PI – Jose M Alonso (Plant and Microbial Biology, CALS)

Co-Is – Anna N. Stepanova (Plant and Microbial Biology Department, CALS), Joseph Gage (Crop and Soil Science Department, CALS)

Abstract: Changes in gene expression are at the core of many biological processes, from forming a multicellular organism from a fertilized egg to surviving pathogen attacks or coping with environmental pressures. Although transcription regulation plays a critical role in modulating gene expression, growing lines of evidence indicate that gene-specific regulation at the translational level is also critical for many biological processes. Unfortunately, the existing technologies to quantify changes in translation, both at the genome-wide and single-gene levels, are technically demanding and costly, thus hindering the widespread investigation of this type of regulation. We have developed RiboPi (Ribosome Position Inference), a new method to quantify translation efficiency (rates of protein synthesis per transcript) that is technically simple, cost-effective, and has the potential to provide superior performance and richer information than current methods. With the support of this award, we will benchmark this new technology against the current gold standard and develop computational methods to extract and interpret translation-related information from the obtained raw data.

PI –Nick Buchler (Molecular Biomedical Sciences, CVM)

Co-I –Claire Gordy (Biological Sciences, COS)

Project Summary: The long-term goals of this project are to combine evolutionary cell cycle research with high-impact undergraduate education by developing a Course-Based Undergraduate Research Experience (CURE) in Genetics. The future CURE (“Genetics of the Cell Cycle”) will be implemented in the existing large-enrollment GN 312 course at NC State. Students will perform classic genetic mutagenesis screens, akin to the Nobel Prize-winning work of Hartwell and Nurse, to isolate, characterize, and clone cell division cycle (cdc) mutants. This work will be performed in novel, non-conventional yeast
species, beginning with Kluyveromyces lactis and later transitioning to Yarrowia lipolytica. These yeasts represent significant evolutionary divergence from the model S. cerevisiae and S. pombe, providing an opportunity to discover novel cell cycle regulators, and further our understanding of conservation and plasticity in cell cycle network evolution.
This project specifically requests funding to generate preliminary data (Spring/Summer 2026) to demonstrate the technical feasibility of the cdc mutant screen in K. lactis and to integrate such research into a CURE curriculum. Results will include developing CRISPR-based markers, high-throughput microscopy workflows, and genomic libraries. Preliminary data from this seed funding will directly support subsequent multi- investigator grant applications to the NSF IUSE and Spencer Foundation to support Discipline-Based Education Research, and NSF grants with NC State yeast geneticists interested in using K. lactis as a comparative model organism.

PI – Kurt Marsden (Biological Sciences, COS);

Co-Is – Seth Kullman (Biological Sciences, COS), David Muddiman (Chemistry, COS)

Abstract:A critical function of the nervous system is to rapidly process sensory information and initiate appropriate behavioral responses. Defects in sensory processing and behavior selection are commonly observed in neuro-psychiatric conditions including anxiety, autism (ASD), and schizophrenia (SZ). Despite the biological and clinical relevance, our understanding of the cellular and molecular mechanisms regulating these processes is limited, although intrinsic/genetic, extrinsic/environmental, and the interactions of intrinsic and extrinsic factors likely play fundamental roles.  Emerging evidence demonstrates the importance of sufficient vitamin D (1α,-25-dihydroxyvitamin-D3) during early development, as deficiencies are associated with global long-term adverse health effects into adulthood. While vitamin D is traditionally associated with mineral ion homeostasis, accumulating evidence suggests non-calcemic roles for vitamin D including neurodevelopment. However, large gaps remain in linking developmental vitamin D, sensory processing and neurobehavioral health outcomes. In this study, we hypothesize that modulation of vitamin D signaling during brain development disrupts molecular pathways associated with sensory processing. Our hypothesis is supported by preliminary data¹ demonstrating that systemic disruption of vitamin D receptor (VDR) signaling during neurodevelopment causes specific and persistent sensorimotor defects in larval zebrafish. To comprehensively define molecular mechanisms of vitamin D-mediated brain development, here we propose to analyze the transcriptome (Aim 1) and metabolome (Aim 2) in our developmental vitamin D deficiency model zebrafish larvae. These analyses will enable future studies to establish causal links between VDR function, neural development, and sensory processing, informing this growing global nutritional epidemic.

PI –Aura Ankita Mishra (Psychology, CHASS)

Co-I –Cathrine Hoyo (Biological Sciences, COS)

Abstract: This study will examine how differential patterns of maternal adversities (i.e., social, behavioral, and environmental) before and during pregnancy influence epigenomic alterations among infants with implications for their lifelong health. Data come from the Stress and Health in Pregnancy Study and includes measures of maternal adversity exposure across multiple contextual levels and assesses cellular epigenetic markers. Identifying which specific clusters of adversity accumulations are most deleterious for child outcomes can lead to the implementation of prevention strategies to improve lifelong health. Such interventions may include therapeutic and lifestyle approaches for social and behavioral adversities and overall reduction in children’s exposure to toxic metals through environmental monitoring and medical treatments. Moreover, the cellular markers assessed in this research can serve as precursors for lifelong health for children even before health symptoms are apparent. 

PI – Caiti Heil (Biological Sciences, COS)

Co-I – Tate Paulette (History, CHASS)

Abstract: Fermentation is one of our oldest biotechnological tools, enhancing food safety, preservation, flavor, and textures. Various human cultures have identified ways to preserve a “starter,”  a mix of microorganisms, that can be used as an inoculum for various fermentation products. One such method involves the desiccation, or drying out, of the starter, as evidenced by examples from “qu” in China, “kveik” in Scandinavia, and potentially “bappir” in ancient Mesopotamia. Across three thousand years of history, the beer brewers of ancient Mesopotamia employed two key ingredients (alongside a range of others): malted barley and another product known as bappir in the Sumerian language. Despite more than a century of discussion, however, specialists do not agree on the interpretation of this key brewing ingredient. One common theory argues that bappir was a dried-out sourdough starter–that is, a community of bacteria and yeast that ferments grains. However, most organisms, including those found in sourdough, are very sensitive to desiccation, which causes hyperosmotic stress, protein misfolding and aggregation, metabolic arrest, membrane disruptions, and often lethality. Our work seeks to answer a key fermentation mystery: how does desiccation influence the microbial community present in a sourdough (potentially akin to bappir), and how does this in turn affect beer fermentation? We will use experimental evolution of sourdoughs subjected to cycles of desiccation, and metabarcoding and metagenomics to characterize how desiccation alters the microbial community of sourdough. We will then use our experimentally evolved sourdough to brew beer, guided by ingredient ratios preserved in administrative records from the ancient city of Girsu in Iraq (c. 2400 BC) to  understand if desiccated sourdough is a plausible interpretation of bappir. Beyond aiding us in understanding the history of brewing in ancient Mesopotamia, this work is essential in understanding desiccation tolerance, a key ecological trait in microorganisms, and has relevance for a number of industrial purposes today.

Advisor: Ritwick Ghosh

Title: Ethical Approaches to Bridging Indigenous and Western Knowledges for Inclusive Governance of Environmental Biotechnologies

Advisor: Rafael Guerrero

Title:  Challenges and applications of genetic risk stratification in

maternal health

Advisor: Deyu Xie

Title: Characterization of a second Cytochrome P450 Reductase enzyme in Artemisia annua and its contributions to the medicinal production of artemisinin.

PI – Yang Zhang (Textile Engineering, Chemistry and Science, TEX)

Co-Is – Caroline Laplante (Molecular Biomedical Sciences CVM), Dongkuan Xu (Computer Science, COE)

Abstract: Single-molecule localization microscopy (SMLM), a Nobel-winning super-resolution imaging technology enables the study of molecular organization and dynamics in living systems beyond current capabilities of fluorescence microscopy with sub-10-nm resolution. Yet its widespread impact has been limited by technical complexity and massive data volumes, which can reach terabytes per day and require months of analysis. This project addresses these barriers by creating an integrated platform that combines advanced SMLM imaging with a scalable, interpretable multiple agent artificial intelligence (AI) system. A start-of-art SMLM system will capture molecular motions, interactions, and physicochemical states, while specialized computational agents will automate denoising, detection, clustering, and tracking. Explainability modules and a human language interface will lower barriers for biomedical researchers and foster human–AI collaboration. The platform will be validated in mammalian cells and insects. The result will be a broadly accessible infrastructure that accelerates biomedical discovery and establishes new models for human-AI scientific workflows.

PI – Natalia Duque-Wilckens (Biological Sciences, COS)

Co-Is – Michele Battle (Molecular Biomedical Sciences CVM), David Aylor (Biological Sciences, COS)

Abstract: Mast cells (MCs) are innate immune cells distributed throughout the body that play crucial roles in host defense and tissue homeostasis. However, when dysregulated, MCs contribute to a wide range of inflammatory and multisystem disorders—from allergic disease to chemical intolerance, multiple sclerosis, and emerging links with neurodevelopmental and mood disorders. Alarmingly, disorders associated with MC dysfunction have increased dramatically in recent decades, suggesting that, beyond established genetic influences, environmental factors may be altering MC function. We found that developmental exposure to Firemaster® 550 (FM550)—a widely used flame retardant associated with allergic, inflammatory, and neurobehavioral effects—induces persistent MC hyperreactivity in vivo, driving exaggerated sickness and inflammatory responses to immune challenges. Similar effects are observed in vitro in bone-marrow-derived mast cells (BMMCs) from adults developmentally exposed to FM550, which show increased granule storage, elevated release of inflammatory mediators, and heightened sensitivity to immune, chemical, and neuron-derived stimuli. Because the bone marrow is the primary source of MC progenitors postnatally, these findings suggest that developmental FM550 exposure reprograms MCs at the progenitor level, priming them for hyperresponsiveness even before tissue-specific differentiation. However, the underlying mechanisms remain unknown. This proposal aims to define the epigenetic basis of developmental FM550-induced MC reprogramming by performing whole-genome bisulfite sequencing (WGBS) and assay for transposase-accessible chromatin sequencing (ATAC-seq) in BMMCs from adult male and female mice developmentally exposed to FM550 or control conditions. Integration of these datasets will, for the first time, reveal the epigenetic architecture underlying MC reprogramming by FM550 exposure—laying the groundwork for understanding how early-life environmental exposures durably shape immune function and disease vulnerability across the lifespan.

PI – Daniel Merselis (Biological Sciences, COS)

Co-Is – Luke Tucker (Lampe Joint Department of Biomedical Engineering, UNC/NCSU)

PI – Zhuyang Lin (Mathematics, COS)

Co-Is – Yafan Zhang (Bioinformatics, COS)

Abstract: Cell–cell communication (CCC) is a fundamental mechanism that enables multicellular systems to coordinate functions and maintain homeostasis, primarily driven by ligand–receptor interactions (LRIs). In tumor cells, CCC also operates extensively within cancer cell–cell and autocrine circuits. However, current expression-based approaches for inferring CCC can reconstruct communication networks but fail to capture how mutation-induced changes in binding affinity (ΔΔG) physically influence effective signaling strength, thereby limiting our understanding of how mutations reshape communication networks and modulate drug responses. To address this limitation, we propose a multiscale framework that integrates (i)
affinity changes (ΔΔG)inkeyligand–receptor pairs caused by cancer associated mutations, predicted through a structure informed, physics-driven, and interpretable modeling framework, and (ii) communication alterations (ΔCCC) inferred from expression data across different cell lines, mutational backgrounds, and drug treatment or time-point conditions. By systematically comparing the direction and magnitude of ΔΔG and ΔCCC, we aim to elucidate how mutations reprogram signaling networks and impact drug responsiveness. Within a unified data system, cross-condition CCC network analyses will identify significantly altered communication pathways, while ΔΔG values will serve as external mechanistic evidence to evaluate their concordance through correlation analysis, robust regression, and statistical significance testing. The resulting method will be implemented as an open-source tool for integrative ΔΔG–ΔCCC comparative analysis, enabling systematic assessment of mutation-driven perturbations in cellular communication. Applied to diverse cancer cell lines with distinct mutational landscapes and drug treatments, this framework will reveal key communication differences between drug-sensitive and drug-resistant phenotypes and uncover how mutations or drugs rewire signaling pathways and gene regulatory programs. Overall, this study establishes a quantitative framework for system-level modeling of cancer signaling and drug response mechanisms, extending mutation effect research from the molecular to the systems level and providing testable hypotheses for experimental validation, target prioritization, and precision therapeutic strategies.