Author: orandall

Single-cell analyses have uncovered diverse cell-type-specific features, yet how cis-regulatory elements (CREs) encode spatial expression patterns in plants remains poorly understood. To address this gap, we will establish a CRISPRbased perturbation platform in soybean hairy roots that uses base editors, error-prone polymerases, and helicases to generate dense local sequence variants, coupled with single-cell multiomic profiling. By delivering >1,000 gRNAs targeting ~300 proximal accessible chromatin regions across major root cell types, we will create large-scale variant–expression datasets that directly link CRE mutations to cell-type-resolved regulatory activity. We will then build a deep learning model that predicts CRE activity from DNA sequence and a generative model that designs synthetic CREs with desired spatial expression patterns. Using Bayesian experimental design, we will iteratively select and test informative edits through pooled editing and single-cell profiling, closing the loop between model design, perturbation, and measurement. This framework will enable scalable dissection of plant cis-regulatory grammar and provide a generalizable strategy for machine-guided, cell-type-specific engineering with broad applications in plant biology and crop improvement.

Funder: Simons Foundation 

Amount: $360,000 

PI: Hongwoo Lee, Franklin College of Arts and Sciences, Department of Genetics 

The entorhinal cortex (EC) is a critical mediator of cortico-hippocampal communication and thus essential for memory. Numerous studies identify the EC as the first brain region to display age-related changes such as accumulation of tau protein as related to Alzheimer’s disease (AD). Structural and functional changes to the EC have been found to precede and even predict future cognitive impairment. The EC is comprised of two subdivisions that are anatomically and functionally distinct, the lateral EC (LEC) and medial EC (MEC). Human studies have found that of these, the LEC is the earliest affected by age. I have previously found that loss of basal forebrain cholinergic input (BFCN) to the LEC is a critical component of LEC-related cognitive impairment and an early feature of the aging pathology. Cholinergic neurons are essential for normal attention, mood, and memory. Marked reductions of cholinergic neurons are a hallmark of AD. Despite the importance of each of these regions to pathological aging, the molecular determinants of the selective and early vulnerability in the BFCN to EC circuit is not known. The proposed studies will identify molecular signatures of vulnerability and the sequence of events that ultimately renders the BFCN to EC circuit particularly vulnerable to age. Using transcriptomics, high-resolution microscopy, and behavioral assays, I will identify the unique signatures of BFCN and LEC vulnerability in aging. Aim 1 studies will focus on the BFCN, classifying young and aged BFCNs based on their unique gene expression profiles, identifying LEC-projecting BFCNs, and evaluating the consequences of targeted LEC disruption on subsequent behavior, BFCN integrity and the BFCN transcriptome. In parallel, Aim 2 studies will focus on the LEC, classifying young and aged LEC neurons based on their gene expression profiles, evaluating the integrity of LEC neurons in aged animals, and evaluating the consequences of targeted BFCN disruption on subsequent behavior, LEC integrity and the LEC transcriptome. Taken together, the goal of this proposal is to identify the signatures of vulnerability in the circuit between the BFCN and LEC in aging and evaluate whether LEC dysfunction or BFCN deterioration drives circuit decline. In addition, the datasets generated from these studies will allow targeted assessments of the LEC or BFCN subpopulations in the future with the hopes of finding novel targets for ADRD treatments.

Funder: NIH 

Amount: $596,696 

PI: Mala Ananth, Franklin College of Arts and Sciences, Department of Cellular Biology 

Blueberry production in the US is threatened by spring freeze damage and summer heat stress. Addressing these issues aligns with the AFRI legislative priority to “Genetically dissect and introduce desirable traits to improve plant’s tolerance to temperature extremes associated with climate change”. Warm spring temperatures promote early blooms which elevates the risk of early freeze damage; delaying flowering time will reduce the risk. Conversely, when the blueberry fruiting season enters the sizzling summer days, fruit quality is compromised due to heat stress. Shortening the fruiting period will allow the fruits to mature sooner and minimize economic losses to heat stress. Our blueberry breeding population is suitable for genetic dissection of these two critical phenological traits because it exhibits wide ranges of variation in both blooming time and fruiting period. In addition, high correlations between two years of visual ratings indicate strong genetic inheritance of both traits. The objective for this proposal is to identify genetic regions and genetic markers controlling blueberry flowering time and fruiting period through a pangenome graph-based genotyping and phenomics approach. The long-term goal of this project is to develop climate-resilient blueberry cultivars and enable climate-smart farm management. An expanded pangenome graph, genetic markers and phenomics data complementary to the VacCAP project will be made publicly available. These advanced genotyping and phenotyping resources will accelerate trait pyramiding for the blueberry breeding community. Furthermore, a mobile phone App informing blueberry phenological development will be available to growers to enable data-driven farm management decisions.

Funder: USDA NIFA 

Amount: $617,000 

PI: Ye (Juliet) Chu, College of Agricultural and Environmental Sciences

This effort will produce accurate and contemporary population estimates for the South Georgia bear population (SGP). 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 and camera-trapping efforts. Analyses will be supplemented by GPS spatial data collected by Georgia Department of Natural Resources – Wildlife Resources Division (DNR). Collectively, these datasets will provide information on black bear survival, reproduction, and recruitment in the SGP.

Funder: U.S. Department of Interior 

Amount: $1,443,762 

PI: Michael Chamberlain, Warnell School of Forestry and Natural Resources 

This project will assist the Department of Community Health (DCH) in strengthening the disaster resilience of Georgia’s rural hospitals, skilled nursing facilities (SNFs), and inpatient hospice facilities through the Emergency Preparedness – Shelter in Place Initiative as part of the Georgia Rural Health Transformation (GREAT) Program. Our collaborative efforts aim to address one of DCH’s most consistent challenges: the high cost, risk, and logistical complexity of relocating vulnerable patients or residents during natural and human-made disasters. This initiative aims to improve patient and resident outcomes by ensuring that rural hospitals, SNFs, and inpatient hospice facilities remain long-term, resilient access points for care by improving their ability to operate during disasters. By supporting continuity of healthcare services and reducing dependence on high-cost and high-consequence evacuations, Georgia will achieve sustainable resilience that endures well beyond the five-year Rural Health Transformation Program funding cycle. The program objectives are (1) Comprehensive understanding of rural healthcare facility capabilities and needs through the compilation of existing data and in-person assessment of facilities; (2) Development of facility assessment tools, methodologies, and data management ecosystems; (3) Enhancement of rural healthcare service continuity by assisting facilities with grant writing and contractor identification.

Funder: Georgia Department of Community Health 

Amount: $3,735,000 

PI: Morgan Taylor, College of Public Health 

Healthcare worker (HCW) workload is a modifiable factor with strong relationships to both HCW well-being and patient safety. Team-based care is the gold standard for the treatment of critically ill patients in the intensive care unit (ICU). The robust body of evidence suggests that high workloads in the ICU are significant drivers of medication errors and HCW burn-out. While ICU physicians and nurses have developed workload standards in siloed efforts to create safe conditions, these analyses have omitted the interprofessional ICU team that includes critical care pharmacists, dietitians, respiratory therapists, advanced practice providers, and occupational/physical therapists. To date, no workload studies have evaluated the interdependent nature of the ICU team. Moreover, most workload metrics that hospital administrators use to make decisions do not reflect how work is actually conducted at the ICU bedside. We will build a workload visualization tool (Data-dRiven ICU Volume intErvention [DRIVE] dashboard) that will continuously analyze EHR data to provide multi-layered, time-tracking summaries that connect patient-level data to workload for the ICU team (Aim 1). The goal of DRIVE is to serve as a quantitative display of ICU team workload with metrics that directly reflect HCW and patient safety. In Aim 2, we will test a data-driven workload implementation framework (ICU Professional Resource Optimization [ICU-PRO]). In the ICU-PRO use case, we will assess the impact of a critical care pharmacist workload optimization intervention on medication errors and HCW safety. The rationale for this work is the results of the Optimizing Team Integration of Critical Care Pharmacists (OPTIM) study, which included >30,000 ICU patients from 64 centers that found that a high patient care workload for pharmacists was independently associated with increased mortality and length of stay, even after adjusting for relevant confounders such as disease severity and nurse ratio. Moreover, this study was the first to link a single healthcare profession workload (i.e., pharmacy) to patient outcomes in the context of the entire ICU team. The long-term goal is to improve safety and quality through optimization of ICU team workload. The central hypothesis is that optimized workloads are associated with improved HCW and patient safety. This innovative approach will explore previously undefined relationships for ICU workload and patient outcomes.

Funder: Society of Critical Care Medicine

Amount: $100,000

PI: Susan Smith, College of Pharmacy

The goal of this proposal is to invest in the capacity and infrastructure of the Southeast Coastal Ocean Observing Regional Association (SECOORA) glider observatory to develop, test, and implement autonomous passive acoustic monitoring of North Atlantic right whales in the South Atlantic Bight (SAB). Critically endangered North Atlantic right whales experience high mortality rates due to ship strikes and entanglement in fishing gear. These anthropogenic mortalities occur across the right whale habitat, including the northern foraging grounds, the Mid-Atlantic Bight migratory corridor, and the Southeast US calving ground off the coasts of South Carolina, Georgia, and Florida. A significant Unexpected Mortality Event beginning in 2017 has motivated the use of dynamic right whale management, a strategy that changes management based on near-real time visual and/or acoustic monitoring. Despite the expansion of passive acoustic monitoring efforts and studies on the efficacy of this approach in right whales’ northern foraging grounds, acoustic monitoring is much more limited in the Mid-Atlantic migration corridor and the Southeast US calving ground. Methods developed in the deeper waters of the foraging grounds may not be appropriate for use in the very shallow waters of the Southeast US calving ground. The proposed work would include the purchase of a passive acoustic monitoring science bay for use in a SECOORA glider, and four right whale monitoring missions on the Southeast US shelf during winter calving seasons. This project builds on recent test deployments of autonomous underwater vehicles called gliders, outfitted with an integrated passive acoustic recording system and onboard analysis that permits identification of the vocalizations of several baleen whale species, including the endangered North Atlantic right whale, in near-real time. These observations and experiments will support and expand existing networks for right whale monitoring led by collaborators at NOAA and Woods Hole Oceanographic Institution. UGA’s Sidaway Institute of Oceanography (SkIO) The team will purchase a Teledyne Webb Slocum glider science bay equipped with passive acoustic monitoring instrumentation that can be integrated into the SECOORA and/or SkIO gliders. The glider would be equipped to measure conductivity, temperature, and depth. UGA’s SkIO and the University of South Carolina will conduct glider missions to monitor North Atlantic right whiles in the SAB for a total of at least four missions during winter calving seasons over the three-year project. The UGA SkIO team will lead glider operations, with assistance in deployment, recovery, and auxiliary data collection from the University of South Carolina team. The PIs will expand the impact of this work through engagement with SECOORA stakeholders and partners, and through communication designed to reach scientific and non-scientific audiences.

Funder: NOAA (in partnership with SE Coastal Ocean Observing Regional Association, SECOORA)

Amount: $185,000

PI: Catherine Edwards, Franklin College of Arts and Sciences, Department of Marine Sciences

The Urban Agriculture and Life Sciences Summer Institute will build the capacity of urban educators to recruit and retain the next generation of urban agriculturalists by increasing engagement, knowledge acquisition, and knowledge retention of students using culturally responsive practices. For this project, 36 middle and high school educators will be selected to participate in a summer institute to learn how to develop and implement culturally responsive ALS lessons through professional learning, field experiences, and mentorship. Additionally, 18 previously trained educators will receive additional training on transformative mentoring and serve as instructional design support for teachers during curriculum development and implementation. The goal for implementing culturally responsive curriculum is to encourage student identity expression, increase problem-solving skills, and strengthen career aspirations related to ALS in urban settings. The expected outcomes for this four-year project are: 1) Expand the Urban Agriculture and Life Sciences Academy (UALSA) community of educators to include teacher mentors who support the creation and advancement of high quality and culturally responsive instruction; 2) Develop culturally responsive lessons focused on food safety, nutrition, and health in the areas of animal science, food science, horticulture, agricultural business and finance, environmental science and natural resources, and agricultural technology; and 3) Pilot culturally responsive ALS lessons, make revisions, and upload completed lessons to an online repository. All participants will receive membership to UALSA’s virtual community of practice, culturally responsive ALS curriculum, and other CRP resources and support to advance the implementation of the curriculum in classrooms.

Funder: USDA NIFA

Amount: $500,000

PI: James Anderson, College of Agricultural and Environmental Sciences

The purpose of this co-operative agreement is to develop a two-pronged immunoprophylactic strategy for the prevention and control of highly pathogenic avian influenza (HPAI) in poultry. We aim to develop a rapid and cost-effective immunotherapeutic designed to protect highly susceptible young chicks and to be deployed during emergency outbreaks. In parallel, we will also develop a vectored vaccine capable of inducing durable immune responses. By combining a rapid-acting immunotherapeutic with a robust vectored vaccine, this project aims to establish a comprehensive strategy for the prevention, control, and emergency preparedness of HPAI. Objective 1 will focus on developing an avian adeno-associated virus (AAAV) vector, termed AVI-Bloc, that encodes broadly neutralizing anti-influenza virus antibody in different formats (IgY, IgA and scFv). These constructs will be evaluated for efficacy in chickens using both individual and mass administration, including oral, aerosol and gel-spray delivery. We will generate a packaging cell line for low-cost production of AVI-Bloc vectors. Objective 2 will focus on establishing a DIVA-compatible vaccine platform using Rispens strain of Marek’s disease virus to deliver H5N1 hemagglutinin (HA) and neuraminidase (NA) antigens. We will develop immune-complexed, and M-cell targeting MDV vectored vaccines and evaluate their immunogenicity in birds. In objective 3, the protective efficacy of AVI-Bloc immunotherapy will be rigorously tested in challenge studies, particularly its ability to protect highly susceptible young chicks and provide rapid protection during emergency outbreaks. The protective efficacy of MDV Rispens-based immune-complexed and M-cell targeting vaccine candidates will be evaluated in HPAI challenge studies. We will measure neutralizing antibody responses, durability of protection, and the effects of immune-complexed antigen and M-cell targeting on the immunogenicity and protective efficacy of vaccine candidates. Key deliverables include the AAAV-based immunotherapeutic, low-cost scalable packaging cell line, a bivalent vaccine for HPAI and Marek’s disease, innovative tools for immune-complexed and M-cell targeting vaccine design along with the protocols for developing these immunoprophylaxis tools. The primary beneficiaries will be small and large-scale poultry producers, animal health biologics manufacturers, research scientists, poultry veterinarians, and policymakers. The outcomes are expected to provide rapidly deployable and effective immunoprophylactic tools for strengthening HPAI outbreak preparedness.

Funder: USDA APHIS

Amount: $1,999,861

PI: Lok Joshi, College of Veterinary Medicine

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Despite technological advancements, the 5-year survival rate for advanced HNSCC has remained stagnant for the past three decades. The FDA has approved immune checkpoint inhibitors (ICIs), including pembrolizumab and nivolumab, for the treatment of recurrent and metastatic HNSCC. While immunotherapy can induce durable remissions, only 15–20% of patients respond to treatment. There is growing interest in combining ICIs with chemotherapy or radiotherapy to enhance therapeutic efficacy. However, this approach has faced significant setbacks in recent clinical trials. Emerging studies suggest that the lack of activated dendritic cells (DCs) in tumors is a major reason for immunotherapy failure. Therefore, developing therapeutic strategies that not only eliminate cancer cells but also release stimulatory factors to promote intratumoral DC maturation and migration holds great promise for enhancing tumor sensitivity to immunotherapy. Our goal is to develop a novel adjuvant nanotechnology based on 7-dehydrocholesterol (7DHC)- encapsulated synthetic low-density lipoproteins (7DHC-LDLs) to boost anti-tumor immunity when used in combination with ICIs. 7DHC, a cholesterol analog, exhibits the highest rate of free radical chain propagation among known lipid molecules. Our preliminary data demonstrate that 7DHC-LDLs, like natural LDLs, accumulate in tumors by binding to the LDL receptor, which is upregulated in HNSCC. In the presence of reactive oxygen species (ROS), 7DHC triggers and amplifies lipid peroxidation in cell membranes, leading to ferroptotic cell death. In addition, our data suggest that cancer cells killed by 7DHC release danger-associated molecular patterns (DAMPs) and pro-inflammatory cytokines, which activate DCs and enhance tumor-reactive T cell priming, even in immunologically “cold” tumors. In this project, we will evaluate the pharmacokinetics and biodistribution of 7DHC-LDLs in orthotopic HNSCC models. We will test whether the innate adjuvant effects of 7DHC-LDLs can be leveraged to enhance the efficacy of anti-PD-L1 checkpoint blockade. Finally, we will perform a comprehensive analysis of the tumor microenvironment to elucidate the impact of this combination therapy.

Funder: NIH

Amount: $3,072,426

PI: Jin Xie, Franklin College of Arts and Sciences, Department of Chemistry