Author: orandall

Several methods have been developed to inactivate virus particles. These inactivation methods must be effective and reliable to prevent the accidental spread of viruses. It is crucial to completely inactivate high-risk agents, such as SARS-CoV-2, before they are removed from high-level biocontainment facilities for further handling. However, it is unclear whether common methods of virus inactivation are effective in inactivating positive-sense RNA viruses. Positive-sense RNA viruses contain RNA genomes of positive polarity and include viruses which can cause serious illness in humans and often result in epidemics and pandemics. The genome of a positive-sense RNA directly serves as messenger RNA (mRNA), thus, can be immediately translated by host cells to produce infectious virions. Therefore, if viral RNA is not properly inactivated during inactivation procedures, the intact RNA can potentially cause infection if introduced into permissive cells. This underscores the need for inactivation protocols that ensure complete inactivation of viral RNA to prevent the accidental release of virus particles into the environment.

Validation for the absence of RNA infectivity after virus inactivation is rarely performed, raising significant biosecurity risks associated with positive-sense RNA viruses. Despite the widespread use of inactivating agents in research labs, there are no standardized protocols for validating RNA infectivity. Testing methods for RNA infectivity are cumbersome and require expertise in RNA, cell culture, and transfection techniques. This study will systematically evaluate the efficacy of existing viral RNA inactivation methods, focusing on their ability to render viral RNA non-infectious. We will develop reagents and protocols required for infectivity testing of viral RNA. By employing appropriate controls and rigorous validation techniques, we will establish standardized protocols for the inactivation of positive-sense viruses and their RNA.

Funder: Centers for Disease Control and Prevention 

Amount: $846,421 

PI: Lok Joshi, College of Veterinary Medicine 

New theoretical and experimental methods in chemical physics being developed by the PIs provide great opportunities for the study of molecular species and chemical reactions of fundamental importance in combustion processes. In this research, high level quantum mechanical formalisms are a significant source of critical predictions concerning molecular systems that may be challenging for experiments. Moreover, our helium droplet experiments have opened whole new vistas for the spectroscopic study of molecular species relevant to combustion environments. Theoretical developments proposed herein include a focus on obtaining highly accurate energetics for species pertinent to elementary reactions. Experimental developments include strategies to characterize transient combustion intermediates associated with low temperature hydrocarbon oxidation processes, which have been difficult to probe with other methodologies. The combination of theory and experiment to solve problems inaccessible to either alone is a hallmark of this research.

Funder: U.S. Department of Energy 

Amount: $927,610 

PI: Gary Douberly, Franklin College of Arts and Sciences, Department of Chemistry

The broader impact of this Partnerships for Innovation – Research Partnerships (PFI-RP) project is to enhance the reliability and security of electrical devices and networks within modern infrastructure including, but not limited to, buildings, manufacturing systems, and hospitals. This PFI-RP project introduces a smart sensor capable of detecting anomalies, pinpointing their locations, and diagnosing issues in electrical devices and networks. The algorithms and designs developed may also contribute to the broader field of anomaly detection and diagnosis beyond electrical signals. The project team will provide training to undergraduate and graduate students, in addition to middle school teachers. Collaborations with the Peach State Louis Stokes Alliances for Minority Participation (LSAMP) and the NSF Research Experiences for Undergraduates (REU) programs will be nurtured to support these efforts. Strategic partnerships with industry leaders offer vital insights and provide educational and leadership opportunities for graduate students and postdoctoral researchers. The project brings together a strong partnership between academia and prominent industry leaders, including General Electric (GE), United States Robins Air Force Base (RAFB), Siemens America (Siemens), and NEC Laboratories America (NEC) to explore the commercialization of an electrical sensing technology for scalable anomaly detection and diagnosis in electrical devices and networks. The impact spans from small-scale applications (e.g., homes, buildings, factories) to large-scale scenarios (e.g., distribution networks to transmission networks of main grids). This adaptability facilitates dynamic data processing, allowing the installation of varying numbers of smart sensors. Additionally, the technology offers customized programming and low-cost, flexible deployments, which can be easily installed by plugging into an electrical outlet in residential and commercial settings.

Funder: National Science Foundation 

Amount: $1,000,000 

PI: Jin Ye, College of Engineering 

Proteoglycans harboring heparan sulfate (HS) chains are widely found on cell surfaces and in extracellular matrices where they interact with growth factors, receptors, morphogens, and extracellular matrix components and play critical roles in processes such as cell survival, division, migration, differentiation, pathogen binding, and cancer development. HS biosynthesis is a complex process involving initial formation of a linker glycan on proteoglycan core proteins, priming and extension of the HS chains’ polymer backbone, facilitated by the EXT1-EXT2 heterodimeric co-polymerase complex. Homozygous defects in either of these proteins cause embryonic lethality, and heterozygous loss of function has clinical ramifications, including benign tumors. We recently solved the structure of the human EXT1- 2 heterodimeric co-polymerase in complex, providing insights into HS chain synthesis. EXT1 and EXT2 form an obligate heterocomplex of the two homologous proteins. Each protein contains two separate predicted catalytic domains, yet only one of the two domains is active in each protein suggesting that the monomers share catalytic functions. We also discovered an interaction between EXT1-2 and the HS priming enzyme EXTL3. These studies raise important new questions about HS synthesis in vivo and the nature and pathology of HME mutations. This research will advance our understanding of HS biology and its roles in health and disease. Unraveling the mechanisms governing HS backbone synthesis will shed light on the molecular basis of HS-mediated cellular processes and pave the way for future development of targeted interventions.

Funder: National Institutes of Health 

Amount: $1,331,828 

PI: Kelley Moremen, Franklin College of Arts and Sciences, Department of Biochemistry and Molecular Biology 

The project will advance scientific understanding of the effect of multiple stressors on aquatic species of interest to the Department of Defense (DoD) and promote the resilience of the spotted turtle (Clemmys guttata) under anthropogenic and climate-induced stressors on DoD installations. The relative vulnerability of coastal and inland spotted turtle populations to hydrologic alterations, connectivity, and susceptibility will be evaluated using an interdisciplinary approach composed of laboratory, field, and model work. The spotted turtle is currently under review for federal listing. All populations are vulnerable under climate scenarios that reduce wetland hydroperiod. Coastal populations are additionally vulnerable to wetland loss and saltwater intrusion from sea level rise and overwash during major storm events. Thus, hydrology is considered the major climate-induced stressor. Landscape stressors include distance to other suitable wetlands, road density, woody encroachment, and accessibility to potential poaching – a major threat to the species. Field work will focus on turtle movement, population surveys, quantifying stressors at occupied sites, collecting blood samples for measurement of chemical stressors and characterizing turtle health. Lab work will test the effects of salinity and temperature on physiological and immune responses in turtles. The omics-based assays will be conducted on a subset of biological samples collected from the field survey and controlled lab experiments. Our proposal will improve fundamental understanding of how multiple stressors interact to affect the resilience of spotted turtle populations. In addition to providing baseline population data for monitoring future trends, our work would quantify stressors and identify which stressors spotted turtles are most sensitive to, helping prioritize management actions and best management practices (BMPs) for the species.

Funder: U.S. Department of Defense 

Amount: $2,208,377 

PI: Tracey Tuberville, Warnell School of Forestry and Natural Resources

As the U.S. invests in efforts to build its capacity to lead the world in the development of artificial intelligence and other areas of computer science, it faces a critical workforce bottleneck, a shortage of computer scientists to meet workforce demands in industry and academia, coupled with a lack of gender and racial diversity. One way to effectively expand and diversify the computer science workforce is to develop a pathway from community colleges to undergraduate and graduate degree programs. Community college transfer students in computer science are a particularly high-achieving and diverse group, and community colleges are a primary entry point into higher education for many Students of Color, women, first-generation college students, and others who hold a combination of these and other historically minoritized identities in higher education. Despite the talents and assets that transfer students bring to the computer science major, they also face unnecessary barriers at their universities, which constrain their opportunities to become leaders in their field. The goal of this project is to produce new knowledge that will address these barriers and guide efforts to transform university structures, policies, and practices to foster success among community college transfer students in computer science. This study will engage a convergent, multi-phase mixed methods design. Drawing on five years of longitudinal survey and interview data from computer science transfer students and other key university agents (e.g., university faculty, staff, administrators) across six campuses in the California State University system, the project aims to address the following overarching research questions: (1) What are the structures, policies, and practices that community college transfer students identify in shaping their degree trajectories in computer science? (2) From the perspective of key university agents (e.g., advising staff, faculty, administrators), what are the relevant structures, policies, and practices that shape community college transfer student degree trajectories and opportunities in computer science? The inquiry will be informed by social cognitive career theory (SCCT) and theories of administrative burden and street-level bureaucracy. The quantitative stream of this work will rely on descriptive and multivariate analysis of student surveys and registrar data. The qualitative stream of this research will use phenomenological methods, relying on student and university agent interview data to better understand the experienced phenomena (i.e., structures, policies, and practices that shape transfer student trajectories in computer science). This approach aligns with the research questions, which collectively focus on how participants with varying positionalities (e.g., student, staff, faculty) make meaning of the structures, policies, and practices that shape community college transfer student success and degree trajectories.

Funder: National Science Foundation 

Amount: $1,496,458 

PI: Jennifer Blaney, Louise McBee Institute of Higher Education 

Project Summary Chromosome breakage can generate extraordinary genetic novelty that is selected upon during tumor progression. One commonly observed feature of cancer is the breakage-fusion-bridge (BFB) cycle, where double-strand breaks set off a chain reaction that leads to copy number variations and complex chromosome shattering events. The BFB cycle was first described in maize by Barbara McClintock in the 1940s and led to the discovery of transposable elements (TEs). Two types of TEs, Activator/Dissociation (Ac/Ds) and Suppressor-mutator (En/Spm), burst from her BFB samples, leading her to hypothesize that chromosome breakage can lead to a genome-wide response she called “genome shock.” Her observation that BFB activates previously dormant transposable elements suggests that major epigenetic changes accompany BFB, likely compromising DNA methylation and heterochromatin. DNA demethylation and TE activation are also observed in many cancers, but causal relationships between BFB and demethylation have not been clearly established. Unlike in animals, maize tolerates the transmission of major chromosomal abnormalities through gametogenesis, greatly facilitating downstream studies. We have developed a system for inducing the BFB cycle in maize and demonstrated its ability to induce genetic instability and large chromosomal abnormalities. In our approach, an array of LexO repeats inserted on a chromosome arm is combined with a LexA- CENH3 transgene and initiates a second centromere. With long read sequencing and ChIP-seq assays, we will analyze the genomic and epigenomic changes that follow BFB over multiple generations. We will also deploy high-sensitivity screens for TE activation. These approaches will allow us to test at the molecular level the extent to which genome reordering by BFB leads to genetic and epigenetic changes in otherwise wild type genetic backgrounds. The proposed research will establish a new model for investigating BFB in complex eukaryotes and provide greater insight into how the BFB cycle impacts epigenetic processes that have the potential to further destabilize the genome. In addition, the work will provide a direct test of the genome shock hypothesis, which has provided an important guidepost for interpreting the chromosome rearrangements in cancer as well as hundreds of other genome restructuring events in animals, plants, and fungi.

Funder: National Institutes of Health 

Amount: $1,849,815 

PI: R. Kelly Dawe, Franklin College of Arts and Sciences, Department of Plant Biology 

Abstract Infection with the protozoan parasite Trypanosoma cruzi is generally controlled but often not eliminated by host immune responses. In humans and many other hosts, this persistent infection ultimately results in muscle tissue damage known as Chagas disease. It is widely accepted that the early detection and rapid treatment of T. cruzi improves treatment outcomes and reduces the chances of heart damage and that parasitological cure could provide lasting immunity to reinfection and disease. However, there are limited data that specifically support these ideas. In addition to humans, T. cruzi also impacts many other mammalian species, among these dogs, that develop very similar patterns of immune control, disease development, and response to therapy, as humans. The project proposed herein takes advantage of a natural setting of high intensity infection in working dogs in south Texas to address questions of critical importance to the management of infection and disease in humans exposed to infection by T. cruzi. The question of the relative benefit of treatment soon after infection will be explored by comparing treatment outcomes using a new, high rate-of-cure treatment regimen, delivered to dogs either within months of infection, or delayed by several years. Treatment success will be evaluated using parasitological (deeply sampled blood qPCR and hemoculture), immunological (declining antibody titers) and clinical disease (blood cardiac troponin concentration, EKG and echocardiographic changes). In dogs in which parasitological cure is achieved by drug therapy, we will determine the long-term benefits of prior infection exposure by assessing reinfection rates and resistance to cardiac disease for dogs in this setting of high transmission risk. The immunological correlates of increased resistance to infection and disease will be determined by comparing the potency of anti-T. cruzi humoral and cellular immune responses to reinfection potential and ultimate pattern of disease. Lastly, the benefit of a reduced parasite burden, rather than parasitological cure, to disease development will be investigated in this same setting. Overall, this project takes advantage of one of the major benefits of work in Chagas disease, that of the highly similar course of infection and disease in naturally infected non-human mammals, to investigate questions of prime importance to the management of human Chagas disease. The work takes advantage of the cumulative and broad skill set of scientists and clinicians with a long history of work in human and animal Chagas disease and established record of collaboration in this highly accessible, high infection-risk setting. Completion of these studies will provide information that for ethical and infection dynamic reasons is likely unattainable in humans but that is highly relevant to designing strategies for management of T. cruzi infection in humans, including assessment of the need for very early detection and treatment, the requirement or not for parasitologic cure for the prevention of clinical disease, and the likelihood of reinfections and subsequent clinical disease in subjects who have received curative treatments.

Funder: National Institutes of Health 

Amount: $2,548,943 

PI: Rick Tarleton, Franklin College of Arts and Sciences, Department of Cellular Biology 

The development of a competent science, technology, engineering, mathematics, and computing (STEM+C) workforce in the era of generative artificial intelligence (GenAI) is crucial for the nation’s economic growth, security, and global competitiveness. To achieve this goal, initiatives that combine a robust understanding of core STEM concepts with competence in computational thinking (CT) and AI are needed. With this goal in mind, the National Center on Generative AI for Uplifting STEM+C Education (GENIUS Center) will integrate generative AI with the teaching and learning of science and engineering practices through a GenAI learning agent named GenAgent, that will serve as a mentor, learning buddy, collaborative learning agent, and teacher assistant to promote six key middle school science and engineering practices (SEPs).

The GENIUS Center will (1) conduct exploratory studies to examine how generative AI is currently used in classrooms to improve teaching and learning outcomes, (2) informed by the exploratory studies, the Center will develop, test, and refine the GenAgent system in science classrooms, and (3) conduct a pilot study to assess the promise of GenAgent for improving learners’ education outcomes. In addition, the GENIUS Center will provide national leadership and outreach activities on the responsible use of GenAI to improve learner outcomes.

Funder: U.S. Department of Education 

Amount: $10,000,000 

PI: Xiaoming Zhai, Mary Frances Early College of Education 

The BioFoundry: Glycoscience Resources, Education, And Training (BioF:GREAT) will develop new research, technologies, and instructional experiences to allow a broader adoption of glycoscience into research environments and education curriculums. Although glycans, also referred to as complex carbohydrates, are one of the four classes of biomolecules found in all living organisms, they have been consistently understudied in the laboratory and undertaught in the classroom. This is despite the fact that biofuel and biomaterial efforts rely heavily on glycan biomass from plants, the vast majority of biologics in medicine are glycoproteins, and glycans are found on cell surfaces of all living cells where they contribute to cell interactions and diverse biological functions. Unlike DNA/RNA and proteins, glycans are rarely linear polymers and are not generated by template-based processes. This complexity has made them difficult to study at the bench and challenging to teach in the classroom. BioF:GREAT will leverage a broad range of expertise, including AI and machine learning, to generate research tools and technologies, while also developing and deploying novel instructional and training strategies, resources, research materials, and automated tools in the field to propel glycoscience into the scientific mainstream and lead to paradigm shifts in glycoscience education. BioF:GREAT discoveries and deliverables are expected to lead to commercial applications in bioenergy, bioengineering, biomaterials, and biomedicine. The BioFoundry: Glycoscience Resources, Education, And Training (BioF:GREAT) will take advantage of the Complex Carbohydrate Research Center (CCRC) at the University of Georgia (UGA), home to one of the largest communities of glycobiologists in the world, coupled with UGA experts in bioinformatics/machine learning and pedagogy/evaluation. The Research team will focus on three synergistic goals: 1) bioinformatic tools/machine learning/artificial intelligence (AI) to predict and define glycoenzymes and glycoproteins, 2) glycoenzyme expression, characterization, and manipulation, and 3) mass spectrometry-facilitated analyses of glycan modifications. The Technology Development team will focus on four themes that will generate 1) expression libraries for glycoenzymes from diverse species sources, 2) fine-tuned protein language models and new user-friendly informatics tools for classifying and predicting glycoenzymes and site-specific glycosylation of glycoproteins, 3) engineered glycoenzymes for generating novel chemical biology tools, and 4) species-agnostic methods for the mass spectrometry-based analyses of glycoproteins. The User Facility will provide hands-on training and service using cutting-edge computational, enzymatic, and analytical glycoscience approaches. Collaboration among User Facility, Research, and Technology Development teams will lead to the deployment of new technologies to catalyze in-house research and technology development efforts. The User Facility will equally focus on external glycobiology research projects spanning the tree of life in partnerships with scientists at R1 and non-R1 schools including minority-, primarily undergraduate-, and EPSCoR-serving institutions. The Education/Instruction team will establish and evaluate a suite of instructional experiences, including small modules for existing chemistry/biology courses, dedicated stand-alone glycoscience courses at the undergraduate/graduate level, and hands-on summer courses for beginners and experts with rigorous attention to best pedagogical practices and evaluation for improvement. Our Platform-Sharing team will facilitate the transfer of deliverables from the bench and the classroom to academic, government, and commercial/industrial research communities using a knowledge graph framework consistent with the Prototype Open Knowledge Network (Proto-OKN). By providing equitable access to advanced infrastructure and resources in glycoscience, BioF:GREAT will advance scientific inquiry and education in biosciences across all kingdoms of life.

Funder: National Science Foundation 

Amount: $18,000,000 

PI: Lance Wells, Franklin College of Arts and Sciences, Department of Biochemistry and Molecular Biology