Category: Notable Grants

Brown spot needle blight (BSNB), caused by Lecanosticta acicola, is a foliar disease affecting several species of pines and is a major concern for many commercial plantations globally. The use of host resistance is a promising avenue to mitigate the damage caused by the disease, however, little has been done to characterize resistance and facilitate selection in the radiata pine (Pinus radiata) system, despite the high susceptibility of the species and its commercial importance in many regions. The scope of this proposal is to investigate and characterize the resistance of radiata pine to BSNB, both through classical quantitative genetics and by uncovering the underlying genetic mechanisms. Specific objectives include (i) optimizing controlled inoculation protocols for infecting radiata pine with L. acicola; (ii) infecting a set of New Zealand radiata pine families to assess their susceptibility to BSNB, and establish heritability values for BSNB resistance in radiata pine; (iii) performing transcriptomic and metabolomic analyses on radiata pine seedlings, to understand host genetic responses, as well as chemical and morphological responses; (iv) identifying genome‐wide molecular markers for the rapid selection of radiata pine resistant to BSNB; and (v) comparing genomic regions potentially associated with resistance to BSNB with those involved in the interaction with other needle diseases, for example Dothistroma Needle Blight and Red Needle Cast.

Funder: Radiata Pine Breeding Company

Amount: $294,994

PI: Caterina Villari, Warnell School of Forestry and Natural Resources

Nematodes are among the top yield-robbers encountered by soybean farmers across the U.S. Almost all soybean cyst nematode (SCN)-resistant varieties in U.S. soybean production are derived from two genetic sources, imposing risk of genetic vulnerability and resistance breakdown. Soybean breeders and growers are limited in genetic sources for nematode resistance with competitive yield, which places U.S. soybean production at risk. Discovery of novel nematode resistance from genetically diverse sources is essential for sustainable soybean production. Deployment of resistant varieties will improve U.S. soybean production and protect yields and farmers’ income. New breeding populations were created combining SCN-resistant Peking and other new resistant sources with traits valuable to commodity soybean production and specialty markets. Seven major loci for resistance to five nematode populations were identified using Genome-Wide Association Studies (GWAS). Our team has successfully developed a strong pipeline of soybean germplasm with resistance to SCN or RKN and competitive yield across all maturity groups. Based on previous discoveries, many genetic populations have been developed to confirm and deploy these genes for nematode resistance. In this new proposal, this team will use an integrated conventional and advanced genomic technologies to achieve the following objectives: 1) incorporate nematode resistance genes into elite high-yielding lines to develop SCN and/or RKN resistant soybean varieties; 2) identify novel sources of multiple nematode resistance from existing resistant sources or soybean germplasm from USDA Soybean Germplasm Collections; 3) map nematode resistance gene(s) to develop DNA markers for efficient breeding selection; and 4) incorporate SCN and/or RKN resistance into high-yielding lines with value-added seed composition or other key abiotic and biotic tolerance traits. This work will benefit the entire value chain by providing new soybean varieties adapted to local growing conditions with resistance to multiple nematode species. This project will also provide new and improved materials to commercial and public breeders for use as parental stocks to develop high-yielding, nematode resistant varieties. DNA markers and QTL information generated will benefit soybean researchers, enabling marker-assisted selection and seeking understanding of the genetic mechanisms underlying nematode resistance.

Funder: United Soybean Board

Amount: $319,996

PI: Zenglu Li, College of Agricultural and Environmental Sciences

This project leverages assets from a previously funded NOAA project and the research team’s expertise in using immersive technologies to translate critical hazardous weather information with these theory-driven and evidence-based objectives: (1) amplify the impact of risk communication through mixed-reality (MR) simulations of hazardous weather events (hurricane, wildfire) that can localize the experience of risk in the user’s physical space (2) co-develop transformative action plans for emergency preparedness with key stakeholders (emergency managers, local government representatives, community members) to increase the resilience of communities at risk for hurricanes (Florida) and wildfires (Oregon); (3) develop and test AIWX, a prompt engineered to leverage the power of artificial intelligence to summarize and synthesize large volumes of weather information to assist decision-making when hazardous weather events are imminent. Through a two-year project that engages close to 600 coastal residents, emergency managers, and other stakeholders in the weather enterprise in Florida and Oregon, we aim to address Social, Behavioral, and Economic Sciences Priority (2) – Behavioral responses to hazardous weather events. We will integrate a community-based participatory research approach to work closely with key stakeholders, developing actionable weather solutions that are feasible and sustainable over time. In the Southeastern United States, University of Georgia’s research team will partner with the National Hurricane Center and the Broward County Public Library system (37 branches) in Florida. In the Pacific Northwestern United States, University of Oregon’s research team will partner with the Oregon Museum for Science and Industry in Oregon. Through collaborators who are well-established in these at-risk communities, we can leverage existing resources at the sites, rely on their ability to handle hundreds of thousands of foot traffic from community members, and draw on their reputation as a trusted source of information in the community. At the end of the project, we will deliver a library of immersive experiences that include both virtual reality and mixed reality experiences to simulate hazardous weather events with visceral sensorimotor cues, elevating risk perceptions and drawing attention. The mixed-reality prototype that is currently at RL3 will be tested and iteratively enhanced to RL7. Functionality will be demonstrated in near-real world environments and large-scale demonstrations in Florida and Oregon (tested across N = 240 participants). The co-developed community action plans (‘hero project’) will be tested through the integration of our collaborators and community partners (N = 320) to determine how community members build collective efficacy that leads to actions for transformative and sustainable community resilience against hazardous weather events (target RL5). AIWX will be tested for feasibility with emergency managers and local government personnel to eventually be integrated into their training protocols (target RL7). Together, the southeastern and Pacific northwestern areas of the United States incur billion-dollar disasters from hazardous weather events. By combining the expertise of interdisciplinary university research teams, government, trusted civic partners in at-risk communities, and leveraging the power of cutting-edge immersive technologies and AI, the proposed project aims to overcome individual and community vulnerabilities to weather and better communicate their risks to minimize preventable harms to life and property.

Funder: U.S. Department of Commerce

Amount: $391,865

PI: Sun Joo (Grace) Ahn, Grady College of Journalism and Mass Communication

For women in the United States, breast cancer is the most common malignancy and the second leading cause of death. In this application, we focus upon a specific subtype of breast cancer known as triple-negative breast cancer (TNBC). Compared to other breast cancer subtypes, TNBC is considered more aggressive and extremely difficult to treat with standard therapies. As a result, it has a high recurrence rate and a high overall mortality rate. TNBC accounts for up to 20% of all breast cancers, with a higher incidence in ethnic minority populations and young women (usually <40 years of age). Approximately 70% of patients with advanced TNBC die of disease recurrence and/or metastasis within 5 years of initial diagnosis. Therefore, there is an urgent need for the medical community to develop more effective therapeutic options for this deadly disease. In this project, we will investigate a novel experimental compound, named LG007, for its anti-cancer activity in TNBC. Of significance, we will utilize robust TNBC Patient-Derived Xenograft (PDX) mouse models to study the in vivo efficacy of LG007. Our preliminary results demonstrated that LG007 effectively inhibits TNBC tumor growth and metastasis. Notably, we found that LG007 treatment could robustly shrink large human-derived TNBC PDX tumors, with a near-complete response. These preliminary results strongly support the premise that LG007 is a novel and potent drug candidate capable of treating progressive TNBC and associated metastasis. Furthermore, we demonstrated that LG007 is able to target and regulate miR-10b, a well-known oncogenic miRNA that promotes tumor development and metastasis. Therefore, we hypothesize that miR-10b is a primary target of LG007 that is critically involved in the molecular mechanisms of action by which LG007 inhibits tumor growth and metastasis. Three specific aims are proposed in pursuit of the project’s objective to develop a new therapy for the treatment of TNBC. In Aim 1, we will determine the mechanistic roles of miR-10b and one of its targets, NR4A3, in the anti-TNBC activity of LG007. In Aim 2, we will investigate the in vivo efficacy of LG007 utilizing a variety of advanced mouse models that mimic the clinical setting of TNBC and its associated recurrence and metastasis. In Aim 3, we will characterize the pharmacological and toxicological properties of LG007 in preparation for future translation to clinical testing. We expect that the results obtained from this study will lead to the development of a novel, safe, and effective treatment for patients with advanced TNBC.

Funder: NIH

Amount: $756,324

PI: Yaguang Xi, College of Pharmacy

Groundnut (Arachis hypogaea L.) is the world’s second most produced grain legume and a critically important crop in Africa, particularly for small-scale producers and communities in the drylands. This crop represents a subsistence protein source for smallholder farming families and an affordable nutrition source in global markets, as well as a source of cash to increase household income, and is thus a driver of agricultural transformation in these areas. This crop is also an essential source of fodder for livestock in West Africa during the dry season. Groundnut’s high susceptibility to diseases creates a yield gap, compounded by limited access to fungicides in African production systems, necessitating solutions that do not depend on annual chemical inputs. Genetic resistance is the most practical and effective way for African farmers to achieve better yields. Genetic variation in peanut is limited due to its recent, unique, polyploid origin, which limits crop improvement through breeding. Wild relatives of peanut are a rich source of alleles that have arisen over millions of years of natural selection in diverse environments. However, in early generation hybrids, the valuable wild alleles are masked by the more numerous unfavorable wild alleles that confer poor growth habit, small seed size, etc. These favorable wild alleles can be discovered through multiple cycles of backcrossing and screening for favorable traits when the wild alleles are incorporated with a substantially cultivated peanut genetic background. The discovery is most complete if wild alleles are monitored by DNA markers during the backcrossing. This project focuses on identifying and transferring high-level resistance to groundnut’s four most destructive diseases in Africa: rosette virus disease, early leafspot, late leafspot and rust. The introgression of these resistance traits into groundnuts represents the core deliverable of this research initiative, offering a pathway to bridge the yield gap through enhanced genetic diversity rather than increased chemical inputs. This goal will be achieved by systematically exploring sources of germplasm for key biotic traits, validating them, and incorporating them into semi-elite donor lines. These improved lines will be transferred to the groundnut breeding networks to develop cultivars that are more resilient and productive, ultimately benefiting small-scale farmers across Africa. The project is rooted in a proven Wild Species Groundnut Improvement Pipeline developed by the University of Georgia, now deployed in collaboration with partners in West and East Africa. Our pipeline in the USA and Senegal has created several sets of new germplasm: a growing collection of backcrossed populations of groundnuts introgressed with seven different wild species and 23 wild-derived allotetraploids incorporating an extra 15 accessions of 12 different species have been created over the last 15 years and are readily available for this project. The proposed work will build on this to produce new improved groundnut cultivars that will need fewer plant protection products.

Funder: Gates Foundation

Amount: $4,998,761

PI: David Bertioli, College of Agricultural and Environmental Sciences

Duke University and the University of Georgia (UGA) propose an Industry-University Collaborative Research Center (IUCRC) called the Center for Innovation in Risk-analysis for Climate Adaptation and Decision-making (CIRCAD). CIRCAD will be an interdisciplinary, high-impact research center that integrates climate science and engineering, data science and modeling, risk assessment and decision theory, and economic and policy analysis to develop and promote innovative and actionable strategies, products, and practices that support the insurance industry in addressing climate risk. CIRCAD will recruit, mentor, and develop a diverse, highly trained, climate-ready workforce. We have identified three key challenges to the insurance industry’s ability to cost-effectively manage climate risk and catalyze society-wide climate risk reduction. First, there exists a fundamental mismatch between the typical 12-month term for individual insurance contracts and the long-term, systemic nature of climate exposures, eliminating the industry’s ability to clearly signal risk and incentivize mitigation via premiums. Second, the existing suite of climate risk models used to set insurance premiums does not adequately account for risk mitigation measures at the systems scale, thereby reducing the incentive and ability of communities to design and implement effective measures. Finally, the basic climate research and data products available today do not fulfill the decision-making needs of insurers, and there is little consistency in data reporting formats, standards, and platforms. CIRCAD’s research, coordination, and convening activities will seek to address these three challenges. Intellectual advances anticipated from the current set of projects include: (i) design, evaluation, and pilot testing of novel climate-responsive insurance solutions and risk mitigation strategies; (ii) development of methods and models for quantifying climate resilience at a systems scale, with a focus on the value of nature based solutions; and (iii) application of decision theory to the compilation, evaluation, and use of climate data and models to reduce uncertainty in risk management and investment decisions. We expect our research and engagement activities to not only support the insurance industry in its risk management role, but also stimulate complementary risk mitigation efforts by governments, businesses, and individuals. Further, dissemination of the knowledge and tools produced by this research will enhance climate risk decision-making and resilience on a national scale. In addition, CIRCAD will initiate or augment four programs that collectively span a range of workforce development stages and training needs: (i) undergraduate and master’s student team projects, (ii) master’s, doctoral, and post-doc trainee research experience and mentorship, (iii) advanced degree programs in risk engineering, climate and sustainability, and financial technology, and (iv) opportunities for shared learning between students and professionals, both in the classroom and in the workplace, including co-enrolled short courses, internships, and co-ops.

Funder: NSF 

Amount: $500,000 

PI: Marc Ragin, Terry College of Business 

A grand challenge is how cellular clocks in organisms, tissues, and cells become synchronized. The focus here will be initially on understanding the synchronization of cellular clocks in filaments in a model fungal system, Neurospora crassa. The core clock mechanism genes wc-1, wc-2, and frq have homologs in flies and mammals but are in single copy, and the clock in tissues called hyphal filaments serve as a model for the clock in tissues in other eukaryotes. There are two principal theories for how clock synchronization arises; (1) through a shared quorum sensing signal in the media between cellular clocks; (2) through cell to cell contact and communication. The goal of this proposal is to understand the synchronization of biological clocks between filaments in N. crassa. An interdisciplinary team from genetics, engineering, physics and biochemistry will tackle this challenge. Task 1: We will develop novel microfluidics platforms to measure phase synchronization of biological clocks on a controlled number of living N. crassa filaments. Task 2: We will develop and identify models of clocks in filaments using novel ensemble methods from Physics. Task 3: We will also identify and test signaling molecules that may be responsible for the synchronization by a newly developed method of Continuous In Vivo Metabolism-NMR (CIVM-NMR) biochemistry. Collective behavior is a new field of study outside the boundaries of existing disciplines. The project is transformative because it examines the origin of the clock system by pushing the scale of measurements on the clock to single clock mRNAs. We will use CIVM-NMR to link metabolites with a quorum sensing signal for the clock. We propose the following convergences: (1) identification of metabolite(s) to explain the origin of circadian rhythms in single cells; (2) a physical theory of the clock in filaments identified by methods from statistical physics; (3) and explaining the origin of the clock in the phase synchronization of single filaments. The clock is pervasive in its effects on genes to ecosystems. (1) It impacts the health of animals and plants and is being engineered for the timed delivery of biologicals, the development of algal bioreactors and crop improvement. (2) The new methods for studying cell-cell synchronization have a direct relevance to the collective behavior of animals, such as marching locusts and their control as agricultural pests. (3) The clock through its light-entrainment capability has a direct impact upon the daily transcriptome dynamics of marine bacterial assemblages and hence may impact carbon cycling in marine ecosystems. Education and outreach activities are designed around the research focus of this project, biological clocks and their synchronization. (1) An interdisciplinary research-centered course, Clock Collaboratorium, will be developed. (2) Undergraduate research projects will be developed with the central theme of biological clock and used in two NSF REU site programs. (3) we will build a collective behavior community of scientists through a Gordon Research Conference in Collective Behavior.

Funder: NSF 

Amount: $1,324,119 

PI: Jonathan Arnol, Franklin College of Arts and Sciences, Department of Physics and Astronomy 

Switchgrass, a C4 grass native to the US, is a high-yielding cellulosic bioenergy feedstock. Lowland switchgrass ecotypes produce high biomass yields but are largely cold-sensitive, which hinders expansion of their cultivation into Northern US regions where the lower yielding, but cold-tolerant upland ecotype is grown. Extensive efforts are dedicated to the rapid domestication of switchgrass, selecting for biomass yield, composition and environmental adaptation, to help meet the emerging demand for biofuels. To achieve this, a thorough understanding of the genetics of key traits and an ability to manipulate the underlying genes in a tissue or cell-type-specific manner is essential. This project aims to leverage single-cell genomics and natural variation in switchgrass to investigate mechanisms underlying cold tolerance and plant regeneration. By integrating single-cell genomics and spatial transcriptomics, we will generate a comprehensive resource detailing cell-type-specific transcripts and active cis-regulatory elements. Additionally, we are developing a cost-effective, open-source spatial transcriptomics platform specifically for plants, enabling 3D reconstruction of transcriptomes. Achieving these goals will provide the research community with a transformative resource and uncover genes and cis-regulatory elements critical for cold tolerance and plant regeneration. In the long term, this work will advance switchgrass genome annotation, improve causal gene identification for traits, refine transgene and cis-regulatory sequence design, and enhance the precision of genome-editing strategies across diverse accessions to engineer trait variation. To accomplish these goals, we propose three major objectives that will result in a high-resolution single-cell genomic atlas for switchgrass, development of open-source spatial transcriptomics applications for plants, identification of gene regulatory networks underlying cold tolerance and plant regeneration. Objective 1: Create a single-cell genomic atlas for switchgrass. Objective 2: Identify cell-type-specific transcripts and active cis-regulatory elements in upland (VS16), lowland (AP13) and isogenic switchgrass genotypes targeted at improving cold tolerance. Objective 3: Identify cell-type-specific transcripts and active cis-regulatory elements important for cell totipotency in regenerable calli as compared to non-regenerable calli. Successful completion of these objectives will result in a high-resolution and high-quality cell type-specific transcript and chromatin accessibility atlas for ten major switchgrass organs. This resource will enable the switchgrass community to multiply its impact to improve this important bioenergy feedstock. The use of single-cell genomics to explore cold tolerance and plant regeneration will provide an unprecedented view into how these processes occur at cell-type resolution thereby enabling development of varieties with expanded growth ranges, and advances in genome engineering strategies independent of genotype.

Funder: U.S. Department of Energy 

Amount: $2,183,886 

PI: Robert Schmitz, Franklin College of Arts and Sciences, Department of Genetics 

This DOE Center renewal proposal will focus on structure, biosynthesis, and function of the plant cell wall polysaccharide rhamnogalacturonan-I (RG-I), a major ubiquitous and structurally complicated pectic polysaccharide that exists in the cell walls of all vascular plants. Plant biomass is an abundant renewable resource for the production of carbon-based bioproducts, chemicals, and glycomaterials. However, due to its complexity, there are still major gaps in our understanding of the structural and molecular organization of diverse plant cell walls. Development of new analytical technologies to elucidate the structure, synthesis, and roles of RG-I in wall architecture will provide critical insights into how carbon-rich cell walls are assembled and modified. In the next funding cycle, we propose a set of complementary strategies to elucidate the structure of RG-I that address several factors that have presented challenges to the analysis of RG-I. We have developed a library of carbohydrate active enzymes for deconstructing specific linkages within cell wall polysaccharides. These enzymes will be used to obtain RG-I fragments that can be structurally characterized with spectrometric methods. A new approach that we are developing, MALDI-TOF MS fingerprinting, will allow for high-throughput screening of oligosaccharides extracted from different species and tissue types. We will also pursue both a top-down and bottom-up approach to the analysis of RG-I Chemical Structure. Cell wall matrices are made up of insoluble components that resist spectroscopic analysis. We will continue to optimize the use of ionic liquids and permethylation enabling unbiased carbohydrate analysis of intact biomass and improving the recovery of galacturonic acid and neutral sugars for analysis. We will use new advanced MS/MS and permethylated NMR methods to analyze larger RG-I fragments derived from both enzymatic synthesis and natural sources to elucidate the backbone structures and other glycoconjugates attached to the RG-I. To further our understanding of RGI biosynthesis and function, we will use the robust HEK293 cell heterologous protein expression system developed at the CCRC and previously used by us to express functional plant cell wall glycosyltransferases (GTs) to study the mechanism of RG-I backbone elongation, and the identity and characteristics of enzymes that add the glycosyl and nonglycosyl substituents onto the backbone. With the discovery of several RG-I biosynthetic activities including RG-I backbone GTs and acetyltransferases, target genes have been selected to study the biological function in model plant species. The focused technologies developed through our RGI research will address key challenges in the complex carbohydrate field. By applying these tools to understand the structure, function, and biosynthesis of difficult-to-characterize polysaccharides and glycoproteins, we will continue our expansive collaboration efforts with researchers outside our field, leading to high-quality publications. The DOE center will ensure that these techniques are disseminated with the broader scientific community through annual workforce training and workshops. Additionally, CCRC faculty and staff will mentor graduate students and post-docs in the RGI research program. Through extensive outreach and collaboration, these cutting-edge technologies will be accessible to the scientific community.

Funder: U.S. Department of Energy 

Amount: $2,805,000 

PI: Parastoo Azadi, Complex Carbohydrate Research Center 

Familial Dysautonomia (FD) is a severe genetic disorder affecting children, with no specific treatment. It involves neurodevelopmental defects at birth and progressive sensory and autonomic neuropathy. Symptoms include progressing loss of pain and temperature sensation, gait ataxia, and blindness. FD is caused by a mutation in the ELP1 gene, reducing the Elp1 protein in peripheral neurons specifically; but decades of research on ELP1 have not yet yielded a treatment. Especially important, a post-birth treatment is needed to prevent further neuron loss. Thus, exploration of alternative treatments, like targeting the extracellular matrix (ECM) are crucial. This R01 renewal application follows a successful project that assessed the molecular mechanistic basis of disease severity in FD and aimed at personalized therapies for FD. There, we discovered genipin, a compound of a Traditional Chinese Medicine, which has shown promise in preventing neurodevelopmental defects and sensory neuron death in FD by crosslinking ECM proteins. Our goal is to investigate genipin’s mechanism of action and its potential to prevent FD-related peripheral neuropathy in human and mouse models. Using transcriptomics and proteomics analysis, we found the ECM and glycosaminoglycans (GAGs) downregulated and growth factors upregulated in FD, possibly a compensation mechanism. Here, we will test if the ECM and GAGs are aberrant in FD, using deep disaccharide analysis. We will assess if this consequently leads to aberrant growth factor presentation and signaling issues, preventing proper development of sensory neurons — and whether genipin’s crosslinking action rescues that (Aim 1). We will assess genipin’s ability to prevent neurodegeneration in a human FD stem cell model, focusing on axon growth, cytoskeletal, and energy issues (Aim 2). Finaly, we will evaluate genipin’s effect on the FD mouse model, testing for phenotype reversal and sensory neuron preservation (Aim 3). The outcomes could position genipin as a treatment for FD and other peripheral neuropathies, as there are currently no FDA-approved drugs targeting these conditions.

Funder: NIH 

Amount: $2,950,014 

PI: Nadja Zeltner, Franklin College of Arts and Sciences, Department of Biochemistry and Molecular Biology