Author: orandall

Using new ocean observing technologies in two contrasting locations, this research is combining measurements of biological and environmental conditions to understand highly productive ocean shelf food webs. Within marine food webs, a diverse community of small animals, referred to collectively as zooplankton, serve as prey for larger animals including fishes and marine mammals. Zooplankton can also influence lower trophic levels, such as marine microbes that in turn, affect nutrient and gas cycling throughout the oceans. This project is also supporting graduate and undergraduate students, including several from Savannah State University, a Historically Black University with undergraduate and graduate programs in marine sciences. The field research is providing authentic oceanographic experiences for K-12 educators, who will participate in the planned research cruises, as well as research opportunities for juniors and seniors at a local high school with high enrollment of groups underrepresented STEM. Public outreach includes annual open house events at the University of Georgia’s Skidaway Institute of Oceanography. 
 
This project addresses fundamental questions in ocean sciences regarding how environmental conditions affect the structure and composition of zooplankton communities in continental shelf ecosystems. Biologically productive shelf ecosystems can oscillate between extremes of vertically mixed waters during windy and colder seasons and vertically stratified waters during warmer and calmer conditions. Warm, calm conditions favor the formation of dense layers or aggregations of plankton and particulate material, generating hot spots of biological activity that potentially allow marine organisms to feed at much higher rates than water-column-average abundances might suggest. Although physical mechanisms of layer formation and plankton groups associated with them have been described in several shelf environments, less is known about the influence of layers on zooplankton community composition and trophic transfer. For fast-reproducing pelagic tunicates such as salps, pyrosomes, appendicularians, and doliolids, these layers or aggregations may serve as rich food resources that prime pelagic tunicates to form dense blooms which then ultimately serve as food for gelatinous predators. This sequence of events, from layer formation to pelagic tunicate reproduction and predation on the bloom, may generate high abundances of gelatinous organisms throughout the marine food web. The investigators will test this hypothesis by measuring fine-scale abundances of gelatinous zooplankton with in-situ imaging, gelatinous zooplankton diets using molecular gut content analysis, and food web properties using compound-specific stable isotopes in both vertically mixed and stratified conditions. To determine if food web interactions are generalizable to water columns with and without vertical structure, these processes will be compared in the South Atlantic Bight and northern Gulf of Mexico shelf ecosystems. Both provide favorable conditions for doliolid blooms yet differ in drivers of vertical stratification.

Funder: National Science Foundation

Amount: $1,444,777

PI: Adam Greer, Franklin College of Arts and Sciences, Department of Marine Sciences

Loss of oligodendrocytes gives rise to demyelination, ultimately resulting in axonal degeneration and debilitating clinical outcomes in diseases like Multiple Sclerosis. While remyelination can prevent neurodegeneration, there are currently no approved therapies for promoting remyelination. Thus, there is an urgent need to identify factors that control remyelination. Neural stem cells in the adult subventricular zone are one of the sources of remyelinating oligodendrocytes. These cells are a heterogeneous population that show diverse responses to signaling pathways in the healthy vs demyelinated brain. We have studied one such pool marked by Gli1, which generates remyelinating oligodendrocytes only in response to demyelination. Our previous work showed that the recruitment and differentiation into oligodendrocytes leading to functional recovery is increased substantially by loss of Gli1 in this pool of neural stem cells; however the molecular mechanisms involved in this repair is not known. Through a transcriptomic analysis comparing gene expression in neural stem cells with and without Gli1 expression, we identified the TGFβ1 pathway as a major regulator of remyelination mediated by neural stem cells. However, the effects of TGFβ1 signaling are context dependent and differ with the cell-type, timing and dosage suggesting the presence of specific modulators of the pathway in different cells. Using a combination of bioinformatic analysis and remyelination studies in mice, we discovered a novel mediator of the TGFβ1 pathway, Gpnmb which is highly expressed along with its receptor CD44 in neural stem cells in response to demyelination. In the first aim, we will define the cell-autonomous function of Gpnmb in neural stem cells and its role in remyelination by neural stem cells. In the second aim, we will determine the impact of paracrine Gpnmb signaling through CD44 receptor on remyelination mediated by neural stem cells. In the third aim, we will elucidate the mechanisms of regulation of Gpnmb by TGFβ1 ligand and reciprocal modulation of the TGFβ1 pathway by Gpnmb. For the remyelination studies, we will use the toxin induced models of demyelination. To define the molecular mechanisms of the TGFβ1-Gpnmb signaling pathway, we will utilize in vitro neural stem cell cultures from adult mouse brain. Together, these studies will help identify therapeutic targets for promoting remyelination.

Funder: National Institutes of Health 

Amount: $1,900,090 

PI: Jayshree Samanta, College of Veterinary Medicine 

This effort will produce accurate and contemporary population estimates for the South Georgia bear population. Such an estimate will allow for an evaluation of how current and future proposed harvest rates will impact the SGP. Data collection will include genetic hair-snare sampling, camera-trapping efforts, and GPS collaring activities. Together, this will provide information on black bear survival, reproduction, recruitment.

Funder: Georgia DNR 

Amount: $3,009,502 

PI: Michel Kohl, Warnell School of Forestry & Natural Resources 

A wide range of plants are grown for food, feed or fuel, and biotechnology has the potential to improve the quality, yield, and sustainability of these plants. Biotechnology applications include improving nutrition, enhancing resilience to stress, carbon sequestration, production of bioplastics/biomaterials/bioproducts/biofuels, and space exploration. Yet, technology barriers currently prevent construction of plants with complex new features. This project will generate a novel, first-of-its-kind platform – a chassis – that will enable the design and fabrication of plants with novel properties. These properties include 1) the production of high value chemicals such as pesticides, bio-materials, bio-plastics, and pharmaceuticals, 2) improved carbon sequestration to address excess global carbon dioxide levels, 3) enhanced sustainability such as the reduced need for fertilizer or insecticides and 4) improved resiliency and adaptation to drought and temperature stress. To encourage participation in science and to convey to a younger generation that science can address global challenges, this project will directly engage undergraduates in the characterization of the chassis. To broaden the diversity of participants in science, this project will recruit and train members of under-represented groups in emerging biotechnology and computational methods, thereby aiding development of a 21st century workforce in scientific disciplines. In the 21st century, the nexus of genomics and biotechnology will be the development of plants with improved yield, nutrition, and market quality, enhanced resilience to biotic and abiotic stressors, increased sustainability, and/or novel phenotypes such as the ability to sequester carbon or synthesize bio-products, biomaterials, and new-to-nature molecules. To achieve this “Third Green Revolution” in agriculture, we need the ability to engineer complex pathways and processes to harness the sustainable production platform of plants. Development of minimal bacterial and yeast genomes have permitted the rewriting of genomes and enhanced the utility of engineered microbes for biotechnology. Advancing plant genome engineering methods and resources are essential for plants to be utilized as sustainable platforms in the bioeconomy. One barrier to either singly or combinatorial engineering complex metabolic pathways and developmental processes is the sheer redundancy of gene function due to whole/segmental genome and gene duplication in all angiosperms. This project will develop a gene editing platform at scale that will be used to generate novel plant genotypes with reduced gene content and redundancy, which can serve as chassis (i.e., a platform) to rapidly engineer plants with new phenotypes and test heterologous genes relevant to biological processes of interest. This project will be the first phase in creating a true minimal plant genome, such that we can begin to rewrite the genome for new-to-nature molecules and biological processes. Due to its small stature, rapid life cycle, and amenability to transformation, the logical choice for creating a minimal plant genome is Arabidopsis thaliana, the mouse-ear cress. Our specific aims include a design phase and two cycles of build-test-learn in which we target 324 protein-coding genes for deletion across 18 5 Mb modules that span the Arabidopsis genome using state-of-the-art multiplexed gene editing approaches. The presence of synthetic lethal pairs will be tested through pairwise and higher order crosses of the modules. Machine learning approaches will be used with empirical and bioinformatic data to develop and improve models that predict gene dispensability. This project will include a Vertically Integrated Project in which all personnel are engaged across the project and institutions and in which a larger number of undergraduates can participate via a custom course entitled Building a Minimal Plant Genome to Enable a Sustainable Bioeconomy. This project will engage under-represented groups to advance participation in STEM disciplines relevant for the 21st century.

Funder: National Science Foundation 

Amount: $999,995 

PI: Carol Buell, College of Agricultural and Environmental Sciences 

The evolution of mating system, whether a plant primarily self-fertilizes (inbreeds) or outcrosses (is pollinated by a different individual), is one of the most frequent changes during plant evolution. Self-fertilization is associated with a common set of changes in floral development, together known as the selfing syndrome. For example, flowers of self-fertilizing species tend to be smaller and unscented because they do not need to attract pollinators. We know less about how the transition to self-fertilization impacts the genome and epigenome, the pattern of chemical modifications that control the way genes function. Using multiple plant species in two genera (Capsella and Mimulus), this research will investigate how genomes and epigenomes differ between self-fertilizing and outcrossing species. This work will help us understand hybridization barriers, which limit our ability to make inter-species crosses for breeding improved crops. This research will also increase our fundamental understanding of seed development, a critical aspect of agricultural productivity, and generate a wealth of sequence-based resources that will enable the plant genomics community to answer further questions. Research from this project will be incorporated into undergraduate and graduate courses taught by the PIs. Finally, this research will help maintain ongoing collaborations with local K-12 teachers to develop hands-on plant biology activities for use in their classrooms. Selfing fundamentally alters the nature of genomic conflicts and is predicted to affect several epigenetic phenomena, including genomic imprinting, effective ploidy, and host defense against transposons. RNA-directed DNA methylation (RdDM) plays a key role in epigenomic regulation and has been linked to genomic conflicts, suggesting that the nature or function of RdDM might be altered following the evolution of selfing. This project will test the hypothesis that there is a common pattern of epigenomic change following the transition to inbreeding and that these changes are mediated by RdDM. Because the selfing syndrome is only apparent when multiple transitions to selfing are compared, the relationship between mating system and the epigenome will be investigated using six inbreeder/outbreeder comparisons in two genera (Capsella and Mimulus). Specific areas of research include 1) determining how selfing impacts RdDM’s role in transposon defense and collateral gene silencing, 2) establishing the molecular cause of divergence in effective ploidy and determine whether these changes are common during the transition to selfing, 3) assessing the differential function of RdDM following the evolution of selfing and 4) determining whether there is a reduced role for RdDM in selfing species.

Funder: National Science Foundation 

Amount: $1,051,557 

PI: Andrea Sweigart, Franklin College of Arts and Sciences, Department of Genetics 

The Institute for Resilient Infrastructure Systems will conduct two case studies (one in each of the Colorado and Mississippi River Basins), develop a curriculum and certificate for natural infrastructure workforce development and host a design workshop to explore and create an implementation plan to expand the Network for Engineering With Nature to include resilience liaisons.

Funder: Walton Family Foundation 

Amount: $1,394,387 

PI: Clifton Woodson, Franklin College of Arts and Sciences, Department of Marine Sciences 

The species composition of microbial communities determines the impact they have on human health and the environment, but we have a very limited understanding of how microbial communities form. A major driver of this composition is a competition among microbes that is mediated by naturally produced antimicrobial compounds, that help shape which microbes are included or excluded from the community. Notably, many key microbes found in these communities are sensitive to the natural antimicrobial compounds produced therein. This is especially true for fungi, which are particularly vulnerable to many classes of toxic antifungal compounds produced within microbial communities. Despite this, fungi play key roles in host-associated microbial communities for plants, animals, and humans. In order to explain how such sensitive organisms gain access to antimicrobial replete spaces, my lab discovered a class of microbial interactions whereby bacterial members of the community that are resistant to antimicrobial compounds extend protection to physically associated fungal partners. Such bacterial partners act as “toxin sponges,” sequestering natural antimicrobial compounds, in addition to providing protection against frontline antifungal drugs used clinically against fungal pathogens. The discovery of bacterial partners protecting their host fungi provides an unstudied avenue that can be applied to A) predicting how microbial communities form and B) dissecting new mechanisms of resistance to antifungal drugs whereby resistance originates from a bacterial partner. My lab focuses on developing a model system based on this type of symbiosis, making use of a co-isolated fungal-bacterial pairing. The fungus, Aspergillus calidoustus, was found physically associated with a novel bacterium we named Paraburkholderia edwinii. We have rendered the bacterium genetically tractable and are working to do the same with the fungus. We are interested in discovering the mechanisms at work for protection on three levels. First, at the level of the bacterium, we are characterizing how the bacterium processes and detoxifies antifungal compounds. Second, at the level of the bacterial-fungal interface, we are interested in understanding how signals of fungal stress are communicated to the bacterium to activate the protection response. Finally, at the level of the mixed bacterial-fungal co-colony, we are focused on understanding how antifungal drug flow is manipulated through the fungal mycelial structure to bacterial aggregates that form within where detoxification of the drugs occurs. Beyond the mechanisms involved in this pairing, we aim to co-isolate bacterial-fungal pairs from clinical samples to identify which bacterial members of microbial communities provide safe harbor for associated fungi, and to what classes of antifungal compounds such partnerships can defend against.

Funder: National Institutes of Health 

Amount: $1,842,220 

PI: Kurt Dahlstrom, Franklin College of Arts and Sciences, Department of Microbiology 

Upwards of 3.8 million concussions occur annually in the United States. Only 44% of concussed individuals reduce their driving at any point following injury despite emergent concerns over post-concussion driving safety, documented driving impairment and reports of feeling unsafe driving after a concussion. Most concussed individuals who reduce their driving only do so for 24 to 48 hours following the injury. Driving is a highly complicated activity that requires visual, motor and cognitive skills, which are commonly impaired after concussion. Concussed individuals cross the centerline more frequently within 48 hours of injury and present with poorer vehicle control throughout the full symptom recovery. Yet, the time course of post-concussion driving impairment has not been characterized. There is a critical need to 1) determine when concussed individuals should return to driving and 2) identify the key concussion assessment predictors of readiness to return to driving. In the absence of formal recommendations, impaired concussed drivers are at risk to themselves and others on the road. The first specific aim is to compare simulated driving between concussed individuals and non-concussed yoked matched controls across five longitudinal timepoints (pre-injury baseline, day two, day four, asymptomatic and unrestricted medical clearance) and daily naturalistic driving from day two to day nine. Driving recommendations must be appropriate and necessitated by concussion impairments, since excessively strict recommendations wrongfully strip concussed patients of their independence and may dissuade individuals from seeking medical care. The second specific aim is to identify widely used concussion assessment outcomes that predict simulated driving performance among concussed individuals throughout concussion recovery. To address these aims, 100 concussed and 100 yoked matched control young adult college athletes will complete a simulated driving assessment and a robust concussion assessment battery at pre-injury baseline, day two, day four, asymptomatic and unrestricted medical clearance. Naturalistic driving (measured with in-car global positioning systems) will be captured from day two to day nine (seven days total). This study will determine the acute and subacute time course of post-concussion driving impairment and determine key predictors of post-concussion driving performance. Results from this innovative approach will have a broad and positive impact that will improve the safety of both concussed individuals and the general population, guide the practices of health professionals, inform the future work of researchers and substantiate the work of policy-makers by providing evidence-based recommendations for managing post-concussion driving.

Funder: National Institutes of Health 

Amount: $2,385,761

PI: Julianne Schmidt, Mary Frances Early College of Education 

Mesenchymal stromal cells (MSCs) are isolated from bone marrow and fat cells. While they are not stem cells, they exhibit a similar ability to differentiate into many types of cells. That ability forms the basis for developing treatments for a variety of diseases. MSCs also generate extracellular vesicles (EVs). The EVs transport bioactive molecules that prompt cellular-level responses. It is difficult to manufacture EVs reproducibly. This limits its current therapeutic potential. Changes in local conditions impact MSC-EV production and function. Understanding those impacts is the focus of this project. The project will also promote STEM participation of students from underrepresented groups. Many challenges contribute to the lack of successful MSC-EV clinical translation. MSC heterogeneity is a key issue. There are no effective critical quality attributes (CQAs) that predict how a given batch of EVs will perform. There are also no standardized manufacturing approaches for EVs. In addition, there is a knowledge gap regarding the effects of scaling EV manufacturing with respect to 2D vs. 3D environments. The overall goals of this project are to understand how 3D structure affects EV production and to identify metabolic pathways controlling this response. To accomplish these goals, the project team will: 1) investigate the effects of 3D hydrogel microenvironments on EV function, 2) determine the effects of manufacturing strategies on EVs, and 3) define metabolic changes associated with EV production. It is anticipated that the mechanisms identified will have relevance for MSC-EVs for different therapeutic applications and for EVs generated by other cell types.

Funder: National Science Foundation

Amount: $547,347

PI: Ross Marklein, College of Engineering