Biology subjects

Harris, C. M.

Publications and source records attributed to Harris, C. M..

7 recordsLinked to original sources

bioRxiv2026

Lipid Hydrogen Stable Isotope Probing Reveals Decadal-Scale Generation Times for Archaea in Hot Spring Sediments

Quantifying the lipid biosynthesis rate of archaea in hot spring sediments is necessary to estimate their generation times and environmental significance, with implications for modern biogeochemical cycling and astrobiology. Here, we performed lipid hydrogen stable isotope probing (LH-SIP) experiments on sediments collected from two high-temperature, suboxic, circumneutral hot springs in Yellowstone National Park (USA) and El Tatio Geyserfield (Chile). We determined the incorporation rate of 2H2O into intact polar lipids (IPLs) during short-duration, ex situ incubations, which provides a taxon- and metabolism-agnostic quantification of biosynthesis under near-natural conditions. We targeted isoprenoid glycerol dialkyl glycerol tetraether lipids (iGDGTs) and recovered structures with 0 to 7 cyclopentyl moieties from both springs. We observed minor 2H-uptake into archaeal IPL-iGDGT-derived biphytanes in spring sediments in Yellowstone, corresponding to decadal-scale apparent generation times (16 +/- 3 years), and no detectable uptake in El Tatio sediments, where lipid turnover was slower than could be resolved under the experimental conditions (maximum resolvable apparent generation times ~ 42 +/- 21 years). We conclude that these slow apparent generation times likely reflect substantial dilution by a large standing IPL pool and/or recycling or re-functionalization of relict lipid components, rather than equivalently slow rates of archaeal cell division. These are the first estimates of archaeal lipid production rates in terrestrial hydrothermal systems using LH-SIP incubations and provide critical constraints for interpreting archaeal lipids in modern systems and ancient hot spring deposits.

microbiology↗

bioRxiv2025

Design of SARS-CoV-2 RBD Immunogens to Focus Immune Responses Towards Conserved Coronavirus Epitopes

SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach towards developing superior, variant-proof vaccines is to engineer immunogens that preferentially elicit antibodies with broad cross-reactivity against SARS-CoV-2 and its variants by targeting conserved epitopes on spike. The inner and outer faces of the Receptor Binding Domain (RBD) are two such conserved regions targeted by antibodies that recognize diverse human and animal coronaviruses. To promote the elicitation of such antibodies by vaccination, we engineered "resurfaced" RBD immunogens that contained mutations at exposed RBD residues outside the target epitopes. In the context of pre-existing immunity, these vaccine candidates aim to disfavor the elicitation of strain-specific antibodies against the immunodominant Receptor Binding Motif (RBM) while boosting the induction of inner and outer face antibodies. The engineered resurfaced RBD immunogens were stable, lacked binding to monoclonal antibodies with limited breadth, and maintained strong interactions with target broadly neutralizing antibodies. When used as vaccines, they limited humoral responses against the RBM as intended. Multimerization on nanoparticles further increased the immunogenicity of the resurfaced RBDs immunogens, thus supporting resurfacing as a promising immunogen design approach to rationally shift natural immune responses to develop more protective vaccines.

immunology↗

bioRxiv2024

Lipid hydrogen isotope compositions primarily reflect growth water in the model archaeon Sulfolobus acidocaldarius

The stable hydrogen isotope composition ({delta}2H) of lipid biomarkers can track environmental processes and remain stable over geologically relevant time scales, enabling studies of past climate, hydrology, and ecology. Most research has focused on lipids from the domain Eukarya (e.g., plant waxes, long-chain alkanes), and the potential of prokaryotic lipid biomarkers from the domain Archaea to offer unique insights into environments not captured by eukaryotic lipids remains unclear. Here, we investigate the H-isotope composition of biphytanes in Sulfolobus acidocaldarius, a model thermoacidophile and obligate heterotroph. We conducted a series of experiments that varied temperature, pH, shaking rate, electron acceptor availability, or electron donor flux. From these experiments, we quantified the lipid/water H-isotope fractionation (2{varepsilon}L/W) values for core biphytane chains derived from tetraether lipids. The 2{varepsilon}L/W values are consistently negative (-230 to - 180 {per thousand}) and are relatively invariant across all experiments despite a 20-fold change in doubling times and 2-fold change in lipid cyclization. The magnitude and relative invariance of 2{varepsilon}L/W values are consistent with studies on other heterotrophic archaea and suggests archaeal lipids may be faithful recorders of the {delta}2H composition of growth water. Our study highlights the potential of archaeal lipid {delta}2H as a hydrological proxy, offering new insights into environments where traditional proxies, such as plant-derived lipids, are not available, including extreme environments and extraterrestrial settings. ImportanceReconstructing past climates is crucial for understanding Earths environmental history and its responses to changing conditions. This study examines Sulfolobus acidocaldarius, a thermoacidophilic archaeon that thrives in extreme environments like hot springs. These microorganisms incorporate hydrogen water in the growth environment into membrane lipids, creating hydrogen isotope signatures that can reflect hydroclimate conditions. Our findings show that these hydrogen isotope ratios remain consistent even under varying temperature, pH, oxygen levels, and electron donor fluxes, indicating a stable fractionation between lipids and water. This invariance suggests that S. acidocaldarius lipids could serve as a robust proxy for reconstructing ancient water H-isotope values, especially in extreme environments where traditional proxies, such as plant waxes, are absent. This research has broader implications for planetary-scale reconstructions, including potential applications in studying past climates on other planets, such as Mars, where similar microorganisms may have existed in hydrothermal conditions.

microbiology↗

bioRxiv2024

Environmental controls on crenarchaeol distributions in hydrothermal springs

Thermophilic archaea synthesize cellular membranes composed primarily of isoprenoid glycerol dibiphytanyl glycerol tetraethers (iGDGTs). Cells can adjust the packing of their lipids by increasing the number of cyclopentyl rings during lipid synthesis, thereby decreasing membrane permeability and fluidity to maintain cellular function at high temperature, acidic pH, or nutrient limitation. Archaea of the class Nitrososphaeria synthesize an iGDGT, crenarchaeol, with four cyclopentyl rings and a cyclohexyl ring, the function of which is unknown. Structural modeling suggests the cyclohexyl ring may increase membrane fluidity, potentially optimizing membranes for mesophilic conditions. To begin to investigate this hypothesis, iGDGT composition was quantified in forty-one thermal springs in Yellowstone National Park (YNP), USA, and contextualized within a global thermal spring iGDGT compilation with pH values of 1.1 to 10.1 and temperatures of 16 to 95{degrees}C. pH was the strongest predictor of both crenarchaeol relative abundance and the number of cyclopentyl rings per iGDGT. Crenarchaeol relative abundance exhibited a nonlinear relationship with pH and temperature, with highest relative abundances at pH 7.4 and 46{degrees}C, then decreasing above and below these values. These observations are consistent with the hypothesis that the cyclohexyl ring of crenarchaeol optimizes archaeal cellular membranes for circumneutral and moderate temperature environmental conditions. ImportanceArchaea change the composition of their membrane lipids to alter the fluidity of their membranes to maintain cell homeostasis when confronted with environmental stress. Some archaea of the class Nitrososphaeria produce a lipid, crenarchaeol, with a unique six-membered ring, the effect of which on archaeal membrane dynamics remains unknown. In this study, we identify pH as the most important geochemical variable for archaeal membrane response in Yellowstone National Park thermal springs. In addition, the lipid distributions indicate that crenarchaeol production is highest in circumneutral and mesophilic environments. The YNP results are supported by similar trends across global thermal springs.

microbiology↗

bioRxiv2023

The hydrogen isotope signatures of autotrophy versus heterotrophy recorded in archaeal tetraether lipids

The stable hydrogen isotope composition of archaeal lipids is emerging as a potential paleoenvironmental proxy, adding to the well-established application of plant leaf wax-derived n-alkanes in paleohydrological reconstruction. A handful of studies reported relatively invariant and depleted hydrogen isotope compositions for archaeal lipids despite the range of different organisms and growth conditions explored. However, how modes of metabolism and physiological state (growth phase) affect the hydrogen isotope signatures of archaeal lipids remains poorly understood, limiting our ability to interpret archaeal lipid biomarker records from the environment. Here we conducted water isotope label experiments with a metabolically flexible and well-studied model archaeon Archaeoglobus fulgidus and quantified the hydrogen isotope fractionation between lipids and water in response to different carbon substrates and electron donor-acceptor pairs. The 2H/1H fractionation between lipids and water ({varepsilon}L/W) was overall negative, ranging from -280 to -226 {per thousand}, and overlapped with the ranges observed for other archaea in previous studies. Isotope flux-balance model results suggest that [≥]80 % and [≥]50 % of lipid-bound H in A. fulgidus cultures directly reflect water isotope compositions (i.e., not via organic substrate or H2) during autotrophy and heterotrophy, respectively. The model results also suggest the final saturation during isoprenoid lipid biosynthesis catalyzed by a flavoenzyme geranylgeranyl reductase likely contributes to the large 2H/1H fractionation observed in this study, consistent with previous isotope flux-balance model results for a different archaeon. Finally, we synthesized available data to compare {varepsilon}L/W patterns across all three domains of life: Bacteria, Archaea and Eukarya. Emerging patterns between archaeal and eukaryotic lipids are consistent with the notion of highly fractionating geranylgeranyl reductase, and the patterns between archaeal and bacterial lipids suggest that the general state of energy limitation may also contribute to large, negative values of {varepsilon}L/W observed in prokaryotic lipids. Altogether, these findings lend further support for the potential of archaeal lipid {varepsilon}L/W as a paleohydrological proxy and provide a broader insight into the 2H/1H fractionation mechanisms potentially shared among prokaryotic and eukaryotic lipid biomarkers.

microbiology↗

bioRxiv2021

CarboGrove: a resource of glycan-binding specificities through analyzed glycan-array datasets from all platforms

The volume and value of glycan-array data are increasing, but no common method and resource exists to analyze, integrate, and use the available data. To meet this need, we developed a resource of analyzed glycan-array data called CarboGrove. Building on the ability to process and interpret data from any type of glycan array, we populated the database with the results from 35 types of glycan arrays, 13 glycan families, 5 experimental methods, and 19 laboratories or companies. In meta-analyses of glycan-binding proteins, we observed glycan-binding specificities that were not uncovered from single sources. In addition, we confirmed the ability to efficiently optimize selections of glycan-binding proteins to be used in experiments for discriminating between closely related motifs. CarboGrove yields unprecedented access to the wealth of glycan-array data being produced and powerful capabilities for both experimentalists and bioinformaticians. TeaserWe introduce a resource that allows researchers to find, compare, study, and integrate analyses from all types of glycan-array data.

bioinformatics↗

bioRxiv2018

Baseline corticosterone does not reflect iridescent plumage traits in female tree swallows

The production of high quality secondary sexual traits can be constrained by trade-offs in the allocation of energy and nutrients with other metabolic activities, and is mediated by physiological processes. In birds, the factors influencing male plumage quality have been well studied; however, factors affecting female plumage quality are poorly understood. Furthermore, it remains uncertain which physiological traits mediate the relationship between body condition and ornaments. In this three-year study of after-second-year female tree swallows (Tachycineta bicolor), we investigated (1) the relationship between baseline corticosterone near the end of the brood-rearing period (CORTBR) and feather colour characteristics (hue, saturation, brightness) the following year, and (2) the relationship between baseline corticosterone measured during incubation (CORTI) and brood rearing (CORTBR), and feather colour in the same year. To control for reproductive effort, we included reproductive parameters as covariates in all analyses. In this first study between CORT and the plumage colour characteristics of a species bearing iridescent feathers, we did not find any relationship between CORTBR and the colour of subsequently-produced feathers, nor did we find any relationship between CORTI and the colour of feathers displayed during that breeding season. If CORT levels at the end of breeding carry over to influence the immediately subsequent moult period as we expect, our results generally indicate that structural plumage quality may not be as sensitive to circulating CORT levels compared to carotenoid-based colouration. Future studies, particularly those employing experimental manipulations of CORT during moult in species with iridescent traits, are necessary to fully determine the role glucocorticoids play in mediating the quality of secondary sexual characteristics.

zoology↗