Category: Notable Grants

Among the numerous problems plaguing the malaria elimination efforts is the emergence and spread of drug resistance in P. falciparum. Resistance to artemisinin has led to reduced efficacy of artemisinin combination therapy (ACTs) and ultimately selection of resistance to the partner drugs (e.g., piperaquine). Clearly, the threat of multi-drug resistant malaria is as important today as it has ever been, with the precious gains in malaria control threatened by the potential for the spread of P. falciparum strains that are resistant to all currently available treatment drugs. Resistance to artemisinin is not the only factor responsible for treatment failures. Even before artemisinin resistance emerged, recrudescent infections were commonly observed when patients were treated with artemisinin derivatives alone. In some studies, even 5-7 days of treatment with artesunate alone led to ~10% recrudescent infections. The underlying cause of these recrudescent infections has been attributed to the unique ability of artemisinin to arrest the growth of ring stages of P. falciparum. These dormant rings can persist for days to weeks before recovering and growing normally to cause a recrudescent infection. Our published and preliminary data led us to the hypothesis that selection of artemisinin resistance is a two-step process in which the initial responses of the parasite to artemisinin drug pressure is an enhanced dormancy phenotype that confers increased tolerance to drug; subsequently, resistance conferring mutations occur (e.g., K13). In Aim 1 we will overexpress genes in a novel chromosome 10 copy number variant we identified in independently derived artemisinin-resistant clones. In Aim 2 will use novel high content imaging assays to quantify enhanced dormancy recovery phenotypes in artemisinin-resistant versus -susceptible P. falciparum. The results of these studies will provide evidence for the molecular basis of recovery from artemisinin-induced dormancy and possibly reveal new mechanisms of resistance to artemisinin.

Funder: National Institutes of Health 

Amount: $415,250 

PI: Dennis Kyle, Franklin College of Arts and Sciences, Department of Cellular Biology 

Gulf coast resource managers and decision-makers are increasingly exploring how to improve community resilience in the face of extreme storms and sea level rise (SLR), particularly with nature-based infrastructure. The Coastal Dynamics of SLR (CDSLR) paradigm, a mature ESLR-funded approach developed in 2010, will be used to evaluate flood hazard mitigation and the socioeconomic and ecological benefits of flood mitigation projects for present and future climate change conditions. With direct support from a Management Transition Advisory Group, existing integrative numerical models will be combined with traditional and contemporary approaches in natural resource economics to evaluate mitigation project outcomes regarding efficiency, equity, environmental sustainability, and socio-economic resiliency. Outputs of this approach will include changes to flood hazards for migration projects and the socioeconomic and ecological impacts (monetary and non-monetary). The outputs will be tailored based on community needs and the requirements of the targeted funding agency (e.g., FEMA, NFWF, etc.).

Funder: U.S. Department of Commerce 

Amount: $427,655 

PI: Matthew Bilskie, Institute for Resilient Infrastructure Systems 

Georgia Department of Natural Resources (GADNR) Urban Wildlife Program responds to numerous calls from metro Atlanta residents about white-tailed deer becoming entangled in residential fences (e.g., wrought iron). These emergencies present concerns for the welfare of deer and the safety of residents and responding personnel. Although fences greater than 10 feet in height are known to prevent deer crossings, little research has been done to examine deer interactions with common fence designs in suburban areas. Understanding where deer-fence conflicts occur in metro Atlanta and the design features of fences which are problematic would offer opportunities to engineer improved fences and to modify existing fences to reduce deer entanglements. This study will utilize information from previous deer-fence conflicts and new data about the jumping behavior of captive deer to guide fence modifications. Additional testing with captive deer jumping modified fencing will be conducted. Finally, residents will be surveyed to determine preferences for fence modifications designed to reduce conflicts with deer relative to aesthetics, costs, practicality, and likelihood of reducing conflicts with deer. Ultimately, GADNR will be equipped with information to provide residents, municipalities, and homeowners associations wishing to reduce issues related to deer interacting with residential fences.

Funder: Georgia Department of Natural Resources 

Amount: $627,929 

PI: Gino D’Angelo, Warnell School of Forestry and Natural Resources 

The goal of this project is to develop a field deployable hydrogen sensor with environmental monitoring capabilities to detect hydrogen content at environmentally relevant conditions that meet DOE goals. The project is organized around three technical areas: research and development with laboratory testing, sensor system integration, and simulated field testing. The team of scientists and engineers includes university, national laboratory, non-profit, and industrial partners. The objective of this proposal is to harness fundamental principles to build and certify transformational electrical hydrogen sensors that can meet or exceed DOE goals by employing novel hydrogen-absorbing alloys, targeted optimization of nanostructure designs that leverage innovative nano-fabrication techniques, highly selective functionalized polymeric membranes, advanced electronic integration, and rigorous real-world testing. This DOE funding award will be a continuation and expansion of the research activity originally supported by the Laboratory Directed Research and Development program of the Savannah River National Laboratory. The challenges that are unique to environmental monitoring are the need for low-level detection, short response time, and stability in a single sensor. We will advance our sensors to meet the goals for environmental monitoring in a lightweight, robust, and economical sensor.

Funder: U.S. Department of Energy 

Amount: $999,611 

PI: Tho Nguyen, Franklin College of Arts and Sciences, Department of Physics and Astronomy 

The long-term goal of this project is to strengthen the use of partner-centered evidence to promote equitable design, implementation, and evaluation of human rights policies and practices; in turn, reducing the disparities between disenfranchised communities’ and funders’ knowledge and values. This project is innovative in that it attempts to actionably move evaluation to a community-collaborative and transformative approach that can promote shared stewardship over the realization of human rights objectives. The end result: Actionable evaluation frameworks and guides that exemplify the intrinsic values behind democracy, human rights, and governance policies and programming.

We have organized this proposal along the following objectives: Objective 1: Determine specific priority regions and questions to be addressed through desk review and community mobilization; Objective 2: Assemble an advisory board and community researchers to guide the development of region- and thematic-specific sampling and data collection procedures; Objective 3: Gather and analyze policy and programmatic data to explore implicit and explicit theories of change and determine effective and equitable strategies; Objective 4: Conduct an in-depth test of human rights strategies in 4-5 regions using draft evaluation criteria / framework; Objective 5: To produce, test, and refine rigorous and relevant evaluation frameworks and guides for the DRG community. Through a cyclical process, learning from Phase 1: Global Equality Fund (GEF) will inform the design of subsequent phases, allowing us to refine evaluation frameworks and guides.

Funder: U.S. Department of State 

Amount: $1,771,623 

PI: Giovanni Dazzo, Mary Frances Early College of Education 

Cerebral atrophy is commonly encountered in penetrating severe Traumatic Brain Injury (sTBI) survivors. Brain infiltration of blood-borne cytotoxic proteins and immune cells due to cerebrovascular dysfunction is an important factor contributing to progressive cerebral atrophy and onset of Alzheimer’s Disease dementia in sTBI patients. However, there have been no efforts to develop interventional therapies that can prevent cerebrovascular dysfunction and infiltration of peripheral immune cells into the brain in penetrating sTBI. Our central hypothesis is that acutely implanted engineered Chondroitin Sulfate (eCS) 3D matrices will accelerate cerebrovascular repair and prevent cerebral atrophy and loss of function in sTBI rats. We propose to test our hypothesis using a novel preclinical rat model of penetrating sTBI in the following two specific aims: Aim-1. Characterize cerebrovascular permeability and immune cell composition in sTBI. Aim-2. Determine the effectiveness of eCS matrix implants in mediating cerebrovascular repair and functional recovery. The proposed studies are expected to provide novel insight into the role of cerebrovascular dysfunction in progressive neurodegeneration and cerebral atrophy in sTBI. Collectively, these studies will inform the development of tissue engineered brain implants that can accelerate cerebrovascular repair and prevent brain volume loss and functional deficits in sTBI patients.

Funder: NIH

Amount: $379,171

PI: Lohitash Karumbaia, College of Agricultural and Environmental Sciences, Department of Animal and Dairy Science

This project will make significant contributions to racial equity in STEM by identifying and describing forms of systemic racism inherent in mathematics teacher education programs (MTEPs). Racialized mathematics teaching practices are systemic in elementary mathematics classrooms, and the impacts of systemic inequities in K-12 mathematics education both deter students from diverse backgrounds from becoming interested in math, reducing their likelihood of engaging in STEM; and affect students? identities by devaluing or erasing their diverse cultural backgrounds and perspectives. Since teachers are the key to ensuring racial equity in classrooms, identifying racialized mathematics experiences must begin with mathematics teacher education programs. In this innovative study, a project team comprised of mathematics teacher educators of color (MTECs) will collaborate with 12-15 Preservice Teachers of Color (PTOCs), in authentic partnership, from three unique MTEPs (at an HBCU, an HSI, and a PWI) to form a cross-site Critical Mathematics Professional Learning Community (CMPLC). By documenting PTOCs? racialized mathematics experiences across three sites, the project will: (1) gather fundamental knowledge on the racialized mathematical learning and teaching experiences of PTOCs, (2) build knowledge of racialized mathematics experiences and their overall impact on the preparation of PTOCs, and (3) inform teacher education programs across content and contexts. As Black and Latinx scholars with extensive experience in teacher education, the project team conceptualized this creative project to illuminate new ways of nourishing and affirming PTOCs? racial identities and cultural strengths in mathematics teacher education.

The project team will collaborate with participating PTOCs to analyze data generated from focus groups, individual interviews, CMPLC conversations, journals, and field notes using interpretative phenomenology analysis, case study methodology, and thematic analysis. Participating PTOCs? students, especially the culturally and linguistically diverse students in their classrooms, will benefit from this project by receiving increased opportunities to learn mathematics in ways that bolster their STEM identities. The project will fill a gap in the research literature by: (1) increasing the knowledge on the mathematics teacher preparation of PTOCs; (2) centering the voices and experiences of PTOCs and mathematics teacher educators of color in a cross-racial and cross-cultural project; and (3) bringing unique perspectives to the design, implementation, evaluation, and dissemination of findings about both our own experiences and those of PTOCs, as a PI team composed entirely of MTECs. By attaining a deeper understanding of PTOCs? mathematics learning experiences, we advance racial equity by exposing racist teaching practices that disadvantage historically marginalized students and identifying changes in teacher education that will identify and address practices that obstruct racial equity in STEM.

Funder: NSF

Amount: $644,642PI: Dorothy White, Mary Frances Early College of Education, Department of Mathematics, Science, and Social Studies Education

Summary Parkinson’s disease (PD) is the second most common neurodegenerative disease. Loss of substantia nigra compacta (SNc) dopaminergic projections and decreased striatal dopamine levels are the characteristic features of PD. Emerging evidence suggest that synaptic dysfunction of dopamine neurons is an early event in the pathogenesis of PD occurring prior to the onset of symptoms. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent causes of familial and sporadic PD, demonstrating an unprecedented significant role in PD pathogenesis. A transgenic mouse model with over-expression of human LRRK2- R1441G has been shown to recapitulate robust motor behavioral, neurochemical and pathological features of PD. At the level of pathology, the most robust phenotype is the axonopathy of the nigrostriatal dopaminergic projection, accompanied by age-dependent hyperphosphorylated tau and DA transmission deficits. Both genetic and environmental causes of PD have highlighted the importance of mitochondrial dysfunction in the pathogenesis of PD. Mitochondrial trafficking is critical for neurons’ survival and functions including synaptic neurotransmission. However, mitochondrial trafficking and dynamics in mutant LRRK2 associated-PD has not been well studied. We find that the mitochondrial oxidant stress is elevated in the LRRK2-R1441G mutants whereas mitochondrial respiration and mitochondrial ATP synthesis is significantly reduced. In addition, our preliminary studies uncovered early and defining features in mitochondria trafficking and dynamics impairment: frangmented mitochondria in SNc dopamine neurons and terminals, increased cytosolic calcum levels, tau hyperphosphorylation, and decreased anterograde healthy mitochondrial transport. We hypothesize that R1441G mutation impairs mitochondria trafficking and dynamics via dysregulation of Miro1 and calcium homeostasis and pathologic tau accumulation that ultimately result in synaptic dysfunction, energy failure and axonal degeneration. We will utilize a combination of two-photon imaging (2PLSM) and electrophysiology recording in living brain slices, and mouse genetics to uncover mechanisms underlying DAergic transmission deficits and axonal degeneration in PD.

Funder: NIH

Amount: $1,711,466

PI: Hui Zhang, College of Veterinary Medicine, Department of Physiology and Pharmacology

Project Summary To survive in diverse environments, bacteria must dynamically interact with their physical surroundings to sense and incorporate stimuli into physiological responses. Bacteria often achieve this interplay between extracellular cues and intracellular signaling by using surface-exposed nanomachines that connect the intracellular space to the cell surface. The most broadly distributed surface-exposed nanomachines are appendages called type IV pili (T4P) and evolutionarily related structures that are believed to have diverged from an ancient nanomachine found in the last universal common ancestor. T4P are highly dynamic, employing multiple molecular motors to power cycles of extension and retraction that are essential for many behaviors, making them an ideal system for understanding the dynamic exchange between cells and their physical environments. Despite their broad distribution and importance in many biological processes, little is known about the fundamental biology behind T4P dynamics, regulation, and structure. We will use a combination of genetics, cell biology, biophysics, and biochemical techniques to dissect the fundamental biology of T4P. We will employ multiple model organisms including Caulobacter crescentus, Vibrio cholerae, and Acinetobacter species that all produce T4P for a comparative biology approach across different T4P. Our prior experience and expertise working in these systems will enable us to interrogate how T4P regulatory mechanisms evolve to respond to environmental stimuli and how these regulatory differences influence behavioral outputs. Our five-year goals include understanding the basic mechanisms driving T4P dynamics, how dynamics are regulated, and the consequences of different regulatory mechanisms on bacterial behavior and physiology. This work will address several key questions, including: 1) what are the main factors influencing dynamics? 2) what mechanisms control subcellular localization and patterning? And 3) how do structural subunits of T4P determine their functional and mechanical properties to influence diverse behavioral outputs? This work will provide critical insight into T4P regulation and dynamics that will result in better understanding of the physical interactions between cells and their environments and enable the development of tools to hinder or control T4P function in the broad bacterial behaviors they elicit. The fundamental discoveries made through our study of T4P will also reveal general aspects of biology including insight into the underlying mechanics of molecular motors, the mechanisms controlling intracellular spatial organization, and the relationship between protein structure and function.

Funder: NIH

Amount: $1,842,220

PI: Courtney Ellison, Franklin College of Arts and Sciences, Department of Microbiology

Project Summary/Abstract Smokers partnered with other smokers (i.e., dual-smoker couples) represent ~2/3 of all smokers. Dual- smoker couples (DSCs) are less likely to try to quit smoking and more likely to relapse during a quit attempt, reducing overall smoking cessation rates and representing a high-risk clinical population. Despite their high prevalence and risk for persistent smoking, however, there are limited data on smoking cessation interventions among DSCs. Building on previous research that suggests a) financial incentive treatments (FITs) are effective at increasing quit rates; and b) dyadic adaptations of FITs are feasible for implementation in DSCs, the proposed randomized controlled trial (RCT) will systematically examine two adaptations of FITs to enhance smoking cessation among DSCs. In addition to determining the efficacy of these FITs for smoking abstinence in DSCs, we will examine mechanisms of change, secondary endpoints and outcomes, and the cost effectiveness of each adaptation. We will address these questions in a three-group RCT that is informed by a highly supportive pilot trial we have completed on FITs for DSCs (R21CA241570). In all conditions, treatment-seeking smokers who are part of a DSC (i.e., targets) will receive usual care (combination fast and slow acting Nicotine Replacement Therapy + quitting resources). In two experimental conditions (single FIT and dyadic FIT, SFT and DFIT), participants will receive incentives for abstinence at three time points (1-, 3-, and 6-months post-baseline). In the SFIT condition, only the target in a couple will be offered incentives; in the DFIT condition, both target and partner in a couple will be offered incentives. Primary efficacy outcome is biochemically-verified abstinence at 6-months post-baseline among targets. We will concurrently evaluate candidate mechanisms of change (e.g., partner support, individual and partner motivation) to understand how FITs confer benefits and inform optimization. Secondary outcomes are point-prevalence abstinence at 1- and 3-months during the treatment and 6-months post-treatment (12-months post-baseline), as well as partner smoking outcomes. As FITs inherently rely on financial resources, cost-effectiveness analysis will quantify the cost and relative cost of positive outcomes within and across conditions. These data on the efficacy, mechanisms, and costs of FITs for DSCs will inform population level implementation and promote successful quitting in this treatment refractory population.

Funder: NIH

Amount: $2,920,773

PI: Michelle vanDellen, Franklin College of Arts and Sciences, Department of Psychology