Biology subjects

Janssen, E.

Publications and source records attributed to Janssen, E..

7 recordsLinked to original sources

bioRxiv2025

Zooplankton feeding behaviour and survival to toxic and non-toxic cyanobacteria during the seasonal bloom progression of a eutrophic lake

Harmful cyanobacterial blooms pose increasing threats to aquatic ecosystems and human health; yet, the role of zooplankton grazing in regulating blooms remains understudied. We investigated the seasonal feeding behaviour and fitness consequences of feeding preferences in natural zooplankton communities for toxic (microcystin-producing) versus non-toxic cyanobacteria across temperature gradients in eutrophic Lake Greifen, Switzerland. We conducted monthly experiments from April to October 2023 to test the grazing behaviour of four zooplankton groups (daphnids, calanoid copepods, cyclopoid copepods, and microzooplankton) exposed to mixed diets of green algae and either toxic or non-toxic Microcystis strains at 15{degrees}C and 25{degrees}C. Contrary to expectations of cyanobacteria avoidance, zooplankton exhibited predominantly non-selective grazing throughout the seasonal succession, consuming both toxic and non-toxic cyanobacteria at similar rates, regardless of temperature. Notably, during the peaks of phytoplankton abundance (April and September), mesozooplankton demonstrated a selective preference for cyanobacteria over green algae, particularly non-toxic strains. Temperature effects were subtle but revealed metabolic constraints: elevated temperatures occasionally triggered selective consumption of cyanobacteria in copepods, while fitness costs (survival) from exposure to toxic species were mostly restricted to transitional bloom periods and high-temperature conditions. These findings suggest that toxic cyanobacteria may not always evade grazing pressure through secondary metabolite deterrent effects. Our results suggest that zooplankton communities can adapt and graze on cyanobacteria regardless of toxicity under the tested conditions, even during bloom conditions. These observations highlight the potential for zooplankton to interact with cyanobacterial populations, which may have implications for bloom prediction and management strategies, particularly under climate warming scenarios. Manuscript HighlightsO_LIZooplankton grazed on toxic and non-toxic cyanobacteria with similar effects across seasons in a eutrophic lake characterised by toxic blooms. C_LIO_LINatural zooplankton communities showed no systematic avoidance of microcystin-producing cyanobacteria. C_LIO_LIHigh temperature effects on feeding selectivity were subtle and taxon-specific. C_LIO_LIFitness costs from exposure to cyanobacteria (including microcystin-producing isolates) were rare and occurred only during transitional bloom periods. C_LIO_LIResults suggest that zooplankton communities may be adapted to cyanobacterial blooms, even when dominated by toxic species. C_LI

ecology↗

bioRxiv2025

Sub-Nanomolar Detection and Discrimination of Microcystin Congeners Using Aerolysin Nanopores

Climate-driven disruptions in aquatic ecosystems are amplifying cyanotoxin production, threatening drinking and recreational water safety. Monitoring of these toxins is challenged by requirements of the low {micro}g/L detections limits and structural diversity. Here, we employ aerolysin nanopores to distinguish seven of the most prevalent microcystin congeners, both individually and in mixtures, at environmentally relevant concentrations. Importantly, we showed that aerolysin enables the detection of microcystins in different lake water samples at concentrations below the World Health Organizations intervention thresholds, reaching picomolar sensitivity. Moreover, combining experiments and molecular dynamics simulations, we further investigated the microcystin sensing mechanism, suggesting that the ionic current blockage is primarily governed by K238 in aerolysin, while dwell time is regulated by R220 constriction site. Our results open the way to use the nanopore sensing technology for real-time monitoring of microcystins in drinking water sources and surface waters.

bioengineering↗

bioRxiv2024

In vitro-generated inflammatory fibroblasts secrete extracellular matrix with biochemical and biophysical properties similar to tissue-remodelling fibroblasts

In solid cancers, inflammation and viral infections, two main fibroblast subtypes have been identified: myofibroblast-like fibroblasts and inflammatory fibroblasts. In the tumour microenvironment (TME), these cancer-associated fibroblast (CAF) subtypes are known as myCAFs, which generate a stiffened fibrotic extracellular matrix (ECM), and iCAFs, which secrete inflammatory cytokines to locally modulate the immune response. Yet, whether iCAFs contribute to shaping the ECM biochemical and biophysical properties remains unknown, mainly because robust in vitro models to generate fibroblast subtypes are lacking. Here, we established an in vitro cell culture system based on murine NIH3T3 fibroblasts and stimulation by TGF{beta} and IL1, alone or in combination, to induce fibroblast subtypes. Gene expression analysis of well-documented myCAF (Acta2/Tagln) and iCAF (Ccl2/Il6/Lif) markers revealed that TGF{beta} induced a myCAF-like phenotype, while a combination of TGF{beta} and IL1 induced an iCAF-like phenotype. We compared these in vitro subtypes to myCAFs and iCAFs from publicly available scRNAseq data of tumour tissues from cancer patients. We found that, similar to myCAFs, both tumour-associated and in vitro iCAFs express Acta2/Tagln as well as genes encoding for typical ECM proteins, which correlated in vitro with the ability to contract collagen. Furthermore, fluorescence microscopy and atomic force microscopy revealed that in vitro both subtypes generate thick, layered and stiff matrices with highly aligned ECM, demonstrating for the first time that iCAFs may also contribute to a pathological ECM. Finally, matrices generated from these in vitro fibroblast subtypes, but not from uninduced or IL1-only stimulated fibroblasts, enhanced the expression of the immune suppression marker Arg1 in co-cultured macrophages. Our study provides new insights in the contribution of inflammatory fibroblasts to ECM deposition and remodelling and puts forward a well-defined in vitro model to generate different fibroblast subtypes for future in-depth mechanistic studies of their roles in cancer and other pathologies.

cell biology↗

bioRxiv2024

Lithic bacterial communities: ecological aspects focusing on Tintenstrich communities

Tintenstrich communities (TC) are mainly composed by Cyanobacteria developing on the rock substrate and forming physical structures strictly connected to the rock itself. Endolithic and epilithic bacterial communities are important because they contribute to nutrients release within run-off waters flowing on the rock surface. Despite them being ubiquitous, little information about their ecology and main characteristics is available. In this paper, we characterized the bacterial communities of rock surfaces of TC in Switzerland through Illumina sequencing and investigated their bacterial community composition on two substrate types (silicious and limestone rocks) through multivariate models. Our results show that Cyanobacteria and Proteobacteria are the predominant phyla in this environment. Bacterial alpha diversity was higher on limestone than on siliceous rock, and beta diversity of siliceous rock varied with changes in rock surface structure. Here we provide novel insights into the bacterial community composition of TC, their differences from other lithic communities, and the effects of the rock substrate and structure.

microbiology↗

bioRxiv2023

E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled family members

The transmembrane E3 ligases RNF43 and ZNRF3 perform key tumour suppressor roles by inducing endocytosis of members of the Frizzled (FZD) family, the primary receptors for WNT. Loss-of-function mutations in RNF43 and ZNRF3 mediate FZD stabilisation and a WNT-hypersensitive growth state in various cancer types. Strikingly, RNF43 and ZNRF3 mutations are differentially distributed across cancer types, raising questions about their functional redundance. Here, we compare the efficacy of RNF43 and ZNRF3 of targeting different FZDs for endocytosis. We find that RNF43 preferentially downregulates FZD1/FZD5/FZD7, while ZNRF3 displays preference towards FZD6/FZD10. We show that the RNF43 transmembrane domain (TMD) is a key molecular determinant for inducing FZD5 endocytosis. Furthermore, a TMD swap between RNF43 and ZNRF3 re-directs their preference for FZD member downregulation. We conclude that RNF43 and ZNRF3 preferentially downregulate specific FZDs by a TMD-dependent mechanism. In accordance, tissue-specific expression patterns of FZD homologues correlate with the incidence of RNF43 or ZNRF3 cancer mutations in those tissues. Consequently, our data point to druggable vulnerabilities of specific FZD receptors in RNF43- or ZNRF3-mutant human cancers.

cell biology↗

bioRxiv2019

RNF43 truncating mutations mediate a tumour suppressor-to-oncogene switch to drive niche-independent self-renewal in cancer

Wnt/{beta}-catenin signalling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligase RNF43 gives rise to Wnt-hypersensitive tumours that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class of RNF43 truncating cancer mutations that strongly induce {beta}-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulating activity. Mechanistically, these RNF43 mutants trap Casein Kinase (CK)1 at the plasma membrane, which prevents {beta}-catenin turnover and propels ligand-independent Wnt target gene transcription. When introduced in human colon stem cells, these oncogenic RNF43 mutants cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Importantly, onco-RNF43 mutations, unlike conventional LOF RNF43 mutations, confer resistance to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine.

cancer biology↗

bioRxiv2018

Cytoskeletal tension actively sustains the T cell immunological synapse

When migratory T cells encounter antigen presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T cell immunity. While the cellular processes underlying synapse formation have been well-characterized, those that maintain the symmetry, and thereby the stability of the synapse remain unknown. Here we identify an antigen-triggered mechanism that actively promotes T cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott -Aldrich syndrome Protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T cell activation, WASP is degraded, leading to cytoskeletal rearrangement and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell-APC synaptic contact.

cell biology↗