Category: 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

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

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

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

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

We propose to investigate whether water from the Okefenokee Swamp flows into the underlying Upper Floridan Aquifer—a key source of drinking water for communities in southern Georgia and northern Florida. While past studies hinted at a possible connection, no one has directly compared the swamp’s water with nearby groundwater using modern scientific tools. This project will collect water samples from the swamp, nearby rivers, and underground wells, and test them for natural “tracers” like stable isotopes, gases, and chemicals. These tracers help reveal where the water came from and how long it’s been underground. Early results suggest swamp water may already be entering the aquifer. Confirming this connection would help scientists, water managers, and other stakeholders better understand how the aquifer gets replenished and how to protect it. In addition to testing whether the swamp recharges the aquifer, we will also evaluate whether upward gradients exist—suggesting that groundwater may discharge into the swamp under certain conditions. Our findings will support improved conceptual and numerical models that can forecast hydrological responses to mining or other withdrawals.

Funder: Chemours Company

Amount: $259,242

PI: Jaivime Evaristo, Warnell School of Forestry & Natural Resources

This project addresses the Big Question: how can anthropologists and theologians responsibly navigate the extremes of relativism and unreflexive judgmentalism to support good human lives? While both disciplines have explored the concept of good human lives, a collaborative approach is urgently needed to tackle the analytical challenges posed by relativism, which can devolve into amoral nihilism, and judgmentalism, which risks becoming moralistic reproach. By combining theological insights with anthropological methodologies, this project seeks to establish a robust framework for assessing religious doctrines and practices in ways that meaningfully contribute to living good human lives. To this end, the project fosters active collaboration between theologians and anthropologists through a structured series of engagements, including monthly Zoom meetings, two in-person workshops and two master classes. These gatherings will bring together senior and emerging scholars from diverse backgrounds to engage in sustained dialogue and develop innovative approaches. A key objective is to explore definitional criteria for good human lives that remain attentive to cultural and theological particularities while resisting reductive universalism. Through these discussions, anthropologists will gain tools to critically navigate cultural relativism and judgmentalism, while theologians will be encouraged to bridge the gap between professed faith and lived experience, ensuring their contributions are both reflective and practical. By integrating theological and anthropological perspectives, the project aims to provide actionable insights that can positively influence good human living across diverse cultural and religious contexts. The project’s outputs will include an edited book, a special journal issue, podcasts, and conference presentations to share the resulting framework designed to inform both academic inquiry and practical applications.

Funder: Templeton Foundation

Amount: $259,255

PI: James Lemons, Franklin College of Arts & Sciences, Department of Religion

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Chemsex is a practice of drug use before or during sexual activity to facilitate, enhance, prolong, and sustain sexual pleasure. The drugs that are most commonly used in chemsex include crystalized methamphetamine (crystal meth), gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL), mephedrone, amyl nitrite, ketamine, and ecstasy/MDMA. They are chosen for their disinhibition effects on the common social, psychological, and physiological barriers to sex, like self-consciousness, concerns about partner’s HIV status, and pain experienced during sex. The relationship between chemsex and risky sexual behaviors has been identified in various studies with potential implications for increasing HIV and sexually transmitted infections (STIs). Chemsex is more prevalent among gay, bisexual, and other men who have sex with men (GBMSM), and it is associated with condomless sex, group sex, transactional sex, and negative health outcomes such as STIs and mental health issues. Despite the complex interplay between recreational drug use, high-risk sexual practices, and STIs among GBMSM, there is a lack of knowledge about chemsex practice patterns and harm reduction approaches, like HIV pre-exposure prophylaxis (PrEP) use among GBMSM in the South. This study will seek to identify psychosocial drivers and social contextual factors associated with chemsex among GBMSM that are amenable to intervention using ecological momentary assessment (EMA). An experienced and well-positioned research team will use a socioecological lens to examine individual factors, such as mental health issues (depression, anxiety, traumatic stress, lack of self-efficacy and resilience), substance use, HIV prevention knowledge and intentions (e.g., PrEP, condom use); interpersonal factors, such as social support, stigma and discrimination, peer substance use norms, gay community connectedness; and structural factors, such as availability and usage of preventive and curative services and support services. Understanding modifiable factors and knowledge of and intentions to use services are important steps in developing effective strategies for behavioral harm reduction interventions for chemsex. In this context, the current study intends to achieve (Aim 1) examine features of chemsex, e.g., types and dosage of drug use, frequency, number of partners, place, psychosocial drivers, and harm reduction approaches using in-depth interviews among 20 GBMSM; (Aim 2) Collect real-time data on drug use, sexual behavior, chemsex, psychosocial variables, and harm reduction approaches among 142 GBMSM who practice chemsex using EMA to (a) assess the usability of EMA for chemsex data collection; (b) examine the patterns of chemsex; and (c) identify the psychosocial drivers and modifiable factors associated with chemsex among 142 GBMSM who practice chemsex. This study will provide preliminary data on the patterns of chemsex, psychosocial, and other drivers of chemsex, PrEP, and condom use among the GBMSM in Georgia, a Southern state with high HIV burden. This study will also evaluate the effectiveness of the EMA approach for tracking chemsex practice among GBMSM.

Funder: NIH

Amount: $405,490

PI: Mohammad Rifat Haider, College of Public Health

Malaria is a serious disease caused by the parasite Plasmodium, which initially infects liver cells before spreading to red blood cells and causing a potentially lethal infection. Traditionally, this early liver stage was considered to be relatively invisible to the immune system. However, recent studies, including our own, have found that liver cells can detect and respond to Plasmodium using their natural immune defenses. When Plasmodium enters liver cells, the cells recognize the parasite’s presence and activate a chain of immune responses. These responses include producing reactive molecules, recruiting cellular machinery to attack the parasite’s protective bubble, and eventually breaking it down. As the parasite’s barrier is compromised, its DNA is exposed, triggering further immune actions that lead to the destruction of the infected liver cells. Together, these actions help control the parasite in the liver. However, Plasmodium can still survive in a small portion of liver cells, allowing it to continue its life cycle and eventually spread to the blood. This is enough to cause a potentially lethal malaria infection. We believe that Plasmodium uses special proteins we call ‘exported effectors’ to counteract the liver cell’s defenses, helping it evade destruction in these few cells. Our research aims to identify these protective proteins from Plasmodium and understand how they work. Our approach includes systematically identifying these parasite proteins, studying their behavior, and exploring how they interact with the mediators of liver cell defenses. By uncovering these survival tactics, we hope to find new ways to prevent the parasite from neutralizing our liver cells’ defenses, allowing the liver cells to clear the parasites more effectively.

Funder: Burroughs Wellcome Fund

Amount: $505,000

PI: Samarchith Kurup, Franklin College of Arts & Sciences, Department of Cellular Biology

This project will advance our understanding of soil processes that control the amount of carbon stored in soil. Understanding the controls on soil carbon storage and loss are critical for managing our natural environment for plant productivity, for improving our water quality, and for mitigating the effects of anthropogenic climate change. This project involves a series of experiments that will describe how fire and erosion impact the storage of carbon in soil, how it is chemically transformed over time, and how it may impact water quality. The results of this work will inform land managers in both urban and forested areas to make management decisions to improve productivity, increase carbon storage, and improve water quality. The educational component of this project will make collected data publicly available for educators in teaching modules that can be freely used to teach about soil, water quality, and the natural environment. The aim of this research project is to determine the relative importance of burn severity, soil type, erosion, and time since fire as drivers of dissolved organic matter (DOM) and pyrogenic carbon (PyC) quality and quantity in soils and outflow water. This work will be achieved by (1) collecting intact soil cores from plots with differing burn severities and conducting simulated leaching experiments to quantify throughflow of PyC and DOM, (2) establishing sediment fences to describe the role of burn severity on sediment and the related DOM quality from water extracted sediments to demonstrate the importance of sediment as a source of PyC into DOM, and (3) establish a tree vault study with applied PyC (as biochar) with two soil types (sandy and clay; typical of Georgia, USA) to describe the rate and quality of throughflow of applied PyC over longer time scales. Coupling these field and laboratory studies on different temporal and experimental scales will reveal the relative importance of different controls on the formation and transport of DOM and dissolved PyC, a significant and not well understood component of the global soil carbon cycle.

Funder: NSF

Amount: $836,711

PI: Rebecca Abney, Warnell School of Forestry & Natural Resources