Biology subjects

Lax, S.

Publications and source records attributed to Lax, S..

6 recordsLinked to original sources

bioRxiv2025

Tissue architecture and immune niches govern ctDNA release in colorectal cancer

Circulating tumor DNA (ctDNA) is central to liquid biopsy-based cancer detection, yet its release into the bloodstream varies widely and remains poorly understood. To define the tissue-level determinants of ctDNA shedding in colorectal cancer (CRC), we integrated tumor-informed plasma sequencing with detailed histopathology, immunophenotyping, spatial transcriptomics, and in situ mutation detection in resectable stages (I-III). ctDNA detectability increased with tumor burden, and high ctDNA shedders exhibited a distinct architectural and microenvironmental phenotype characterized by expanded necrotic pseudolumina, frequent epithelial barrier disruption, and dense myeloid infiltration. Spatial profiling revealed stress-associated malignant programs and a myeloid-rich immune-luminal niche. In situ sequencing confirmed plasma-detected mutations within pseudoluminal debris, identifying these structures as focal reservoirs of shed DNA. These findings provide a mechanistic framework linking tissue architecture, immune remodelling, and spatially organized cell death to ctDNA release with implications for refining liquid biopsy applications.

cancer biology↗

bioRxiv2025

Spatiotemporal Microbial Ecoevolutionary Dynamics on the International Space Station

This study presents the most comprehensive spatiotemporal analysis of the ISS microbiome to date. Over a seven-year period, 184 surface samples were collected for live/dead metagenomic profiling, phenotypic characterization of antimicrobial resistance (AMR) and virulence among 102 cultured isolates, and metagenome-assembled genome (MAG) analysis to evaluate evolutionary selection pressures. Despite ecological stability, comparative genomics revealed ongoing microevolution through lateral gene transfer and selection for traits (e.g., radiation resistance and biocide tolerance). Importantly, predictions of AMR and virulence frequently misaligned with experimental outcomes, underscoring the need for functional validation. This dataset highlights a stable core microbiome that persists across years, punctuated by localized adaptation and gene flow. The ISS microbiome exemplifies both ecological resilience and microevolutionary innovation that can inform risk management for long-duration spaceflight.

microbiology↗

bioRxiv2022

Strong Ethanol- and Frequency-Dependent Ecological Interactions in a Community of Wine-Fermenting Yeasts

Natural wine fermentation is carried out by the complex consortia of microorganisms native to grapes and winery equipment, rather than by inoculation with industrial yeast strains. While this diversity of yeasts can result in an increased repertoire of wine flavors and aromas, it can also result in the inhibition of Saccharomyces cerevisiae, which is uniquely able to withstand the high ethanol and low resource conditions in the end stages of fermentation. Understanding how yeast species interact with each other within the wine-fermenting community, and disentangling the importance of these ecological interactions from the environmental impacts on growth rates, is key to developing synthetic communities that can provide the sensory benefits of natural fermentation while lowering the risk of stuck ferments. While numerous studies have characterized the dynamics of experimental fermentations, carried out by both synthetic and natural communities, it is difficult to infer ecological interactions from transient population dynamics. Here, we co-culture all pairwise combinations of five commonly isolated wine-fermenting yeasts at various ethanol concentrations. We show that these pairwise outcomes are a strong function of ethanol concentration, with frequency-dependent bistable interactions common at low alcohol and an increasingly transitive competitive hierarchy developing as alcohol increases. We also show that these pairwise outcomes are predictive of five-species community outcomes, and that frequency dependence in pairwise interactions can propagate to alternative states in the full community, highlighting the importance of species abundance as well as composition. We also observe that monoculture growth rates as a function of ethanol are only weakly predictive of competitive success, highlighting the need to incorporate ecological interactions when designing synthetic communities for optimal fermentation performance.

ecology↗

bioRxiv2019

Higher Temperatures Generically Favor Slower-Growing Bacterial Species in Multispecies Communities

Temperature is among the cardinal environmental variables which determine the composition and function of microbial communities. Many culture-independent studies have characterized communities that are affected by changing temperatures, either due to seasonal cycles1-3, long-term warming4-6, or latitudinal/elevational gradients7-8. However, a predictive understanding of how microbial communities respond to such changes in temperature is still lacking, partly because it is not obvious which aspects of microbial physiology determine whether a species should benefit from temperature alteration. Here, we incorporate how microbial growth rates change with temperature to a modified Lotka-Volterra competition model9, and predict that higher temperatures should generically favor slower-growing species in a bacterial community. We experimentally confirm this prediction in pairwise cocultures assembled from a diverse set of species, and we show that these changes to pairwise outcomes with temperature are also predictive of changing outcomes in three-species communities, suggesting our theory may propagate to more complex assemblages. Our results demonstrate that it is possible to predict how bacterial communities will shift with temperature knowing only the growth rates of the community members. These results provide a testable hypothesis for future studies of more complex, natural communities, and we hope that this work will help bridge the gap between ecological theory and the complex dynamics observed in metagenomic surveys.

ecology↗

bioRxiv2019

Microbial Similarity between Students in a Common Dormitory Environment Reveals the Forensic Potential of Individual Microbial Signatures

The microbiota of the built environment is an amalgamation of both human and environmental sources. While human sources have been examined within single-family households or in public environments, it is unclear what effect a large number of cohabitating people have on the microbial communities of their shared environment. We sampled the public and private spaces of a college dormitory, disentangling individual microbial signatures and their impact on the microbiota of common spaces. We compared multiple methods for marker gene sequence clustering, and found that Minimum Entropy Decomposition (MED) was best able to distinguish between the microbial signatures of different individuals, and was able to uncover more discriminative taxa across all taxonomic groups. Further, weighted UniFrac- and random forest-based graph analyses uncovered two distinct spheres of hand or shoe associated samples. For hand-associated samples, connection between cliques was enriched for hands, implicating them as a primary means of transmission. By contrast, shoe-associated samples were found to be freely interacting, with individual shoes more connected to each other than to the floors they interact with. Individual interactions were highly dynamic, with groups of samples originating from individuals clustering freely with other individuals, while all floor and shoe samples consistently clustered together.\n\nImportanceHumans leave behind a microbial trail, regardless of intention. This may allow for the identification of individuals based on the microbial signatures they shed in built environments. In a shared living environment, these trails intersect, and through interaction with common surfaces may become homogenized, potentially confounding our ability to link individuals to their associated microbiota. We sought to understand the factors that influence the mixing of individual signatures, and how best to process sequencing data to best tease apart these signatures.

ecology↗

bioRxiv2018

Microbial and Metabolic Succession on Common Building Materials Under High Humidity Conditions

Despite considerable efforts to characterize the ecology of bacteria and fungi in the built environment (BE), the metabolic mechanisms underpinning their colonization and successional dynamics remain unclear. Here, we applied bacterial/viral particle counting, qPCR, 16S and ITS rRNA amplicon sequencing, and metabolomics to longitudinally characterize the ecological dynamics of four commonly used building materials maintained at high humidity conditions (~94% RH). We varied the natural inoculum provided to each material by placing them in different occupied spaces, and we wet the surface of half of the samples of each material to simulate a flooding event. As expected, different materials showed different bacterial and viral particle abundance, with wet materials having higher growth rates and lower alpha diversity compared to non-wetted materials. Wetting described the majority of the variance in bacterial, fungal and metabolite structure, and material type only influenced bacterial and metabolic diversity, while location of inoculation was only weakly associated with bacterial and fungal beta diversity. Metabolites indicative of microbial activity were identified, as were those that were native to the surface material. Glucose-phosphate was abundant on all materials (except mold-free gypsum) and was correlated with Enterobacteriaceae, which could indicate a potential bacterial nutrient source. A compound consistent with scopoletin, a plant metabolite with antimicrobial activity, was significantly negatively correlated with Bacillus and positively correlated with Pseudomonas and enriched in medium density fiberboard (MDF) materials. In wet samples, the alkaloids nigragillin and fumigaclavine C, both with antimicrobial properties, were significantly positively correlated with the fungal phylum Ascomycota. Nigragillin, was also negatively correlated with Bacillus and Pseudomonas abundance. Thiabendazole and azoxystrobin (anti-fungal compounds) were highly abundant on mold-resistant gypsum wallboard and likely directly influenced the decreased fungal growth observed on this material. The mold-resistant gypsum material also showed a significant increase in bacterial alpha diversity, and bacterial and viral particle abundance, as well as a decrease in metabolite diversity, likely a result of reduced fungal growth. Penicillium taxa were positively correlated with thiabendazole, which suggested the persistence of resistant strains. Also, specific to the wet samples, Bacillus abundance was positively correlated with the azoxystrobin, suggesting bi-directional competitive adaptation, and positively correlated with metabolites known to interfere with Pseudomonas biofilm formation, which could explain the anti-correlation between these taxa. As expected, high moisture conditions enabled faster growth of inoculating microorganisms, whose composition, chemistry, and competition was shaped by surface material, suggesting that both fungal and bacterial growth need to be considered when determining the impact of dampness in built environments.

microbiology↗