those conditions. This research seeks to understand the role of land surface feedback in flash drought development and explain how flash drought is distinguished from conventional drought through rapid intensification. These events can have substantial agricultural and economic consequences. This award will produce research that may contribute to improved forecasting of flash droughts at the subseasonal and seasonal scales. The project also includes the promotion of science literacy and training of multiple students. The overarching science question of this project is: What is the role of the land surface (soil moisture and vegetation) in modulating flash drought development in the contiguous United States? The research team hypothesizes that: 1) Atmospheric synoptic conditions play a major role in conventional droughts, but land atmosphere interactions can accelerate the drought intensification, leading to flash droughts, and 2) Impacts of land-atmosphere interactions on flash drought occur at both local and mesoscale through drought self-intensification and drought self-propagation, respectively. To address these hypotheses, the PIs plan to characterize flash droughts in the past several decades using multiple drought indicators, investigate the role of atmospheric conditions and land-surface feedback in flash drought development, evaluate flash droughts in an existing 40-year regional climate hindcast, and explore land-atmosphere interactions in new numerical modeling runs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

Plants are affected by diseases caused by diverse groups of microorganisms. When those diseases affect crops, such as rice, they have an enormous negative impact on farmers and food security for a growing human population. A common method to control crop diseases is with synthetic chemical pesticides that can have adverse effects on ecosystems and on human and animal health. An alternative approach involves the use of beneficial microorganisms present in natural environments to counteract the activity of plant pathogens through the production of a variety of molecules known as antimicrobials. A prominent group of environmental bacteria that could be exploited to control plant pathogens are called Pseudomonas; within that group Pseudomonas protegens PBL3 has been effective inhibiting the growth of a plant pathogenic bacterium causing a devastating disease in rice. However, it is not known how P. protegens PBL3 inhibits the growth of the pathogen. Thus, the goal of this project is to identify the specific antimicrobial molecules that P. protegens PBL3 produces and to understand how they inhibit the growth of the pathogen. The results from this project will contribute to developing biologically based solutions to control diseases in crops to reduce crop losses and reduce their economic impact to farmers, while alleviating food insecurity worldwide. In addition, the project will also be used as a platform to provide broad scientific training to emerging scientists at different stages of their careers. Rice is a staple food for more than three billion people worldwide. Rice production is threatened by Bacterial Panicle Blight (BPB) caused by Burkholderia glumae. The absence of completely resistant rice varieties or effective chemical methods to eliminate the pathogen, has paved the way to harness environmental bacteria as sources of effective antimicrobials to control B. glumae. Previously, the environmental bacterium Pseudomonas protegens PBL3 was identified as an antagonistic bacterium against B. glumae, due to antimicrobial molecules that P. protegens PBL3 produces and secretes. However, the specific antimicrobial molecules and their mode of action on B. glumae are unknown. Thus, the proposed project combines multi-disciplinary approaches involving genetics, comparative genomics, metabolomics, and transcriptomics tools to identify genes and pathways in P. protegens PBL3 encoding antimicrobials, elucidate the chemical composition and structure of those antimicrobials and define their mode of action against B. glumae. The project will provide scientific training and professional development activities for a postdoctoral research associate, and a graduate student directly involved with the project. In addition, an important goal of the project is to provide a foundational online course, as well as a hands-on summer research experience to undergraduate students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

Nontechnical Description Ferroelectric materials have a spontaneous electric polarization that can be reversed by the application of an external electric field. They have many applications in electronic devices, such as non-volatile memories, optical filters and pressure sensors. All ferroelectrics are also piezoelectric. They change shape under an applied electric field and can also convert mechanical stress to electrical energy. Hafnia oxide ferroelectrics are unique in that their piezoelectric behavior depends on how they are made and the electrical cycling history. While these are interesting materials, the body of knowledge about hafnia piezoelectricity is largely empirical. The community lacks a fundamental understanding of precisely how such factors determine the piezoelectric properties. This project directly addresses that gap in knowledge. It brings together an interdisciplinary team to perform systematic experimental studies and theoretical modeling of the piezoelectric behavior of hafnia films with controlled microstructure. The ultimate aim is to achieve tunability of the piezoelectric response of hafnia. This in turn will enable design of the devices with enhanced electromechanical performance. The international nature of this project enhances the research, education, and outreach missions of the University of Nebraska and the Luxembourg Institute of Science and Technology. The project prioritizes an increase in the number, quality, and diversity of students pursuing careers in science and technology. Outreach activities to promote science literacy will help to build a culturally diverse community of scientists and educators and enrich their professional preparation and education experience. Technical Description Hafnia-based ferroelectrics are among the most actively studied groups of materials due to the vast range of fundamentally and technologically captivating properties. One of the most intriguing and unique characteristics of these materials is extremely high sensitivity of their piezoelectric properties on a variety of extrinsic factors, which causes a significant discrepancy between the theoretically predicted piezoelectric behavior and broad variations of the experimentally measured parameters. The current international collaborative project seeks to address this outstanding controversy by achieving a fundamental understanding and deterministic control of the piezoelectric properties of the hafnia-based ferroelectrics by adopting an approach based on synergy between theoretical modeling and systematic testing of the role of the intrinsic and extrinsic factors in the piezoelectric behavior. Experimental studies carried out both at the nanoscale and global levels using a combination of the local probe microscopy and time-resolved synchrotron measurements focus on investigation of the ferroelectric and electromechanical properties of the epitaxial, polycrystalline, and free-standing hafnia thin film capacitors as a function of thickness, composition, substrate and film microstructure as well as on evaluation of the effect of electrical cycling and mechanical strain modulation on evolution and tunability of the electromechanical properties. Theoretical studies involve first-principles modeling of the electromechanical response of thin films and free-standing membranes with the goal to assess a role of the intrinsic and extrinsic factors in piezoelectric tunability and provide guidance for the experimental studies. The project is performed in collaboration with the Luxembourg Institute of Science & Technology supported by the Luxembourg National Research Fund. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This project is jointly funded by the Established Program to Stimulate Competitive Research (EPSCoR), and funds allocated to Clean Energy Technology Initiative investments. This Research Advanced by Interdisciplinary Science and Engineering (RAISE) award is made in response to Dear Colleague Letter 23-109, as part of the NSF-wide Clean Energy Technology initiative. Geological processes in the earth's crust create underground deposits of hydrogen gas, which could be a major untapped clean energy resource for the U.S. and the world. However, little is known about how this hydrogen is produced, how it migrates, and whether it accumulates in big enough deposits to be used for clean energy. Because hydrogen is a gas, it escapes the subsurface with ease and does not accumulate underground in the exact same way as water and petroleum, which are far better understood. It also reacts chemically with rocks, soil, and water, and it can be consumed or created by bacteria. The team will conduct a multi-pronged study to better understand subsurface hydrogen in Nebraska, at locations where geologic hydrogen has been found in the past. They will collect water, soil, and rock samples, perform laboratory tests on these materials, and do calculations to better understand how hydrogen moves through the subsurface; and how effectively it can be stored underground. The team will also use DNA testing to identify bacteria in subsurface materials; and will perform calculations based on physics, chemistry, and biology to see whether these bacteria promote or hinder hydrogen storage, and whether they cause hydrogen to be lost as it migrates underground. Outcomes from this project will help with discovery, assessment, and use of naturally occurring hydrogen in Nebraska and elsewhere in the world. Furthermore, a better understanding of fundamental processes along with preliminary evaluations of the natural H2 potential will be coupled with future field-based research and the development of large-scale hydrogen hub projects associated with the research team’s jurisdiction. In addition to the research, the proposed study will contribute to enhancing the education capacity at the University of Nebraska-Lincoln via several proposed activities. The underlying central hypothesis of this project is that specific geomechanical and biogeochemical conditions exist limiting the loss and consumption of naturally generated H2, which in turn, can lead to geologically trapped H2 at an economically meaningful scale in the mid-continent subsurface. The overall objective of this study is to advance understanding of geological hydrogen (natural and engineered systems) in the midcontinent deep subsurface to understand both biological and abiotic processes that contribute to seepage, trapping, and production or loss. To achieve the overall objective, the scope of the research objectives is as follows: (1) Elucidate the transport and accumulation of natural hydrogen in soils and rocks via laboratory tests and field monitoring at the study site near the Midcontinent Rift (in Nebraska), (2) Identify geochemistry of the subsurface fluids and minerals that can support microbial life including hydrogenotrophs, living in the deep subsurface environment, and (3) Integrate two salient phenomena, hydrogen transport and abiotic/biotic reactions, to upscale the study via numerical modeling. In doing so, the project will yield understanding of the flow and interaction of geologic hydrogen with surroundings via the combined efforts of laboratory tests, numerical studies, and field monitoring, and thus will test the project’s central hypothesis. Eventually, this study will establish a strong foundation to make predictions about sources of natural H2, and thus achieve the long-term goal of producing natural H2 at economically viable scales from the Midcontinent Rift system in the USA. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

This project aims to develop artificial Intelligence (AI)-powered approaches to address the real-world challenge of improving accessibility to public facilities (e.g., hospitals, schools, transit stations). The 2022 U.S. Bipartisan Infrastructure Law called for the construction of new roads, bridges, multi-use paths, and mass transit to improve transportation accessibility to public facilities for underserved communities to provide an equitable future. These improvements translate to access to services such as lighting/heating/cooling, education, human connection, healthcare, and jobs. These initiatives pose an inherently challenging question on equitable access and services: how to maximize services for underserved populations to critical public facilities. This problem is known in the literature as the facility accessibility improvement problem (FAIP) which aims to structurally modify a given region (e.g., adding new links) to improve the accessibility of targeted populations to a facility. Existing FAIP models and approaches have several limitations, preventing their direct applications to address these societal challenges on a large scale. Current modeling limitations include: (1) the inability to consider more than one facility in the analysis; (2) not explicitly considering underserved communities’ preferences on the facilities; and, (3) not accounting for disruptions to the region (e.g., transportation network) due to natural disasters or planned construction. The overarching goal of this project is to establish theoretical and algorithmic foundations for the development of scalable and efficient AI-powered approaches to tackle large-scale FAIPs. In the long term, this project will contribute to the well-being of individuals and increase the vitality of communities due to improved access to resources and services. This project will develop AI-powered frameworks and approaches to address the aforementioned societal challenges and overcome current modeling limitations. The project will be carried out through three interconnected thrusts. Thrust 1 will provide collective decision-making FAIP frameworks that consider agent preferences for multiple facilities and efficient and scalable AI-powered approaches based on well-studied accessibility/agent preference models and algorithmic approaches in operations research and AI. Thrust 2 will provide efficient and scalable AI-powered mechanisms based on the Nobel-winning game theory/mechanism design theories for modeling strategic aspects of agents in related problems. Thrust 3 will investigate collective decision-making for FAIPs with disruptions (e.g., partially functional infrastructures) to develop new modeling and AI-powered approaches to maintain existing or improve accessibility, building on Thrusts 1-2, taking into account population priorities and maintaining network properties. To ensure the research products are useful and practical, in the application part of the project, the research team will conduct tabletop exercises with decision-makers (transportation planners and emergency management personnel) and stakeholders (community leaders, including those of underserved communities) to elicit their preferences on various scenarios. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

Understanding the molecular-level details of how cells communicate with each other provides critical insight into how living systems perform complex functions such as regulating metabolism, responding to stress, or learning. Naturally occurring peptides (e.g., neuropeptides and peptide hormones) are molecules which can act as messages to facilitate communication between cells in living systems. After being produced in the cell, most peptides undergo numerous molecular modifications that greatly impact their function. Despite their importance in biology, much about how peptides function, including the roles of their molecular modifications, are not well understood. This project will investigate the roles of an understudied modification that occurs in some peptides called amino acid isomerization, which generates molecules called D-amino acid-containing peptides. Amino acid isomerization changes the peptide’s three-dimensional shape, which can significantly affect the molecule’s biological function. The results from this project will provide critical information about how amino acid isomerization impacts cellular communication, which will improve our understanding of how living systems function. In addition to the advancements in basic science, this project will provide training to young scientists in interdisciplinary research to prepare these individuals for a wide range of careers, including those in industry, academics, or government. Some post-translational modifications (e.g., phosphorylation) are well-studied and are understood to play critical roles in regulating protein function. This project focuses on enzyme-catalyzed amino acid isomerization, for which very little information is currently known. Specifically, this project will investigate how endogenous post-translational amino acid isomerization of cell-cell signaling peptides alters interactions with their cell surface receptor proteins. This will be accomplished through three research objectives. The first objective is to thoroughly characterize the role of amino acid isomerization for a known peptide-receptor interaction in Aplysia, an important model organism for understanding the molecular basis of learning, memory, and behavior. The second objective is to investigate amino acid isomerization in Platynereis, a model organism for understanding development and regeneration. The third objective is to build a library of predicted Aplysia neuropeptide G protein-coupled receptors and utilize this library to identify the receptors for known D-amino acid-containing neuropeptides. This project will provide new knowledge about how living systems alter their cellular communication via amino acid isomerization, a severely understudied chemical transformation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

Agricultural Internet-of-Things (Ag-IoT) technologies integrate advanced wireless communication capabilities into intelligent farming devices to boost productivity, profitability, and environmental sustainability. However, the rapid deployment and complex nature of Ag-IoT have left many security and privacy risks un-addressed. As a result, the vulnerabilities of Ag-IoT networks could be potentially exploited. To secure the diverse and complex technologies deployed on farms, proposed solutions need to scale and be highly interoperable. This project develops new techniques that enable scalable and interoperable secure operations for wireless enabled devices in a modern farm setting. The project includes three research efforts (1) scalable trust establishment for chirp spread spectrum (CSS) modulation-based wireless nodes, (2) soil-adaptive trust establishment for underground IoT nodes, and (3) soil-assisted scalable trust establishment for over-the-air IoT nodes. The research outcomes of this project will be disseminated through publications and new course modules. The project promotes cybersecurity and wireless technology in workforce development and broadens the participation of students from underrepresented groups in computing. The team proposes a solid plan for K-12 outreach activities such as cybersecurity day for high school students. This project is jointly funded by the NSF SaTC program, and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

Optical fiber networks, forming the backbone of modern internet and telecommunication systems, are undergoing rapid transformations to accommodate burgeoning data demands and emerging business requirements. The complexity and cost of developing and evaluating new algorithms and protocols on physical platforms necessitate an alternative approach, making network simulation tools indispensable. These tools offer a cost-effective, flexible solution for network design and planning. The accuracy of network simulations is paramount in predicting the real-world behavior of optical networks. Precise modeling ensures that the simulated network’s performance mirrors actual operations, aiding in identifying potential issues, optimizing network performance, and ensuring efficient resource utilization. Incorporating physical layer characteristics in simulations is vital to account for signal degradation, noise, and interference, significantly impacting network performance metrics like throughput, latency, and reliability. With an international collaboration partner at the Indian Institute of Technology - Madras (IITM), the project team at the University of Nebraska-Lincoln (UNL) will contribute to a greater understanding of multi-core coherent optical communication networks, informed by lab and field measurements, resulting in the development of high-fidelity physical layer models and efficient network layer algorithms. The goal of this project is to enhance our understanding of physical models of optical elements and fiber systems, which would then be used to improve optical networking technologies. The project sets out to achieve this by (1) implementing the Optical Phase Conjugators in a field testbed scenario, demonstrating its practical feasibility, and incorporating the physical layer model into network simulation; (2) physical layer implementation of space division multiplexing in four core fibers in a laboratory environment and incorporating the corresponding physical layer models in the network layer; and (3) developing efficient resource allocation algorithms for utilizing the cores in multi-core networks. This includes exploring both direct and coherent detection mechanisms, optical phase conjugation, and space division multiplexing and the incorporation of our novel high-fidelity physical layer models. This project will facilitate a path for integrating physical layer modeling with network layer activities in optical networks. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

Software verification is an essential and widely used approach to ensure software works as expected. Software quality teams use verification tools that automatically search for software bugs. However, there are many such tools available to verify software. To compare these tools, the verification community organizes the SV-COMP software verification competition event. It runs verifiers on sample programs called benchmarks. Benchmarks can become outdated, thus no longer representing modern software. This can lead to verifiers falsely reporting that software is bug-free. To avoid this problem, SV-COMP needs to update its benchmark programs with new programs from online repositories with lots of existing code. However, converting these programs into usable benchmarks is a slow and difficult task. The Adaptable Realistic Benchmark Generator for Verification (ARG-V) project aims to make this process faster and easier. The project’s novelties are: (1) automatically finding and converting code repository programs into SV-COMP benchmarks, and (2) classifying the new benchmarks. The project's impacts are: (1) strengthening verification tools’ ability to find bugs, and (2) involving the verification community in the creation and classification of benchmark programs. The project contributes to the education of undergraduate and graduate students by developing benchmarking course modules and providing professional training. The goal of the ARG-V infrastructure is to automatically obtain a current, realistic set of benchmarks for program verifiers in the SV-COMP format. Because verifiers interpret program semantics in depth, they design different reasoning engines for specific program constructs, e.g., integer operations vs. floating-point operations. This project leverages existing infrastructure to automatically locate candidate benchmark programs from open-source repositories that contain these program constructs. The ARG-V infrastructure then applies systematic, user-defined transformations to the candidate programs to prepare them for use as benchmarks in SV-COMP. This project advances the state of the art by providing an automated solution for benchmark generation that creates realistic benchmarks from real-world programs. In addition, the project investigates the classification of the obtained benchmarks based on the specific program features and type of analysis used in verification. The built infrastructure is made available to the program verification community for use in their research, resulting in improved benchmarking and evaluation of future program verifiers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

This project concerns one of humanity’s greatest challenges – how to slow down, halt, or mitigate the continued loss of biodiversity on Earth. The world is losing much of its animal biodiversity, and populations of large-bodied mammals are declining at an alarming rate. Their decline has serious consequences because large mammals have important roles within ecosystems, which are not replicated by smaller-bodied animals. Not surprisingly, a major focus of conservation, biology, and wildlife management efforts today are geared towards developing an understanding of how this biodiversity loss may impact contemporary ecosystems, and what we can do about it. The consequences of biodiversity loss on ecosystem function can take decades or even centuries to manifest, and so this is where a paleontological, or longer time, perspective can help. The migration of humans into the Americas at the terminal Pleistocene (~13,000 years ago) led to the extinction of >150 species of the largest mammals on the continents, including mammoths, llamas, horses, camels, giant ground sloths, the cave lion, and saber-toothed cats. Examining the role of these extinct mammals, and what happened to the surviving mammals after their extinction, can help us understand what might happen following biodiversity extinction in the future. Thus, this project provides critical baseline information for conservation efforts, as well as insights into the functioning of modern mammal communities. Broader impacts of this work include educational and public outreach, student training, and contributions to scientific infrastructure from the identification and accessioning of fossil materials. The research team will quantify the ecological legacy of the terminal Pleistocene megafaunal extinction on mammal communities in the Edward’s Plateau region of Texas. Building on an unparalleled late Quaternary fossil record of extinct and surviving mammals compiled by the researchers, diet (through stable isotope analysis of preserved collagen in bones), morphology (through 2D and 3D imaging), and ecological interactions (through modeling and simulations) will be characterized at eight key time intervals spanning the past 20,000 years. The overall aim is to characterize the consequences of species extinction on communities, on earth systems, and on surviving animals. Further, the research team will quantify if and how communities recovered, and investigate whether these patterns were influenced by changing climates or by the acceleration and expansion of human impacts over the late Holocene. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

The Sandhills Region of Nebraska is one of the largest intact temperate grasslands in the world. The landscape of the Sandhills consists of grass-covered sand dunes overlaying the Ogallala Aquifer, a vast underground reservoir that supports diverse communities of plants and animals. The most diverse and abundant animals in the Sandhills are the little known and seldom observed microscopic nematodes. Nematodes have adapted to a wide range of Sandhills habitats, from pristine groundwater-fed streams to alkaline lakes with a water chemistry that restricts most other forms of life. It is unknown what allows nematodes to survive in these extreme environments. However, given the combined effects of climate change and groundwater depletion, the Nebraska Sandhills provide a natural experiment to study the forces that drive diversity and adaptations in this ubiquitous group of organisms. This research will provide insights into how nematodes respond to environmental shifts resulting from the changing climate. Graduate and undergraduate students will engage with a multidisciplinary team of researchers to address these topical questions. Of specific interest to this research are freshwater nematodes in three families (i.e., Tobrilidae, Plectidae, and Monhysteridae) representing three evolutionarily distinct lineages known for their physiological and morphological plasticity but also critical to understanding nematode evolution and phylogeny. There are three main research objectives: 1) describing new species from three targeted nematode families, 2) determining their spatial distributions across the Sandhills, and 3) establishing their taxonomic and ecological context. To accomplish these objectives, three Sandhills regions will be sampled including Alkaline Lakes in Year 1, Sheridan and Cherry Counties in Year 2, and the eastern Sandhills in Year 3 for a total of 128 samples. Samples will be collected from a wide range of aquatic habitats such as lakes, fens/wet meadows, and streams/rivers. Each sample will be split into four aliquots and subsequently used for archiving, individual nematode specimen morphological and barcoding analyses, community metabarcoding and mitochondrial metagenomics, and biochemistry. These data will then be analyzed phylogenetically, and other analyses will include species delimitation, phylogenetic endemism, and multiple regression models and co-occurrence networks. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

The GeoNet project aims to tackle the numerous challenges faced by secondary teachers in teaching Earth System Sciences, important science disciplines for society in our changing world. In Nebraska, approximately 76% of school districts have opted to incorporate Geoscience topics into existing physical science and/or biology courses rather than offering a dedicated Earth and Space Science (ESS) course. This trend underscores a challenge: the dearth of resources available to effectively integrate Earth System Science into other science disciplines, leaving teachers to grapple with this issue independently. Unfortunately, this challenge is often exacerbated by teachers' limited knowledge of Earth System Science content. Furthermore, there is a notable gap in teachers' awareness of Geoscience career pathways. Given that educators play a pivotal role in shaping students' career aspirations, this knowledge deficit has the potential to impede the influx of students into the Geosciences. The GeoNet project endeavors to address these multifaceted challenges through an intensive professional development program tailored to secondary teachers. The goals of 'GeoNet' are as follows: (1) Establish a robust network of engaged secondary teachers across various science disciplines. (2) Provide guidance to teachers in crafting new curricula infused with integrated geoscience themes and Nebraska-specific geoscience phenomena. (3) Facilitate the ongoing incorporation of geoscience content within a NGSS framework across diverse science subjects. (4) Enhance the foundational knowledge and teaching efficacy of educators in the realm of geosciences. (5) Heighten teacher awareness and perception of geoscience career opportunities and pathways. To realize these goals, the team proposes the establishment of a geoscience learning community and network (GeoNet) comprised of a set of master teacher leaders who will collaborate closely with the principal investigators to nurture additional cohorts of secondary science educators. Through sustained professional development, exposure to field-based geological phenomena, integration with local experts and resources, and community-building events, teachers’ enhanced knowledge and exposure to geosciences will aid their collaborative professional development and implementation of innovative curricula integrating geoscience themes. Through the implementation of this project, we anticipate significant improvements in geoscience education, thereby enriching students' comprehension of Earth systems and fostering interest in geoscience careers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-06

In less than 20 years, the prevalence of obesity increased from 30.5% to 42.4%, and the prevalence of severe obesity increased from 4.7% to 9.2%. The mission of the Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules (NPOD) is to prevent, treat and cure obesity and co-morbidities with bioactive food compounds. The focus on bioactive food compounds is a unique niche in obesity research and has afforded NPOD with tools to ameliorate obesity and co-morbidities through consumer-friendly, economically feasible adjustments to their diets with a negligible effect on taste. In Phases 1 and 2, NPOD has increased its member base 4.9-fold to 59 faculty in 26 departments (representing 571 trainees) at University of Nebraska- Lincoln (UNL), University of Nebraska Medical Center (UNMC), and University of Nebraska Omaha. This growth was achieved through 9 tenure-leading faculty appointments, recruiting faculty not previously engaged in obesity research, and providing a home for obesity researchers who previously worked in isolation. NPOD members have secured nearly $200 million in external research funding, a nearly 36:1 return on institutional investment. UNL and UNMC have contributed nearly 3500 sq. ft. and $5.5 million to NPOD in Phases 1 and 2 with additional institutional commitments in Phase 3 and the 3 years following. Most of the new space was leveraged to develop a new Research Core (Biomedical and Obesity Research Core, BORC). BORC has fulfilled 1400 service requests per year that generated $266,335 in annual revenue. NPOD is poised to continue its strong trajectory toward sustainability in Phase 3 and beyond through 5 pillars of NPOD sustainability: institutional commitments, F&A costs, philanthropy, program project grants, and NIDDK funding through the Nutrition and Obesity Research Center (NORC) mechanism. Specific Aim 1: Implement NPOD's succession plan to achieve sustainability through preparing former Research Project Leaders and a new hire to serve as future Center Director. Specific Aim 2: Lead BORC into long-term sustainability by attracting new users, particularly external users, through continued alignment of services offered with user needs and strengthened promotional activities. Specific Aim 3: Increase NPOD's critical mass of investigators conducting clinically important research through the Center's Pilot Grants Program and a new faculty hire in a tenure leading appointment and expertise in electronic health records. Specific Aim 4: Increase NPOD's revenue by prioritizing pilot grant applications with a high likelihood of leading to large-scale federal funding. Specific Aim 5: Intensify efforts to convert NPOD to an NIDDK-funded NORC through nurturing a group of obesity and nutrition researchers.

NSF Awards · FY 2024 · 2024-06

This project is focused on structural and classification problems of amenable operator algebras. The theory of operator algebras began in the 1930s with the goal of creating a mathematically rigorous foundation for Heisenberg's approach to quantum mechanics. In Heisenberg's work, observable physical quantities are represented by certain linear operators on Hilbert space (roughly, infinite matrices of complex numbers). One of the most famous results of quantum mechanics is Heisenberg's uncertainty principle that the momentum and position of a particle cannot be known simultaneously. The mathematically rigorous version of this statement is that the operators P and Q which measure position and momentum do not commute, i.e., PQ and QP are not equal (there is, however, a precise formula relating P and Q). Operator algebras is the study of algebraic relations between collections of operators. Amenable C*-algebras form a particularly important class of operator algebras. A large-scale effort over the last several decades has shown that, under relatively mild (though still somewhat mysterious) additional hypotheses, the simple (i.e., indecomposable) amenable C*-algebras can be completely classified. The main goals of this project are to further examine the extra conditions needed for classification, with a view toward more powerful classification results, and to study of the finer structure of the classifiable operator algebras, including their symmetries. The project will also enhance the mathematics workforce through research opportunities for graduate students, instructional workshops and seminars, and expository material on the main topics of research. Recent progress in Elliott's Program has shown that separable, simple, nuclear, Z-stable C*-algebras in the UCT class are classified up to isomorphism via their operator K-theory groups, their trace simplex, and the pairing between them. The Z-stability condition is known to be necessary and is currently the most difficult hypothesis to verify in practice. The Toms-Winter conjecture predicts that under the other hypothesis, Z-stability follows from an a priori weaker condition known as strict comparison. Part of the goal of the project is to examine this conjecture. It is a long-standing open question if every separable nuclear C*-algebra satisfies the UCT. While the UCT condition is usually easily verified in concrete examples (through a series of deep results in operator K-theory), the UCT continues to be a significant theoretical barrier. This project will examine the possibility of obtaining classification results without a UCT assumption, at the expense of augmenting the Elliott invariant with KK-theoretic data. Such classification results without the UCT will be crucial in advancing the structure and classification theory of non-simple nuclear C*-algebras and of group actions on (simple) nuclear C*-algebras. Indeed, all prior works in this direction suggests that variants of KK-theory accounting for the ideal structure and/or the group action on the C*-algebra will be necessary, and even in most concrete examples, there are no satisfactory analogues of the UCT which account for this extra structure on KK-theory. It will thus be necessary to work with KK-theory more directly than has been done previously in the (stably finite) classification theory. Progress in this direction will set the stage for the next stages in the structure and classification theory of nuclear C*-algebras and group actions on such C*-algebras. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-06

PROJECT SUMMARY/ABSTRACT Nicotine is the primary addictive agent driving chronic smoking/vaping. Women experience greater nicotine use vulnerability, insofar that they become addicted to nicotine faster than men and exhibit higher smoking relapse rates. Women are also at greater risk of smoking-related heart attacks, cancers, and mortality. Hormonal contraceptives typically contain a synthetic estrogen (e.g., ethinyl estradiol or EE) and/or a progestin (e.g., levonorgestrel or LEVO), and are taken by 50% of premenopausal smokers. Contraceptive hormones are associated with higher smoking rates, enhanced nicotine reward, and a greater risk of smoking-related illness and mortality. Hormonal contraceptives are thus clearly linked with the public health burden of smoking. A better understanding of factors driving enhanced nicotine use vulnerability amongst women, and how hormonal contraceptives work to augment that vulnerability, would be of enormous benefit. The reinforcing effects of nicotine are weak compared to the tenacious addiction that nicotine maintains, leading the field to seek other factors involved in the development of nicotine use disorder. Indeed, environmental stimuli that commonly co- occur with nicotine (e.g., smell, taste, or sight of cigarettes/vapes) have been found to play a large role in smoking/vaping maintenance, particularly for women smokers. The enhanced import of environmental factors in nicotine intake extends to female rats, suggesting this sex-linked disparity may be rooted in biology more generally, or perhaps sex hormones more specifically. One such environmental factor is the enhancement by nicotine of the reinforcing value of other rewarding stimuli. In rats, the species studied here, our lab and others have found that responding for nicotine infusions alone was not reliably above saline suggesting a lack of primary reinforcement by nicotine. However, when nicotine infusions co-occurred with weakly reinforcing visual stimuli (e.g., a brief light presentation), nicotine-maintained responding increased up to eight-fold. This synergistic effect of nicotine reward-enhancement on nicotine intake was more prominent in female rats. Using a preclinical model of the role of reward-enhancement in nicotine intake, the proposed studies will test whether contraceptive hormones alter nicotine intake via the direct primary reinforcing effects of nicotine, or rather via augmenting the role of reward-enhancement in nicotine self-administration. The Specific Aims will examine the separate effects of EE (Aim 1) and LEVO (Aim 2) on the role of reinforcement and reward-enhancement in an intravenous nicotine self-administration task. To this end, separate groups of ovary-intact female rats will respond for nicotine or saline infusions and will receive daily EE (Aim 1) or LEVO (Aim 2) injections before self- administration sessions. Each rat will undergo separate conditions with access to infusions alone or infusions delivered with a moderately reinforcing visual stimulus. We hypothesize that EE will increase and LEVO will decrease nicotine self-administration and do so via modulating the role of reward-enhancement in nicotine self- administration.

NIH Research Projects · FY 2026 · 2024-05

ABSTRACT Enzyme catalysis is one of the most important phenomena in biochemistry and yet is incompletely understood. New time-resolved serial crystallography methods now allow enzyme catalysis to be observed in real time, in near-physiological conditions, and at atomic resolution, allowing new classes of experiments to be performed. The central goal of this proposal is to both develop and use innovative structural biology methods to understand the underlying physical principles of enzyme function. We will use time-resolved serial crystallography to determine how catalysis changes enzyme structure and dynamics in cysteine-dependent enzymes. Our initial focus is on various enzymes in the DJ-1 superfamily involved in parkinsonian neurodegeneration, isocyanide antibiotic destruction, and carbonyl stress mitigation. A second contributor to enzyme catalysis is quantum mechanical effects, some of which are becoming accessible to large computational simulations and experimental characterization. We will determine how neglected quantum mechanical effects affect enzyme catalysis by incorporating time-resolved crystallography, computation, and biochemistry to investigate pervasive evidence of quantum mechanical charge transfer in catalysis. These scientific goals will be pursued concurrently with the development of new methods to expand the scope and power of time-resolved structural biology experiments by reducing barriers to performing these experiments. In total, this work will use new technologies to improve the understanding of fundamental enzymatic phenomena and broaden the application of time-resolved structural biology.

NIH Research Projects · FY 2025 · 2024-04

SUMMARY Gene delivery via the oral route offers a promising strategy for improving gene-based therapy outcomes. The non-invasive nature of oral delivery allows for ease of dosing, which can promote convenience and a high rate of patient compliance. Moreover, oral administration facilitates both local and systemic production of therapeutic genes. For local gene therapy for gastrointestinal (GI) diseases (e.g., metabolic and nutritional defects, inflammatory bowel diseases and colon cancers), the oral route allows direct access to the affected tissue. However, the highly vascularized nature of the GI tract also makes oral gene delivery a viable option for administering systemic therapies, where transfection within intestinal cells results in production of protein that is delivered into the bloodstream and circulated systemically. In addition, oral DNA delivery can be used as a vaccination strategy, providing for both systemic and mucosal immunity. Although there is potential for oral gene delivery to treat and vaccinate against a wide variety of diseases, the efficacy of nonviral delivery methods is limited by carrier materials that cannot prevent DNA payload degradation in the harsh conditions of the GI tract nor promote uptake by intestinal cells, which results in low transgene expression. To overcome challenges associated with oral gene delivery, we propose to develop a novel, biological-based delivery platform by loading outer membrane vesicles (OMVs) derived from commensal gut bacteria with plasmid DNA to create DNA-loaded OMV nanocarriers (DNA-OMV NCs). OMVs are produced via budding of bacterial outer membranes and function as a natural communication system for bacteria. OMVs protect and deliver secreted material, allowing bacteria to influence their environment. Numerous commensal (non-pathogenic) bacteria residing in the human GI tract secrete OMVs, and preliminary results from our team show that OMVs from commensal Escherichia coli (E. coli) isolated from the human GI tract can be internalized by both intestinal epithelial cells and macrophages, elicit a range of pro- or anti-inflammatory cytokine responses from macrophages, and survive gastric transit when orally administered to mice. Moreover, we have shown in preliminary work that we can load OMVs (from a lab strain of E. coli) with pDNA to create DNA-OMV NCs. We hypothesize that a DNA-OMV NC delivery platform will protect loaded DNA through GI transit, facilitate uptake by epithelial cells and macrophages, elicit tunable cytokine responses, and enable effective in vivo transfection. We will pursue two aims: 1) Screen OMVs isolated from gut commensal E. coli strains for internalization, cytotoxicity, and immune modulation to develop a library of OMVs for use as NCs for oral gene delivery; 2) Develop methods to produce DNA-OMV NCs and evaluate their abilities to protect DNA cargo, modulate immune profiles, and mediate transfection. Specific to the Awards Supporting Cutting-Edge Technologies for Translational Science (ASCETTS) funding opportunity, we expect to develop a tunable, bio-inspired platform for oral gene delivery that leverages natural host-bacterial interactions and is suitable for broad utilization in therapeutic applications, ranging from gene therapy to vaccination.

NIH Research Projects · FY 2025 · 2024-01

Project Summary: The eukaryotic cytoskeleton is a highly dynamic, yet, at the same time, highly organized network of protein filaments, the most important being actin and microtubules (MTs). MTs are essential for defining cellular shape and structure, as well as trafficking membrane-bound vesicles, organelles, and, during cell division, chromosomes. To perform these functions, the cell must tightly regulate the formation of new MTs via the process of MT nucleation. Cells primarily regulate MT nucleation by controlling the universal MT nucleator, the γ-tubulin ring complex (γ-TuRC). To initiate MT nucleation, γ-TuRC is recruited to specialized regions known as MT organizing centers (MTOCs), where γ-TuRC is activated and spatially oriented so that the resulting MT has the appropriate polarity. Many of the first discovered MTOCs are also the most complex, including the basal body, which generates flagellar MTs, and the centrosome, which generates many spindle MTs. These classical MTOCs are composed of up to hundreds of unique proteins organized into complicated large-scale structures. This makes them poorly suited to uncover MTOC function: namely, how MTOCs recruit, orient, and activate γ-TuRC. To will illuminate these three basic principles by investigating γ-TuRC regulation in two model essential, yet simple MTOCs: in the K99 phase, the vertebrate MT branch site and, in the R00 phase, the nuclear plaque of model excavate Trypanosoma brucei. I will use a combination of reconstitution experiments and cryo-electron tomography to uncover how these divergent, model MTOCs use shared principles to regulate γ-TuRC. My results will both help the research community understand MTOC function, as well as provide new therapeutic avenues to treat infection by parasitic excavates, an emerging global health threat. As proposed, this research plan will allow me to successfully pivot from my postdoctoral work with Dr. Petry, an expert on vertebrate MT nucleation, to establish my own, independent research focus on excavate MT nucleation and launch as an independent investigator. In addition, I have established a mentor team for the K99 phase of the proposal to train me in key technical areas that I require for the independent R00 phase. First, I will master a TIRF-based assay pioneered in Dr. Petry’s lab that allows visualization of microtubule nucleation at the single molecule level. Second, which I will learn cryo-electron tomography, a key technique of my proposal, in collaboration with world experts Dr. Andreas Hoenger and Dr. Martin Beck. In learning this technique, I will benefit from my mentorship team of Dr. Petry, Dr. Hoenger, Dr. Beck, and the cutting-edge vibrant structural biology community at Princeton as a whole. Finally, I have recruited Dr. Chris de Graffenried, an expert in excavate biology, to serve as a scientific mentor as I transition into this new model system. Through the training phase of the proposal and beyond, I will learn from my mentor team how to successfully lead a research group that fearlessly leverages a broad range of techniques and disciplines to answer critical scientific questions, and will, in the R00 phase, establish this group at a leading U.S. institution.