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Notable Grants

Meiosis is a tightly controlled process during which the diploid genome must segregate into haploid gametes (e.g. eggs or sperm). Inheritance of the incorrect number of chromosomes is a leading cause of fertility and birth defects. However, the reasons for chromosome missegregation are not always the same for all chromosomes. Why inter-chromosomal differences exist is still unclear. One key contributor appears to be either a complete loss of crossing over or abnormal crossover placement. Drosophila melanogaster is a powerful model to better elucidate the regulation of chromosome-specific crossing over and the effects on chromosome segregation. In most cases, mutants that disrupt crossing over do so uniformly across the genome making it difficult to understand how chromosome-specific defects occur. However, a set of mutants in a partial loss-of-function synaptonemal complex mutant exhibit substantially different defects in pairing and recombination on the X chromosome and the autosomes. The synaptonemal complex is a conserved meiotic structure that holds homologous chromosomes together and is necessary for crossing over. The long-term goal of this project is to understand the chromosome-specific mechanisms that lead to error-free meiotic outcomes. This work will investigate 1) how chromosomes are identified as unique by the meiotic machinery and 2) how positioning of DSBs and crossovers is regulated on specific chromosomes. Overall, this project will provide insights into both the regulation of crossover location and meiotic chromosome biology. By studying the importance of individual chromosome behaviors and the synaptonemal complex in recombination, substantial advances can be made in understand the biology underlying the development of aneuploidies.

Funder: NIH

Amount: $1,625,336

PI: Katherine Billmyre, Franklin College of Arts and Sciences, Department of Genetics

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Notable Grants

This project, funded by the Bipartisan Infrastructure Law – Burned Area Recovery (BIL-BAR), will support the national native seed collection program, Seeds of Success (SOS), in its efforts to develop native plant materials for stabilizing, rehabilitating, and restoring post-wildfire lands. The award establishes the U.S. Forest Service’s (USFS) National Seed Laboratory (NSL) in Dry Branch, Georgia as a designated SOS cleaning and storing facility for the eastern United States to support native seed and plant material restoration nation-wide, a critical need for post-wildfire recovery and habitat restoration. Additionally, the project will provide the essential tools to ground-truth existing seed exchange zones, ensuring that plant species genetics are protected while maximizing economic viability for native seed use in post-fire restoration, including rebuilding native plant communities, stabilizing soil, and ensuring long-term ecosystem health on federal, state, local, and private lands. Large-scale disturbances, such as wildfires, threaten plant communities and damage ecosystems; yet ecologically appropriate native seeds are not readily available for restoration after catastrophic disturbances. Native plant species, particularly those adapted to local conditions, are more effective in facilitating rapid landscape-scale recovery from hazardous wildfire events compared to non-native species. The National Seed Strategy (NSS), developed in cooperation with conservation land management organizations, aims to address this demand for native seed by providing coordination and a framework for building an adequate supply of native seeds. The mission of the NSS is to ensure the availability of genetically appropriate seed to restore viable and productive plant communities through the SOS program. Specifically, the intent of the NSS is to achieve the right seed in the right place at the right time. The investigators will address three goals of the NSS: 1) Identify seed needs and ensure the reliable availability of genetically appropriate seed; 2) Identify research needs and conduct research to provide genetically appropriate seed and to improve technology for native seed production and ecosystem restoration; and 3) Develop tools that enable managers to make timely, informed seeding decisions for ecological restoration.

Funder: U.S. Department of Interior

Amount: $2,077,971

PI: Jennifer Cruse-Sanders, Franklin College of Arts and Sciences, Department of Plant Biology

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Notable Grants

African Americans in the rural South are often not included in studies focused on the developmental origins of cognitive decline and cardiometabolic disease, but they experience among the lowest life expectancies in the US among the lowest life expectancies in the US, a consequence of morbidity from chronic diseases of aging (CDAs) and Alzheimer’s disease and related dementias (ADRD). This omission is concerning because the pathways leading to chronic disease may be unique for African Americans. Emerging evidence suggests that both CDAs and ADRD are conditions that develop over the lifespan. Wear and tear from chronic stress, beginning in childhood and continuing throughout the life course, weathers multiple physiological systems, increasing disease vulnerability, including risk for cardiovascular disease, diabetes, and dementia. Since 2001, the Strong African American Families Healthy Adult Project (SHAPE) has followed a cohort of rural African American youth participating in an investigation of risk, resilience, and development. When participants were age 19, we expanded our investigations to address biological weathering. We found that exposure to family economic hardship and environmental stressors in late childhood and adolescence forecast biological weathering during emerging adulthood as evidenced by allostatic load, inflammatory activity, and epigenetic aging. For rural African Americans, the fourth decade of life has significant potential to affect biological weathering and CDA/ADRD vulnerabilities for better or worse. The influences of poverty, community disadvantage, and interpersonal stressors combine to render rural African Americans’ transitions to middle age especially challenging and stressful. Despite challenging conditions, many SHAPE participants will maintain in good health and some may improve their health. During the next 5 years, SHAPE participants will be exposed to continued and, in some cases, amplified contextual stress. Some participants will evince escalation in their weathering trajectories and the emergence of health problems, whereas others will not. The proposed research is designed to investigate the reasons why by collecting two waves of additional data when SHAPE participants are ages 35 and 37. Data collection will include biological markers of weathering, clinical indicators of cardiometabolic health, behavioral indicators of cognitive function, and reports of functional limitations. Participants will also provide information about psychosocial functioning and behavioral risk and protective factors. Our specific aims are to leverage this “deeply phenotyped” longitudinal study to: (a) test hypotheses regarding precursors of pre-disease warning signs, functional limitations, and cognitive decline; (b) evaluate the interconnectedness of physical health and cognitive decline by evaluating shared biological processes that might foreshadow risk; and (c) evaluate protective factors that prevent stress exposure from affecting rural African American adults’ health and cognition as they enter midlife.

Funder: NIH

Amount: $3,201,621

PI: Katherine Ehrlich, Franklin College of Arts and Sciences, Department of Psychology

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Notable Grants

The adrenal glands are vital endocrine organs, comprising the medulla and cortex, that control stress responses, metabolism, blood pressure, and immunity. We hypothesize that better understanding of medulla and cortex development, their interaction and pathologies will unlock novel treatment options for adrenal gland disorders. Our long-term goal is to use human pluripotent stem cell (hPSC)-derived 2D and 3D models to explore adrenal gland development, disorders, and therapies. Using hPSCs, we have made progress in generating adrenal gland cell types in 2D and 3D, laying the foundation for the proposed studies. Medullary chromaffin cells originate from neural crest (NC, ~20%) and Schwann cell progenitors (SCPs, ~80%), but the reason for this dual origin remains unknown. We will differentiate NC- and SCP-derived chromaffin cells in 2D and 3D and assess differences in their functions and physiological responsibilities. Adrenal gland insufficiencies are treated with hormone- replacement therapies targeting the cortex only. There is evidence that the influence of the medulla is substantial in homeostasis and disease, but it remains unknown if and which paracrine signals mediate this communication. We will use co-culture systems to identify molecules that mediate this interaction and will explore the role of defective communication in Congenital Adrenal Hyperplasia (CAH) 3D organoids. Current standard of care hormone-replacement therapy falls short of addressing daily, dynamic and demand-based patient’s needs. We generate 3D adrenal gland organoids for a cell replacement therapy approach for adrenal insufficiency. Our research efforts will advance our understanding of adrenal gland development, the significance of its multiple developmental origins, and medulla-cortex communication’s role in health. Additionally, we’ll gain insights into potential cell therapy approaches for adrenal gland diseases.

Funder: NIH

Amount: $3,310,746

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

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Notable Grants

The National STEM Teacher Corps Pilot Program: Georgia – Elevating Science Teachers’ Excellence Everyday Matters (GA-ESTEEM) project will address the critical need to elevate Georgia’s K-12 science teachers who have demonstrated excellence in teaching science and strengthen the work of new and existing science teachers. This five-year project will build alliances among professional organizations, state service agencies, and institutes of higher education to accomplish three goals: 1) identify and draw upon the expertise of 12 Georgia National STEM Teacher Corps (GA-NSTC) members; 2) empower current and emerging science teacher leaders; and 3) build and sustain science learning networks. To accomplish these goals, the project consists of an Executive Committee, an Advisory Committee, an external evaluator, and develops three Hubs. The Executive Committee consists of Hub leaders and Project Directors. The Advisory Committee consists of local and national experts to ensure the impact of the project. The evaluation team tracks the process and productivity of the project. Each Hub will consist of GA-NSTC members, individuals from Georgia’s science education associations and agencies, faculty and graduate students from institutes of higher education, and science teachers and teacher leaders. Each Hub will work in an area that strengthens Georgia’s K-12 science teacher workforce. The Hubs will work with one another, yet each Hub will have a unique role. Hub GA-NSTC will be responsible for identifying and supporting the work of 12 GA-NSTC teachers. These teachers will take on various roles in other Hubs and within their Georgia districts. Hub Capacity Building will be responsible for organizing established learning opportunities into new programming that targets newly hired science teachers, and builds the mentoring expertise of experienced science teachers. Hub Empower will curate advocacy and leadership programming for science teachers across Georgia. Each Hub will engage in synergistic alliance building and discovery with a focus on the success of all students.

Funder: NSF

Amount: $4,996,572

PI: Julie Luft, Mary Frances Early College of Education

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Notable Grants

Bacteriophages, or phages, are considered the most abundant organisms on Earth with an estimated 10+31 particles in the biosphere. These viruses are in a perpetual arms race with bacteria and arguably the major force driving bacterial evolution. Similarly, phages continue to develop novel mechanisms to infect their host and avoid detection, and carbohydrates are central to all these processes. As a microbial glycobiologist, my research originally focused on understanding the mechanisms behind bacterial glycoconjugate biosynthesis where we discovered that bacteria are capable of N-glycosylating proteins and campylobacters synthesize capsules rather than repetitive lipopolysaccharides. These studies evolved into better understanding the selective pressures that promote selection for glycoconjugate variants and discovering that a single strain of C. jejuni can express over 1000 different capsule structures and many of these variations can be observed when combining the strain with different phages. Our curiosity has now expanded toward understanding the importance of other glycostructures involved in phage-host interactions beyond C. jejuni and beyond surface polysaccharides. Using the knowledge we gained in studying microbial glycoconjugate synthesis and phage-host interactions over the last two decades, current studies will focus on exciting new discoveries describing other phage glycosylated macromolecules. 1) We are eager to explore the two mechanisms used by C. jejuni phages to replace canonical DNA bases with non-canonical bases with 100% efficiency. This will involve investigating the activity of a new deoxyribosyltranferase and how it couples to a transglycosyltransferase that efficiently removes nucleobases post-replicatively. CryoEM structures of this transglycosyltranferase in comparison with less efficient enzymes will not only help us to understand the transfer mechanism, but can also lead to the development of new biotechnological tools for nucleic acid biosynthesis and vaccine development. 2) Recently a set of glycosyltransferases (GTs) responsible for glycan addition to capsids and tail tubes of phages infecting Mycobacterium species were identified, but these modifications showed no benefit to phage infectivity. We hypothesize that these GTs could also modify host proteins, including phage receptors that subsequently prevent phage superinfection. We propose to use our methods in recombinant bacterial glycoengineering as well as GT expression in the native host to better understand the impact of phage GT expression on the microbe as well as expand the toolbox of novel characterized enzymes available for therapeutic development. 3) All cystoviruses isolated to date infect Pseudomonas species, but we recently isolated an enveloped virus infecting a multidrug resistant strain of Acinetobacter radioresistens. These viruses enclose themselves with bacterial inner membranes that also contain glycoconjugate biosynthetic machinery. We aim to verify their composition and better understand their biogenesis for possible use as maleable self-assembling nanoparticles.

Funder: NIH

Amount: $377,500

PI: Christine Szymanski, Franklin College of Arts and Sciences, Department of Microbiology

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Notable Grants

Coastal marsh environments exist at the intersection of human populations and the ocean. They provide economic output through commercial fisheries, tourism, and recreation and protect coastal communities during storm events. Coastal land managers and other stakeholders need vetted scientific information and user-driven tools to understand salt marshes’ vulnerability and to make informed decisions on management and policy actions to increase resiliency and protect vital habitats. This includes information regarding marsh extents, migration potential, and marsh productivity to understand impacts on critical species, designate future land use, and develop restoration strategies to mitigate marsh loss (e.g., thin layer placement, freshwater/sediment diversions). In making decisions regarding marshes, managers often rely on predictive models to assess vulnerabilities to changing conditions (e.g., climate, rising sea level) with associated uncertainty in model projections. Several marsh models are widely used to predict future marsh evolution, including (but not limited to) the Hydrodynamic-Marsh Equilibrium Model (HydroMEM), the Wetland Accretion Rate Model for Ecosystem Resistance (WARMER), Sea-Level Affecting Marshes Model (SLAMM), and NOAA’s Wetland Impacts and Migration Model (SLRWIMM). End users have expressed concerns and asked questions regarding the optimal selection of a marsh model tailored to a specific region, the interpretation of results, and the effective integration of these findings into their decision-making framework. Therefore, there is a need to evaluate the accuracy of existing marsh models and their utility to wetland managers and users through a coordinated approach that will enable more robust and reliable predictions.

Funder: U.S. Department of Commerce

Amount: $1,125,698

PI: Matthew Bilskie, College of Engineering

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Notable Grants

Transporters from the multidrug exporter/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily and the major facilitator superfamily (MFS) are central to multiple cell wall biopolymer biosynthesis pathways. Transporters from both superfamilies exhibit significant differences in their architecture, lipid substrate selectivity, and transport mechanisms. There are several critical gaps in our current understanding of the molecular mechanism of substrate recognition and transport, substrate specificity, ion-coupling, and activity modulation of lipid transporters from these two superfamilies. This project seeks to investigate the structure and function of two lipid transporters involved in teichoic acid synthesis: the glycolipid transporter LtaA from the MFS superfamily and the teichoic acid transporter TacF from the MOP superfamily. Thus far, my work has revealed the structure of LtaA in an outward-facing apo state. Additionally, computational methods, cysteine disulfide trapping, and AlphaFold modelling have been employed to validate inward-facing models of LtaA. Our findings revealed that in both outward- and inward-facing conformations, this protein displays an amphipathic central cavity crucial for diglucosyl-diacylglycerol transport, and suggest that LtaA employs a ‘trap-and-flip’ mechanism to facilitate glycolipid translocation. In contrast, there is currently a lack of structural and functional data regarding the mechanism of the MOP teichoic acid transporter TacF, and there are still many questions unanswered about the molecular mechanism of lipid transporters from both superfamilies. We have additionally explored the ioncoupled lipid transport mechanism of LtaA, recognizing its essential role in modulating the cell wall composition under acidic conditions. We hypothesize that ion-coupled co-transport of lipids may be linked to adapting the cell wall composition. However, there are few detailed studies on the precise mechanism of ion-coupling for MFS and MOP lipid transporters. In this application we want to reveal how LtaA and TacF select for their lipid substrate at the atomic level, elucidate their ion coupling mechanisms, and reveal the impact of membrane lipids on transport. Collectively, our proposed research will broadly impact the field of lipid transport by characterizing the molecular mechanism of transporters from two superfamilies commonly associated to cell wall biopolymer biosynthesis pathways. These studies have the potential to uncover novel molecular mechanisms underlying lipid and ion co-transport, which will be critical for understanding the function of cell wall lipid transporters in bacteria, and will potentially accelerate the structure-based drug design of activity modulators targeting these proteins.

Funder: NIH

Amount: $1,842,316

PI: Camilo Perez, Franklin College of Arts and Sciences, Department of Biochemistry and Molecular Biology

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Notable Grants

Regulatory T cells or ‘Tregs’ play a critical role in our health and well-being by suppressing over- exuberant immune responses. Antigen-specific Tregs, like other T cell subsets, are maintained for prolonged periods in the host as memory Tregs (mTregs). These are possibly recalled to protect against the immunopathology associated with repeated encounters with the same antigen. Initial observations supporting this notion in viral infection models have generated immense interest, especially from the fields of autoimmune diseases, allergy medicine, maternal-fetal medicine, or recurrent infectious diseases, where repeated exposures to self or non-self antigens are fundamental. Malaria, caused by Plasmodium, is one such disease, where humans residing in endemic areas get repeatedly infected. However, Tregs are known to impede the protective immune responses against Plasmodium during a primary infection. Therefore, we expected the mTregs also to behave similarly by hindering protection in both humans and mice following Plasmodium re-exposure. Surprisingly, humans possessing higher frequencies of mTregs exhibited reduced parasite loads upon reinfection. In mice also, the presence of mTregs promoted better control of repeat infections with Plasmodium. These findings suggested that Tregs behave differently in primary and secondary infections during malaria and challenged the fundamental concept of functional memory in T cells. The primary objective of this research proposal is to determine the mechanisms underlying mTregs-mediated protection and function in recurrent malaria. Our preliminary experiments suggest that the mTregs generated by Plasmodium infection transition to Tfh-like cells that promote anti-Plasmodium immunity. Our central hypothesis is that mTregs undergo inflammation-induced epigenetic modifications to enable their pheno-conversion into Tfh-like cells during recall and promote the generation of robust germinal center (GC) reaction and antibody responses. This would facilitate better control of Plasmodium reinfection. We will test this hypothesis by determining the molecular mechanism of the transition of mTregs to Tfh-like cells (Specific Aim1) and resolving how such a transition would promote immunity to Plasmodium reinfection (Specific Aim 2). We think that the mTregs maintained in malaria-experienced individuals are a transitionary state of Tfh cells, allowing such cells to survive for prolonged periods in the host. The completion of our proposed studies would provide new insights into how mTregs can impact disease outcomes in recurrent infections such as malaria, where reinfections constitute the majority of the clinical cases in humans.

Funder: NIH

Amount: $3,250,100

PI: Samarchith Kurup, Center for Tropical and Emerging Global Diseases

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Notable Grants

The Georgia Coastal Ecosystems (GCE) Long Term Ecological Research (LTER) program, which was established in 2000 to understand estuaries (places where salt water from the ocean mixes with fresh water from the land) and their adjacent coastal wetlands (i.e., marshes and tidal forests) and how they respond to long-term change. The GCE LTER researchers evaluate how environmental conditions (e.g., sea level, temperature, storms and hurricanes) and human activities (e.g., land use) affect the properties of estuaries (e.g., salinity, flooding patterns), and how that in turn affects wetlands and their ability to provide food and refuge for fish, shellfish and birds, to protect the shoreline from storms, to help to keep the water clean, and to store carbon, all of which have significant implications for the US economy. Many of the changes that are occurring are affecting not just average conditions, but also their fluctuations and extremes (e.g., variability). For example, not only has the average high tide level increased over the past decade, but the number of extreme flooding events has also increased, both of which have the potential to lead to wetland loss through drowning. During this award, the research team will conduct studies to systematically evaluate 1) whether we can improve our predictions of ecological responses by considering variability in environmental conditions, and 2) the use of variability as an early indicator of underlying environmental stress. The findings from this research will be important for predicting the long-term survival of coastal wetlands in a time of global change. In addition to research, the GCE program works with teachers and students, coastal managers, citizen scientists, and the general public to enhance scientific literacy and improve our understanding of coastal ecosystems. The GCE LTER is based at the University of Georgia Marine Institute on Sapelo Island, Georgia, and has a robust program of long-term field observations, experiments, remote sensing, and modeling designed to understand wetland ecosystem functioning. GCE LTER researchers will build on this foundation with an overlay of new efforts focused on variability. Objective (Obj) 1 is to characterize spatial and temporal patterns in mean and variability of drivers and responses by measuring external drivers (e.g., sea level), marsh and estuarine conditions, and the wetland biophysical template, and to integrate these dynamics via modeling. Obj 2 is to evaluate linkages between external drivers and ecological responses, and determine whether assessing the variability of abiotic drivers improves predictions of those responses. This will be done by analyzing long-term data, conducting field campaigns in areas with different variability in salinity and inundation, and conducting complementary mechanistic experiments to quantify the effects of driver variability (e.g., salinity). Obj. 3 is to assess disturbances and their effects on patterns of variability in ecological responses by tracking the effects of natural disturbances in the field along with ongoing experimental manipulations. Obj. 4 is to evaluate how ecological properties change across abiotic gradients, and determine whether variability increases near habitat transitions. This will be done using remote sensing, sampling across gradients of salinity and inundation, and establishing long-term monitoring sites in forested areas to track upland marsh migration. Obj. 5 is to determine the mechanisms by which coastal wetlands respond to changing drivers and assess whether variability informs this understanding. This will be done in three ways: by conducting statistical analyses relating key ecosystem variables (e.g., net ecosystem exchange, plant biomass) to drivers (salinity, inundation, temperature); by using remote sensing to investigate spatial and temporal patterns in the mean and variability of marsh productivity and their relationship to variability in climate drivers; and by synthesizing results to describe net daytime production and C stocks and predict how they might change in response to future conditions. The GCE education and outreach program will provide K-12 teachers with research experience that can be shared in the classroom, along with school visits. It will offer research opportunities through undergraduate internships, and run web-based courses for graduate students. The program will initiate a citizen science effort to delineate high tide flooding events, and will partner with the Georgia Coastal Research Council to exchange information with coastal managers.

Funder: NSF

Amount: $7,542,000

PI: Merryl Alber, Franklin College of Arts and Sciences, Department of Marine Sciences