Biology subjects

Bessler, S.

Publications and source records attributed to Bessler, S..

7 recordsLinked to original sources

bioRxiv2025

TSP1/TGF-β1 drives arachidonic acid metabolism to orchestrate neutrophil swarming

Neutrophil swarming has emerged as a conserved multicellular behaviour observed across tissues and pathological contexts. Yet, the molecular cues and the spatially coordinated cellular circuits that drive the process of neutrophil swarming leading to cluster formation remain poorly understood. Here, we combine spatial proteomics and lipid profiling in a model of urinary tract infection to define the epithelial-immune circuits driving neutrophil cluster formation. We identify thrombospondin-1 (TSP1)-mediated activation of transforming growth factor beta 1 (TGF-{beta}1) as key epithelial signal licensing neutrophil clustering and enhancing bacterial control. Spatial lipid analysis further reveals that TSP1/TGF-{beta}1 signalling locally activates arachidonic acid metabolism in epithelial neutrophils, with 5-lipoxygenase dependent leukotriene synthesis required for swarm formation and infection clearance. These findings uncover a spatially coordinated defence mechanism in which epithelial-derived TSP1/TGF-{beta}1 engages neutrophil lipid metabolism to orchestrate neutrophil swarming behaviour and reinforce antibacterial immunity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/688397v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@114ea92org.highwire.dtl.DTLVardef@345244org.highwire.dtl.DTLVardef@10520baorg.highwire.dtl.DTLVardef@1a7c0fe_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

immunology↗

bioRxiv2025

Single-cell mass spectrometry imaging combined with immunofluorescence reveals neutrophil heterogeneity in inflammation

Multimodal single-cell approaches allow for a holistic analysis of complex biological systems. In this study, we developed a novel single-cell analysis pipeline integrating immunofluorescence-based protein with mass spectrometry imaging-based lipid analysis of circulating human neutrophils. The combination of both modalities identified the emergence of pathogenic neutrophils in liver cirrhosis patients thus epitomizing the potential of this technology to reveal cellular phenotypes in health and disease.

immunology↗

bioRxiv2024

Histology-Guided Single-Cell Mass Spectrometry Imaging using Integrated Bright-field and Fluorescence Microscopy

The rapidly evolving field of spatial biology revolves around the analysis of cells in their native microenvironment. This analysis can include morphological features, the presence of specific antigens or gene expression. To add another layer of information, recent methodological advances in matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) now enable the untargeted analysis of lipids and metabolites at subcellular resolution. The integration of MALDI-MSI at the single-cell level with established optical modalities, however, relies on an accurate yet intricate co-registration. Here, we describe the integration of bright-field and fluorescence microscopy into a prototype ion source of a state-of-the art MALDI-MSI instrument to obtain lipid and fluorescence microscopy-derived information from the same specimen, hence with intrinsic spatial correlation. We demonstrate the potential of the combined mass spectrometric and optical single-cell analysis on three examples. This includes the visualization of intracellular lipid distributions in macrophages, the introduction of pre-MALDI immunofluorescence staining on the example of murine cerebellum, and the heterogeneity of lipid profiles of tumor infiltrating neutrophils correlated to their individual microenvironments. Overall, the achieved tight correlation of single-cell lipid profiles with morphologic features and protein expression patterns constitutes a powerful resource for cell biology.

cell biology↗

bioRxiv2024

msiFlow: Automated Workflows for Reproducible and Scalable Multimodal Mass Spectrometry Imaging and Immunofluorescence Microscopy Data Processing and Analysis

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and immunofluorescence microscopy holds great potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing open-source software solutions for analysis of MALDI MSI data are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries across interdisciplinary research fields. Here we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data. msiFlow integrates all necessary steps from import and pre-processing of raw MALDI MSI data to visual analysis output, as well as registration, along with state-of-the-art and newly developed algorithms, into automated workflows. Using msiFlow, we unravel the molecular heterogeneity of leukocytes in infected tissues by spatial regulation of ether-linked phospholipids containing arachidonic acid. We anticipate that msiFlow will facilitate the broad applicability of MSI in the emerging field of multimodal imaging to uncover context-dependent cellular regulations in disease states.

bioinformatics↗

bioRxiv2019

A meta-analysis reveals temperature, dose, life stage, and taxonomy influence host susceptibility to a fungal parasite

Complex ecological relationships, such as host-parasite interactions, are often modeled with laboratory experiments. However, some experimental laboratory conditions, such as temperature or infection dose, are regularly chosen based on convenience or convention and it is unclear how these decisions systematically affect experimental outcomes. Here, we conducted a meta-analysis of 58 laboratory studies that exposed amphibians to the pathogenic fungus Batrachochytrium dendrobatidis (Bd) to better understand how laboratory temperature, host life stage, infection dose, and host species affect host mortality. We found that host mortality was driven by thermal mismatches: hosts native to cooler environments experienced greater Bd-induced mortality at relatively warm experimental temperatures and vice versa. We also found that Bd dose positively predicted Bd-induced host mortality and that the superfamilies Bufonoidea and Hyloidea were especially susceptible to Bd. Finally, the effect of Bd on host mortality varied across host life stages, with larval amphibians experiencing lower risk of Bd-induced mortality than adults or metamorphs. Metamorphs were especially susceptible and experienced mortality when inoculated with much smaller Bd doses than the average dose used by researchers. Our results suggest that when designing experiments on species interactions, researchers should carefully consider the experimental temperature, and inoculum dose, and life stage and taxonomy of the host species.

ecology↗

bioRxiv2018

Evaluating Improvements to Exposure Estimates from Fate and Transport Models by Incorporating Environmental Sampling Effort and Landscape-level Contaminant Use

AO_SCPCAPBSTRACTC_SCPCAPThe Pesticide in Water Calculator (PWC) is a fate and transport model used by the Environmental Protection Agency and Health Canada to estimate pesticide exposures in lentic freshwater ecosystems and make pesticide registration decisions. We leverage over 600,000 field measurements of 31 common insecticides and herbicides to test whether incorporating environmental sampling effort (number of times a pesticide is sampled) and landscape-level contaminant use (national application amount) can improve PWC validation and prediction, respectively. We found that maximum measured concentrations of 38% of herbicides and 42% of insecticides exceeded maximum estimated environmental concentrations (EECs) generated by the PWC, suggesting that EECs often do not represent worst-case exposure. For lentic systems, variance in pesticide field measurements explained by EECs increased by 50% when sampling effort was included. For lotic systems, variance explained increased by only 4%, most likely because lotic systems are sampled over 4.9 times as much as lentic systems. Including landscape-level use more than doubled the ability of the PWC to predict maximum pesticides concentrations in lentic systems. Exposure characterization in risk assessment can be improved by including sampling effort in model validation and landscape-level use in predictions, thus providing more defensible environmental standards and regulations.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC=\"FIGDIR/small/472969_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (122K):\norg.highwire.dtl.DTLVardef@601b22org.highwire.dtl.DTLVardef@19591e5org.highwire.dtl.DTLVardef@9d6196org.highwire.dtl.DTLVardef@71c96c_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2018

Impacts of thermal mismatches on chytrid fungus Batrachochytrium dendrobatidis prevalence are moderated by life stage, body size, elevation and latitude

Global climate change is increasing the frequency of unpredictable weather conditions; however, it remains unclear how species-level and geographic factors, including body size and latitude, moderate impacts of unusually warm or cool temperatures on disease. Because larger hosts and lower-latitude hosts generally have slower acclimation times, we hypothesized that their disease susceptibility increases under \"thermal mismatches\", or differences between baseline climate and the temperature during surveying. Here, we examined how thermal mismatches interact with body size, life stage, habitat, latitude, elevation, phylogeny, and IUCN conservation status to predict infection prevalence of the chytrid fungus Batrachochytrium dendrobatidis (Bd) in a global analysis of 38,967 amphibian hosts. As hypothesized, we found that the susceptibility of larger hosts and hosts from lower latitudes was strongly influenced by thermal mismatches. Furthermore, hosts of conservation concern are more susceptible than others following thermal mismatches, suggesting that thermal mismatches might have contributed to recent amphibian declines.\n\nData Accessibility StatementShould the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository such as Dryad or Figshare and the data DOI will be included at the end of the article.

ecology↗