Category: Notable Grants

The overarching goal of the proposed research is to fill key science gaps in the understanding of smoke production and its physicochemical properties, as well as the evolution of these properties during atmospheric aging, to better understand the effects of smoke on health and visibility. Filling the major gaps in understanding smoke production in prescribed fires is essential for optimizing the use of prescribed fires in a manner that maximizes ecosystem health, prevents wildfires, and minimizes smoke impacts. This applies to DoD lands, where improving the health and safety of installation personnel and surrounding communities is a priority. This research aims to link smoke emission rates, physiochemical properties, and evolution during atmospheric processing to burn conditions. Objectives include: (1) performing combustion experiments using representative surface fuels and forest floors collected from DoD lands; (2) implementing an experimental matrix that dissects the effects of fuel moisture content, relative humidity, and the existence of duff on smoke production; (3) quantifying emission factors of key smoke components; (4) characterizing the smoke chemical composition, optical properties, and water uptake potential; (5) simulating atmospheric processing of the smoke; (6) deriving parameterizations that link smoke production and physicochemical properties to fire behavior; and (7) using the experimental results to refine and extend smoke production calculations in QUIC-Fire. This research will produce knowledge that links fuel bed composition, fuel moisture content, and relative humidity to fire behavior and the production rates of key smoke components. Incorporating these experimental results in QUIC-Fire will provide land managers with an improved tool to investigate the tradeoffs between different ignition strategies in achieving desired fire behavior and minimizing smoke impacts. Furthermore, the knowledge that will be produced by this research on linking smoke chemical composition, microphysical properties, and atmospheric processing to burn conditions will be of benefit to the atmospheric chemistry community. The speciated smoke emission factors will improve wildland-fire emission inventories used in air quality models.

Funder: U.S. Department of Defense 

Amount: $2,539,175 

PI: Rawad Saleh, College of Engineering 

In all domains of life proteins are modified via glycosylation. This addition of sugar molecules to proteins is critical for their folding, function, and recognition by their partners. Rigorous studies have shown that in well-studied eukaryotic organisms, proteins synthesized in the endoplasmic reticulum (ER) are glycosylated on asparagine residues as well as on serine or threonine residues. These modifications are critical for the trafficking of proteins in the secretory pathway. Protein glycosylation acts as a marker for protein folding to ensure only folded and functional proteins are sent from the ER. Once outside the ER, glycans on proteins also act as critical recognition motifs to route proteins accurately to their correct subcellular location. These glycan-centric mechanisms are found in almost all well studied eukaryotes. Surprisingly, the intracellular eukaryotic parasite, Plasmodium falciparum, does not appear to utilize any of these canonical protein glycosylation-based mechanisms to traffic proteins in its secretory pathway. This parasite causes malaria, and the clinical symptoms of malaria are a direct result of its growth and expansion with human red blood cells (RBC). The parasite depends upon protein secretion to ensure its survival within the RBC. Even though glycan modifications on proteins are a major driver of immune responses, we do not know if and how P. falciparum glycosylates proteins in its secretory pathway during the clinically relevant asexual blood stages. In fact, the P. falciparum genome lacks several genes in this pathway that are well conserved in other eukaryotic organisms, including other closely related parasites. To fill this major gap in our knowledge, we will combine genetic and cellular assays to study if conditional knockdown of the targeted glycosyltransferases inhibits protein trafficking within the highly branched and unconventional secretory pathway of P. falciparum. Our preliminary data show that the parasite protein glycosylation pathway genes are essential for parasite growth within the RBC. The experimental approach will test if protein glycosylation also functions in an unconventional protein quality control pathway in the parasite ER. We will utilize glycoproteomic approaches to determine the landscape of protein glycosylation during the intraerythrocytic growth of P. falciparum. The collaborative research team will combine these proteomic approaches with genetic tools to determine which glycosyltransferases are responsible for which the glycan modifications. The specific glycosyltransferase activities will be validated using complementation assays as well as in vitro assays using recombinantly expressed glycosyltransferase. The tools and reagents developed for this project may find wider applicability in glycobiology and parasitology. Given the importance of glycans in driving the host immune system, the proposed studies may have important implications for our understanding of the antimalarial immune response.

Funder: National Institutes of Health 

Amount: $3,370,111 

PI: Vasant Muralidharan, Franklin College of Arts and Sciences, Department of Cellular Biology 

Cryptococcal meningoencephalitis (CME) is responsible for more than 15% of the total deaths of AIDS patients. The disease claims hundreds of thousands of lives each year, with global mortality rates of ~70% despite antifungal therapies. Unfortunately, there is no vaccine clinically available for cryptococcosis. The challenges of preventing and treating this fungal disease motivate our investigation of cryptococcal pathways that can induce a strong protective host response. The encapsulated fungus Cryptococcus neoformans is known to undergo yeast-to-filament morphological transition. We previously showed that morphotype of this fungus has a profound effect on its interaction with various hosts. In mammalian models of cryptococcosis, the yeast form is pathogenic while the filamentous form is not. We established that the transcription factor Znf2, which drives filamentous growth, is a powerful anti-virulence regulator. Cryptococcal cells overexpressing ZNF2 (ZNF2oe) are avirulent and elicit strong and long-lasting protective immunity, which serves as an effective vaccine against subsequent lethal challenges. Importantly, we showed that once mice are vaccinated with ZNF2oe cells, their CD4+ T cells are dispensable for protection at the time of fungal challenge (mimic people with HIV prior to AIDS). Furthermore, vaccination with ZNF2oe cells even in hosts with pre- existing CD4+ T cell deficiency is also protective against cryptococcosis (mimic AIDS patients). These findings are important because the majority of cryptococcosis patients are AIDS patients with low CD4+ T cell counts, and our preclinical studies suggest that cryptococcal vaccines could be effective in these individuals. The long-term goal of this project is to characterize the filamentation pathway and explore it for therapeutics (e.g. vaccines). We have made significant progress in establishing the link between morphotype, virulence and immunity, and discovered multiple regulators required for both Znf2-directed filamentation and Znf2-induced host immunity. Recently, we also identified mutations that block Znf2’s function in filamentation, but do not affect its ability to induce host protective effects. These findings provide a unique opportunity to pinpoint cryptococcal factors associated with host protective effect of Znf2. Because ZNF2oe in both heat- inactivated and live cells provides host protection, we predicted that extracellular components of ZNF2oe cells are important protective immunogens. Consistently, host protection elicited by ZNF2oe cells depends on the capsule where extracellular antigens are localized. Additionally, our preliminary data revealed that some antigens are secretory proteins including several glycosylphosphatidylinositol (GPI)-anchored glycoproteins. Capitalizing on these discoveries and our expertise in mRNA lipid nanoparticle (mRNA-LNP) technology, we aim to (1) define cryptococcal factors that are important for Znf2’s anti-virulence effect; (2) identify immunogens that elicit protective host responses; and (3) use selected immunogens to develop mRNA-LNP or recombinant protein vaccines against cryptococcosis.

Funder: National Institutes of Health 

Amount: $2,828,534 

PI: Xiaorong Lin, Franklin College of Arts and Sciences, Department of Microbiology 

This project will investigate (a) how to meaningfully incorporate playful elements into the foundational secondary and undergraduate mathematics topics of algebra and calculus, and (b) the potential outcomes of “playifying” classroom mathematics for students’ learning and enjoyment. Motivation and engagement are critical factors in supporting students’ abilities to understand and persist in mathematics and the STEM fields. Mathematical play offers opportunities for students to exercise agency and engage in authentic disciplinary practices, and studies of mathematical play show positive outcomes for engagement, enjoyment, and learning. However, the current research base is largely situated in either the preschool / elementary grades or in out-of-classroom settings, with a dearth of studies addressing how to incorporate play into classroom mathematics, particularly at the secondary and undergraduate levels. The proposed project will address this gap by characterizing mathematical play for adolescents and undergraduate students, examining how to foster it, and systematically studying its learning benefits. The project will implement a multi-phase design experiment model, leveraging clinical and stimulated recall interviews, small-scale teaching experiments, and whole-class teaching experiments, with each phase building on the findings of the prior. The research activities will produce a set of findings about the aspects of task design, instruction, and classroom interactions that support mathematical play, as well as the learning benefits of mathematical play for adolescents and undergraduates.

Funder: National Science Foundation 

Amount: $804,347 

PI: Amy Ellis, Mary Frances Early College of Education 

The proposed activities will enhance understanding of how genes from microbial ancestors can evolve to operate in a eukaryotic genome to produce a new beneficial trait. Expected results are significant to discerning patterns of molecular evolution that lead to evolutionary leaps and phenotypic novelty given the large amount of genetic material from foreign entities entering eukaryotic genomes. Extending our findings to a comparative evolutionary framework has the potential to transform how we think about the evolution of biological complexity from microbial traits at a molecular genetic level by focusing on comparing and contrasting the processes that have been co-opted to control expression. Proposed broader impact activities will increase diversity of undergraduate and graduate students identifying with groups underrepresented in biology, contribute to development and support of a diverse and globally competitive workforce, and increase public scientific literacy. The PIs will build a network of undergraduates, graduate students, and postdocs from UGA and other institutions in the southeastern US who are interested in insect-microbe research, which will be used for promoting career opportunities, increasing awareness of research, and create connections between people and institutions.

Funder: National Science Foundation 

Amount: $1,222,664 

PI: Gaelen Burke, College of Agricultural and Environmental Sciences, Department of Entomology 

Degenerative photoreceptor (PR) cells contribute to vision loss in AMD patients. The lack of effective models to study PR repair and maintenance is a critical gap in our knowledge, limiting current therapeutic strategies to prevent retinal damage and reinstate vision in AMD. Previous data revealed an ATF6-dependent loss of cone PR outer segments (OS), correlated to dysfunctional mitochondria and loss of critical ciliogenesis genes. While ATF6’s role in mitochondrial health and OS formation is not characterized, its pharmacological modulation shows promise in repairing cone PR function in AMD. We hypothesize that that ATF6’s transcriptional network directly regulates cone PR OS formation by improving mitochondrial health and upregulating essential ciliogenesis genes. We aim to define ATF6-dependent mitochondrial defects in AMD relevant retinal cell types (RPE, PR, RGC, Müller glia) and investigate changes in mitochondria morphologies and function (Aim 1.1). ATF6-dependent targets, such as RAB23, MARS2, OPA2, which have a critical role in mitochondrial stability, will be confirmed through biochemical and molecular analysis. Using ATF6 control and mutant retinal organoids, we will evaluate ciliogenesis components and perform rescue experiments using ATF6 activators to elucidate their therapeutic potential (Aim 1.2). Electron and confocal microscopy, along with patch clamp recordings, will assess functionality in newly generated cone PR cells. Aim 2; using the bi-foveated, cone-rich brown anole lizard, we created atf6 Mutant lizards, confirming the absence of cone PR OS. Advanced imaging will examine cone PR OS and foveal morphology. Retinal analysis includes a characterization of all AMD-affected cell types through biochemical and molecular data collection, with bulk RNAseq analysis in progress (NovoGen). The atf6-dependent rescue of lizard cone PR OS’s in Mut animals will be assessed through micro-injection of AV[atf6(N)] into the intravitreal space. Strong collaborations assist with OCT, AOSLO images, and ERG readings. Our research combines stem cell technologies and the lizard model to explore an alternative regulatory mechanism for cone OS development and regeneration using the ATF6 transcriptome. Alongside current AMD therapies like RPE cell replacement, our project offers a potentially synergistic approach to treat AMD pathologies.

Funder: Brightfocus Foundation

Amount: $449,986

PI: Heike Kroeger, Franklin College of Arts and Sciences, Department of Cellular Biology

The health impact of food processing is a relevant and timely topic in human nutrition as processed food constitutes a large part of the world’s food consumption. Approximately 60% of food in the US and UK is ultra-processed. The term ultra-processed food indicates formulations generally including five or more ingredients, mostly of cheap industrial sources of dietary energy, nutrients, and additives, using a series of processes to manufacture, and containing minimal whole foods. In humans, a direct association has been found between consumption of ultra-processed foods and specific diseases such as cardiovascular disease, obesity, neurodegenerative disorders, etc. and with all-cause mortality. Advanced glycation endproducts (AGEs) and advanced lipoxidation endproducts (ALEs) represent classes of pro-oxidants in foods, the presence of which is promoted by food processing at high temperatures. A large body of evidence supports that AGEs are involved in the pathogenesis of diseases and their complications. Dietary AGEs are linked to excess radical oxygen species, high oxidative stress, cytokine synthesis, and inflammation which can cause obesity, cancer, neurodegenerative disorders, osteoarthritis, chronic kidney disease, and other diseases. Many commercial dog foods by definition are ultra-processed in that they include more than five ingredients, are manufactured using a series of processes, and containing minimal whole ingredients. In one study evaluating dog and cat foods, it was estimated that on a metabolic body weight basis compared to humans consuming a high ultra-processed Western diet, dogs consume approximately 120 times and cats approximately 40 times the amount of AGEs on average daily.

The objectives of this study are to evaluate the influence of food processing using three diets that are identical in composition but processed in three different ways. We hypothesize that dogs that consume a minimally processed diet when compared with highly processed diets will show lower dietary AGEs, plasma AGEs, urinary AGEs, urine protein-to-urine creatinine ratios, blood glucose, serum insulin, serum fructosamine, receptors for AGEs, and plasma inflammatory biomarkers. Thirty clinically healthy dogs that are relatively age-matched will be fed a standard dry (kibble) diet for 4 weeks. They will then be randomized into one of three diet groups for 8 weeks, and samples will be collected at the end of this period. Comparisons will be made between diet groups and between the start and end of the treatment period.

Funder: The Farmer’s Dog

Amount: $521,419

PI: Joseph Bartges, College of Veterinary Medicine

Beginning in 2020, the Georgia Department of Community Supervision (DCS) has implemented a person-centered supervision (PCS) model for officers. This model seeks to meet the dual roles of DCS for accountability and rehabilitation by enhancing the voices of persons on probation and parole while under supervision through relying on elements of procedural justice, technology, and evidence-based research in communities across Georgia. Given the scale of the PCS model, there is a need to develop an instrument to consistently assess the quality and outcomes associated with PCS throughout the state, to ensure the model is effective and delivered in an appropriate manner. The first goal of this proposed evaluation will be to establish an internal instrument to assess PCS program quality across all 51 judicial districts in the state of Georgia. Instrument development will be conducted in four stages (1) collaborative, systematic examination of existing assessment instruments and related documents that may capture PCS practices relevant to the state of Georgia, (2) Pilot testing and refinement, (3) Instrument demonstration and (4) Instrument validation. Additionally, to our knowledge, no systematic exploration of how the PCS model relates to criminal justice and public safety outcomes currently exists. Thus, the second goal of this evaluation proposal is to examine outcomes of the PCS model in the State of Georgia using existing data provided by the Georgia Department of Supervision and other publicly available data. The results from the proposed evaluation will assist DCS in establishing an evidence-base for the PCS model as well as provide a solid foundation for future internal assessment throughout the state.

Funder: Georgia Department of Community Supervision

Amount: $661,139

PI: Orion Mowbray, School of Social Work

Livestock integration can restore synergies between animal and plant agriculture, long the cornerstones of sustainable farming. For example, pastured chickens (Gallus domesticus) might feed heavily on pests and weeds while generating nutrient-rich manure, benefiting crops. But chickens also might eat beneficial predatory, detritus-feeding or pollinating arthropods, or spread harmful bacteria (e.g., Campylobacter, Salmonella) that endanger food safety. Unfortunately, there have been surprisingly few holistic studies of pastured chickens’ ecological roles, both good and bad, on highly diversified mixed-vegetable farms. This leaves growers unable to predictably weigh the benefits and risks of crop-chicken integration. Working in cooperation with our grower collaborators, we propose to: (1) Detail chickens’ feeding on pest and beneficial insects, and weeds, through molecular analysis of dietary-DNA remains in chicken feces, (2) Track likely sources of chicken exposure to Salmonella and Campylobacter bacteria using whole-genome pathogen sequencing, and (3) Quantify the birds’ net impacts on arthropods, weeds, and soil microbes, through on-farm chicken exclusion experiments. Our “Chicken Dinner” outreach effort will recruit grower citizen-scientists from across the southeastern U.S. to submit samples from their own pastured flocks for diet and pathogen analysis, so they can assess the ecosystem services (and disservices) their birds are providing. Our ultimate goal is to provide growers with practical tools to maximize the benefits of pastured chickens, while minimizing any dangers, as part of whole-farm planning. We address both Sustainable Agroecosystem priorities by developing new approaches to significantly increase several ecosystem services, while improving managed system biodiversity and sustainability.

Funder: USDA NIFA

Amount: $749,434

PI: William Snyder, College of Agricultural and Environmental Sciences, Department of Entomology

Impulsivity refers to the propensity toward rapid action without forethought of the consequences and devaluing rewards that are delayed in time in favor of immediate gratification. Food impulsivity is associated with obesity and binge-eating disorder and can counter efforts to make healthy food choices. Regions of the brain that regulate food impulsive behaviors, such as the hippocampus and medial prefrontal cortex (mPFC), undergo neuroplasticity during adolescence and emerging evidence indicates that hippocampal-dependent memory is vulnerable to the deleterious impact adolescent consumption of “Western diets” (WD) high in saturated fat and added sugars. Furthermore, hippocampal dysfunction associated with adolescent WD consumption is not easily reversible by switching to a healthy diet during adulthood. We propose that adolescent consumption of a WD impairs hippocampal development leading to increased impulsive eating behavior during adulthood. Our unpublished preliminary data are consistent with this hypothesis and show that female rodents fed a WD during adolescence have increased impulsive actions when responding for a palatable food reinforcer during adulthood. Proposed work will extend this model to males and will also determine whether females and males on a WD during adolescence show a propensity to select smaller and more immediate food rewards over waiting for a larger payoff (delay discounting test of impulsive choice). Our additional preliminary in vivo calcium imaging data reveal differential calcium dynamics in the ventral CA1 hippocampus (vCA1) prior to impulsive vs. non-impulsive food-directed action, with analogous effects observed in the nucleus accumbens shell (ACBsh). Building off these

findings, we propose to determine how specific hippocampal circuits (vCA1->mPFC and vCA1->ACBsh) known for their role in modulating reward behaviors, inhibitory control, and impulsivity, are impacted by an adolescent WD consumption in rats. To determine whether behavioral intervention can reverse the long-lasting increased food impulsivity associated with adolescent WD, we will also investigate whether aerobic exercise, which is known to attenuate WD-induced hippocampal-dependent memory impairments, can attenuate adolescent WD-induced food impulsive actions and choices. Further, we have previously shown that the incretin hormone glucagon-like peptide-1 (GLP-1) acts on a vCA1->mPFC pathway to reduce food impulsive behavior. Thus, here we propose to determine whether clinically relevant FDA-approved GLP-1 analogue treatment reverses or attenuates adolescent WD-induced food impulsive behaviors. This proposal is sufficiently powered to determine sex differences for all experiments, and results from these studies will provide a critical contribution to obesity developmental neuroscience research and advance our understanding of how diet impacts eating behaviors.

Funder: National Institutes of Health

Amount: $3,583,438

PI: Emily Noble, College of Family and Consumer Sciences