Engineering topics

Hixson, Kim K.

Publications and source records attributed to Hixson, Kim K..

6 records

DOE OSTI2026

Circadian immunometabolic states impart a temporal response to SARS-CoV-2 spike proteins in mammalian macrophages

Circadian rhythms, the 24-hour cycles that tune organismal physiology to the daily rhythms of light and dark, optimally organize cellular processes such as metabolism and mitochondrial function. In mammals, macrophage functions are regulated by these 24-hour circadian rhythms such that the immunometabolic response is coordinated across the day, consolidating macrophage physiology into temporally distinct phases to time the cellular immune response. However, while it is known that there are time-of-day specific responses to stress in a macrophage, little has been done to determine if circadian regulation coordinates the response of a macrophage to real-world pathogens. Importantly, key proteins in the response to viral infection have been found to be under circadian control, and time of day of application is known to affect the efficacy of vaccinations, including in the case of the COVID-19 virus. Therefore, to investigate if the circadian regulation of macrophage physiology imparted a time-of-day response to viral exposure, we exposed primary mouse and human macrophages to the SARS-CoV-1 and CoV-2 spike proteins at different times over the circadian day. To establish a time-of-day effect, we performed a multi-omics analysis and in vitro tissue culture assays examining macrophage responses over circadian time. We found that, conserved across the species, the timing of spike protein exposure dictated two distinct temporal responses which were characterized by hallmarks of immunometabolic suppression and modest inflammatory activation. However, these responses were primarily influenced by central metabolic and mitochondrial changes and not by classical immune activation.

Circadian Biology↗

DOE OSTI2025

Holo-Omics disentangle drought response and biotic interactions among plant, endophyte and pathogen

Holo-omics provide a novel opportunity to study the interactions among fungi from different functional guilds in host plants in field conditions. We address the entangled responses of plant pathogenic and endophytic fungi associated with sorghum when droughted through the assembly of the most abundant fungal, endophyte genome from rhizospheric metagenomic sequences followed by a comparison of its metatranscriptome with the host plant metabolome and transcriptome. The rise in relative abundance of endophytic Acremonium persicinum (operational taxonomic unit 5 (OTU5)) in drought co-occurs with a rise in fungal membrane dynamics and plant metabolites, led by ethanolamine, a key phospholipid membrane component. The negative association between endophytic A. persicinum (OTU5) and plant pathogenic fungi co-occurs with a rise in expression of the endophyte's biosynthetic gene clusters coding for secondary compounds. Endophytic A. persicinum (OTU5) and plant pathogenic fungi are negatively associated under preflowering drought but not under postflowering drought, likely a consequence of variation in fungal fitness responses to changes in the availability of water and niche space caused by plant maturation over the growing season. Our findings suggest that the dynamic biotic interactions among host, beneficial and harmful microbiota in a changing environment can be disentangled by a blending of field observation, laboratory validation, holo-omics and ecological modelling.

Chen, Peilin↗

DOE OSTI2024

RNA-seq and metabolomic analyses of beneficial plant phenol biochemical pathways in red alder

Red alder ( Alnus rubra ) has highly desirable wood, dye pigment, and (traditional) medicinal properties which have been capitalized on for thousands of years, including by Pacific West Coast Native Americans. A rapidly growing tree species native to North American western coastal and riparian regions, it undergoes symbiosis with actinobacterium Frankia via their nitrogen-fixing root nodules. Red alder’s desirable properties are, however, largely attributed to its bioactive plant phenol metabolites, including for plant defense, for its attractive wood and bark coloration, and various beneficial medicinal properties. Integrated transcriptome and metabolome data analyses were carried out using buds, leaves, stems, roots, and root nodules from greenhouse grown red alder saplings with samples collected during different time-points (Spring, Summer, and Fall) of the growing season. Pollen and catkins were collected from field grown mature trees. Overall plant phenol biochemical pathways operative in red alder were determined, with a particular emphasis on potentially identifying candidates for the long unknown gateway entry points to the proanthocyanidin (PA) and ellagitannin metabolic classes, as well as in gaining better understanding of the biochemical basis of diarylheptanoid formation, i.e. that help define red alder’s varied medicinal uses, and its extensive wood and dye usage.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Tripogon loliiformis tolerates rapid desiccation after metabolic and transcriptional priming during initial drying

Abstract Crop plants and undomesticated resilient species employ different strategies to regulate their energy resources and growth. Most crop species are sensitive to stress and prioritise rapid growth to maximise yield or biomass production. In contrast, resilient plants grow slowly, are small, and allocate their resources for survival in challenging environments. One small group of plants, termed resurrection plants, survive desiccation of their vegetative tissue and regain full metabolic activity upon watering. However, the precise molecular mechanisms underlying this extreme tolerance remain unknown. In this study, we employed a transcriptomics and metabolomics approach, to investigate the mechanisms of desiccation tolerance in Tripogon loliiformis , a modified desiccation-tolerant plant, that survives gradual but not rapid drying. We show that T. loliiformis can survive rapid desiccation if it is gradually dried to 60% relative water content (RWC). Furthermore, the gene expression data showed that T. loliiformis is genetically predisposed for desiccation in the hydrated state, as evidenced by the accumulation of MYB, NAC, bZIP, WRKY transcription factors along with the phytohormones, abscisic acid, salicylic acid, amino acids (e.g., proline) and TCA cycle sugars during initial drying. Through network analysis of co-expressed genes, we observed differential responses to desiccation between T. loliiformis shoots and roots. Dehydrating shoots displayed global transcriptional changes across broad functional categories, although no enrichment was observed during drying. In contrast, dehydrating roots showed distinct network changes with the most significant differences occurring at 40% RWC. The cumulative effects of the early stress responses may indicate the minimum requirements of desiccation tolerance and enable T. loliiformis to survive rapid drying. These findings potentially hold promise for identifying biotechnological solutions aimed at developing drought-tolerant crops without growth and yield penalties.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Metabolomic, photoprotective, and photosynthetic acclimatory responses to post‐flowering drought in sorghum

Abstract Climate change is globally affecting rainfall patterns, necessitating the improvement of drought tolerance in crops. Sorghum bicolor is a relatively drought‐tolerant cereal. Functional stay‐green sorghum genotypes can maintain green leaf area and efficient grain filling during terminal post‐flowering water deprivation, a period of ~10 weeks. To obtain molecular insights into these characteristics, two drought‐tolerant genotypes, BTx642 and RTx430, were grown in replicated control and terminal post‐flowering drought field plots in California's Central Valley. Photosynthetic, photoprotective, and water dynamics traits were quantified and correlated with metabolomic data collected from leaves, stems, and roots at multiple timepoints during control and drought conditions. Physiological and metabolomic data were then compared to longitudinal RNA sequencing data collected from these two genotypes. The unique metabolic and transcriptomic response to post‐flowering drought in sorghum supports a role for the metabolite galactinol in controlling photosynthetic activity through regulating stomatal closure in post‐flowering drought. Additionally, in the functional stay‐green genotype BTx642, photoprotective responses were specifically induced in post‐flowering drought, supporting a role for photoprotection in the molecular response associated with the functional stay‐green trait. From these insights, new pathways are identified that can be targeted to maximize yields under growth conditions with limited water.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2023

Editorial: Plant-microbe omics

Omics-based studies have evolved over the past two decades to provide rich datasets from which deeper system-level understanding can be unraveled. Omics technologies (e.g., genomics, transcriptomics, proteomics, and metabolomics) can provide specific molecular insights into plant and microbe fitness, disease states, stress, cell signaling/cell-cell communication, and nutrient exchange, and these molecular observations can be correlated with system phenotype and function. The overall health of plant-microbe systems and their surrounding environments can be assessed, and a greater understanding of processes related to nutrient exchange/cycling, plant disease, and ecosystem homeostasis can now be achieved via the latest approaches to plant-microbe omics analysis.

59 BASIC BIOLOGICAL SCIENCES↗