Biology subjects

Roeder, T.

Publications and source records attributed to Roeder, T..

15 recordsLinked to original sources

bioRxiv2026

Preconception e-nicotine impairs airway development and progenitor proliferation across generations in Drosophila Melanogaster

Electronic nicotine delivery devices are increasingly used worldwide, raising concern about the potential effects of nicotine exposure during fetal and early postnatal development. However, evidence regarding the effects of vaping during pregnancy remains limited, and the consequences of exposure before conception are largely unknown. Here, we investigated whether maternal nicotine vaping prior to conception alters airway development using the fruit fly Drosophila melanogaster. Offspring of nicotine-exposed mothers exhibited abnormal airway architecture, epithelial remodelling, and impaired terminal branching. These defects were accompanied by reduced proliferation of airway progenitor cells without increased apoptosis, resulting in decreased hypoxia tolerance, altered activity patterns, and reduced lifespan. Transcriptomic and functional analyses revealed suppression of innate immune signalling mediated by nuclear factor kappa-B (NF-{kappa}B). Notably, knockdown of its regulator Relish reproduced key phenotypes. Developmental abnormalities persisted across generations, with their severity progressively declining. Together, these findings identify maternal preconception nicotine exposure as a previously unrecognized determinant of airway development and provide insight into early origins of chronic airway disease. TeaserPreconception e-nicotine exposure shapes airway development, structural and physiological abnormalities across generations in Drosophila.

Developmental Biology↗

bioRxiv2025

JNK integrates immune and stress signals to balance apoptosis and proliferation in airway progenitors

Chronic inflammation disrupts epithelial regeneration, yet how immune signaling reprograms progenitor fate remains unclear. Using the Drosophila airway as a model of epithelial remodeling, we identify the c-Jun N-terminal kinase (JNK) pathway as a central integrator of immune and stress cues that balances apoptosis and compensatory proliferation in airway progenitors. Persistent activation of the innate immune IMD pathway induces simultaneous cell death and proliferation through a non-canonical route that bypasses NF-{kappa}B/Relish and instead engages JNK. Downstream, distinct transcriptional modules orchestrate these divergent fates: Foxo and AP-1 drive apoptosis, whereas the ETS factor Ets21C mediates proliferation. Genetic inhibition of JNK or its effectors restores progenitor homeostasis, while constitutive activation recapitulates inflammation-induced tissue remodeling. These responses are cell-autonomous, revealing that airway progenitors actively interpret immune and stress signals to determine their fate. Collectively, our findings uncover a modular signaling architecture that links inflammation to regeneration and highlight conserved JNK-dependent transcriptional programs as potential therapeutic targets to prevent progenitor exhaustion in chronic airway disease.

cell biology↗

bioRxiv2025

JAK/STAT Signaling Governs Airway Epithelial Homeostasis and Stress Resilience in Drosophila

Airway epithelia must maintain barrier integrity while continuously adapting to changing environmental conditions. This requires key signaling pathways in airway epithelia to operate within a tightly controlled functional range. Here, we show that airway epithelial homeostasis in Drosophila depends on balanced JAK/STAT signaling. Basal pathway activity is constitutively present in differentiated epithelial cells and is necessary for cell survival, epithelial integrity and stress resistance. In accordance with this role as a stress responsive regulator in epithelial biology, environmental stressors, including hypoxia, cigarette smoke, and cold exposure, induce JAK/STAT signaling. In contrast, sustained pathway activation is associated with airway remodeling characterized by epithelial thickening, luminal narrowing, and altered cellular organization. Transcriptomic analysis reveals that sustained activation is associated with a coordinated epithelial stress program integrating immune signaling, proteostasis, and metabolic adaptation. Cross-species comparisons with murine and human datasets suggest that key aspects of this response are conserved. Pharmacological inhibition demonstrates that remodeling depends on continued pathway activity and can be partially reversed in vivo. Together, our findings support a model in which airway epithelial homeostasis depends on maintaining JAK/STAT signaling within a defined functional range. This "Goldilocks" principle provides a conceptual framework for understanding how epithelial stress responses are balanced under physiological and pathological conditions. Graphical abstract

cell biology↗

bioRxiv2024

A marsh samphire (Salicornia europaea) extract induces a strictly sex-specific, Tor-signaling-dependent extension of lifespan and exhibits anti-obesogenic properties

We have studied the health-promoting properties of the marsh samphire Salicornia europaea by employing the fruit fly Drosophila melanogaster. Supplementing a standard diet with 0.2% of an aqueous extract of this halophilic plant (SEE), which grows in sandy and muddy habitats in intertidal zones, extended the lifespan of two different Drosophila strains by up to a third. This effect was strictly sex-specific and only affected females. When analyzing the body composition, we found that the body fat content of SEE-treated female flies was lower compared to controls. The extract also positively impacted the lifespan of flies fed a high-fat diet but not a high-sugar diet. It is of note in this context that SEE exhibited a lipase-inhibitory activity in vitro. Moreover, SEE counteracted ageing-associated loss of intestinal barrier integrity. The sex-specific lifespan extensions induced by the SEE were entirely dependent on functional Tor signaling in the flies. Tissue-specific silencing of the Tor signalling pathway in different cellular compartments of the intestine reduced, but did not completely abolish, the lifespan-prolonging effect in females. This suggests that other organs also contribute to this effect. In contrast to the observation that Tor signalling is necessary for the life-prolonging effect, Foxo deficiency led to a reduction in the effect, but not to its complete absence. In conclusion, the SEE is a promising candidate for a health-promoting intervention, and we laid the current groundwork for identifying the compounds that mediate this effect in future studies.

physiology↗

bioRxiv2024

Terminal tracheal cells of Drosophila are immune privileged to maintain their Foxo-dependent structural plasticity

Respiratory organs must balance their primary function of gas exchange with the constant threat of inhaled pathogens. In the Drosophila tracheal system, gas exchange occurs at the tracheal terminal cells (TTCs), the functional equivalents of mammalian alveoli. While bacterial infection triggers a robust innate immune response throughout the broader airway epithelium, we reveal that TTCs are uniquely exempt from this reaction. Mechanistically, TTCs lack expression of the membrane-associated peptidoglycan recognition receptor PGRP-LC. This absence protects these highly susceptible cells from Immune deficiency (Imd) pathway activation and subsequent JNK-mediated cell death, establishing TTCs as a distinct, immune-privileged niche. Ectopic immune activation via targeted PGRP-LCx overexpression in TTCs caused a severe reduction in branching, cellular damage, and ultimately cell death, phenotypes that were fully rescued by the depletion of AP-1 or foxo. Because both structural plasticity (in response to nutritional cues and hypoxia) and innate immune responses strictly require the transcription factor FoxO, we demonstrate that potent immune signaling is fundamentally incompatible with dynamic TTC remodeling. Ultimately, the immune-privileged status of TTCs represents an essential evolutionary trade-off, restricting local inflammation to preserve foxo-dependent structural plasticity and vital respiratory function.

immunology↗

bioRxiv2024

Cytoadhesion of Plasmodium falciparum-infected red blood cells changes the expression of cytokine-, histone- and antiviral protein-encoding genes in brain endothelial cells

Malaria remains a significant global health problem, mainly due to Plasmodium falciparum, which is responsible for most fatal infections. Infected red blood cells (iRBCs) evade spleen clearance by adhering to endothelial cells (ECs), triggering capillary blockage, inflammation, endothelial dysfunction and altered vascular permeability, prompting an endothelial transcriptional response. The iRBCIT4var04/HBEC-5i model, where iRBCs present IT4var04 (VAR2CSA) on their surface, was used to analyse the effects of iRBC binding on ECs at different temperature (37{degrees}C vs. 40{degrees}C). Binding of non-infected RBCs (niRBCs) and fever alone altered the expression of hundreds of genes in ECs. Comparing the expression profile of HBEC-5i cells cultured either in the presence of iRBCs or in the presence of niRBCs revealed significant upregulation of genes linked to immune response, nucleosome assembly, NF-kappa B signaling, angiogenesis, and antiviral immune response/interferon-alpha/beta signaling. Raising the temperature to 40{degrees}C, simulating fever, led to further upregulation of many genes, particularly those involved in cytokine production and angiogenesis. In summary, the presence of iRBCs stimulates ECs, activating several immunological pathways and affecting antiviral (- parasitic) mechanisms and angiogenesis. Our data uncovered the induction of the interferon-alpha/beta signaling pathway in ECs in response to iRBCs.

microbiology↗

bioRxiv2024

FoxO factors are essential for maintaining organ homeostasis by acting as stress sensors in airway epithelial cells

Airway epithelia must maintain functional and structural homeostasis despite exposure to diverse environmental stressors. FoxO transcription factors are well suited to this task, acting as integration hubs that translate extrinsic and intrinsic signals into appropriate physiological responses. We show that FoxO factors in Drosophila, mouse, and human airway epithelial cells (AECs) undergo nuclear translocation in response to stressors including hypoxia, temperature, and oxidative stress. In human airway epithelial cell lines, individual hFOXO factors show distinct, cell-type-specific activation patterns. In Drosophila, hypoxia was the only stressor among those tested that triggered a dfoxo-dependent innate immune response. Because Drosophila possesses a single FoxO ortholog, loss-of-function analysis directly demonstrated that dfoxo is required for stress resistance in the airway epithelium. Reduced FoxO expression was similarly observed in mouse models of asthma and in airway samples from asthma patients, paralleling the increased stress sensitivity seen upon FoxO loss in flies. While our data do not establish that reduced FOXO levels cause asthma, they indicate that FoxO-dependent stress pathways are altered in diseased airways across species. Together, these findings support a model in which FoxO coordinates adaptive epithelial stress responses that maintain airway homeostasis under environmental challenge.

physiology↗

bioRxiv2023

Proteins differentially expressed between pathogenic and non-pathogenic Entamoeba histolytica clones influence pathogenicity by different mechanisms

Recently, two genes involved in pathogenicity in a mouse model of amoebic liver abscess were identified based on their differential expression between non-pathogenic (A1np) and pathogenic (B2p) clones of the Entamoeba histolytica isolate HM:1-IMSS. While overexpression of a gene encoding the metallopeptidase EhMP8-2 decreases the virulence of the pathogenic clone B2p, overexpression of the gene ehi_127670 (ehhp127), encoding a hypothetical protein, increases the virulence of the non-pathogenic clone A1np, while silencing this gene in B2p decreases virulence. To understand the role of both molecules in determining the pathogenicity of E. histolytica, silencing and overexpression transfectants were characterized in detail. Silencing of ehmp8-2, of the homologous gene ehmp8-1, or of both together in A1np trophozoites significantly altered the transcript levels of 60-350 genes. This strong change in the expression profile caused by the silencing of ehmp8-1 and/or ehmp8-2 implies that these peptidases regulate expression of numerous genes. Consequently, numerous phenotypic characteristics including cytopathic, hemolytic and cysteine peptidase activity were changed in response to their silencing. Silencing of ehhp127 in B2p trophozoites did not affect other genes, whereas overexpression in A1np trophozoites results in an altered expression of approximately 140 genes. EhHP127 appears to be important for trophozoite movement, as silencing negatively affects and overexpression positively affects trophozoite motility. Interestingly, the specific silencing of ehhp127 also impairs cytopathic activity, cysteine peptidase and hemolytic activity. All three molecules of interest, namely EhMP8-1, EhMP8-2, and EhHP127 can be detected in amoeba vesicles. Our results clearly show that the proteins studied here influence the pathogenicity of amoebae in different ways and use entirely different mechanisms to do so. Author summaryThe human pathogen Entamoeba histolytica can live asymptomatically in the intestine or become invasive and cause fatal liver abscesses. Approximately 15,000 people die each year as a result of an amoebic infection. Recently, two clones with different pathogenicity (A1np: non-pathogenic; B2p: pathogenic) derived from the E. histolytica isolate HM:1-IMSS were compared at the transcriptome level. Two highly differentially expressed genes (ehhp127 encoding a hypothetical protein and ehmp8-2 encoding a metallopeptidase) were identified. Analysis of E. histolytica transfectants showed that silencing of ehhp127 and overexpression of ehmp8-2 in B2p trophozoites reduced amoebic liver abscess formation in the mouse model. In this study, we characterized E. histolytica silencing and overexpression transfectants of ehmp8-2, as well as of the homologous gene ehmp8-1 and of ehhp127. It was shown that the altered expression of the metallopeptidase genes has a strong influence on the expression of a large number of genes and that the phenotype is strongly altered as a result. Silencing of ehhp127 does not affect the overall expression profile. However, specific silencing has a negative effect on motility, cysteine peptidase, hemolytic and cytopathic activity. All three molecules were shown to be localized in trophozoite vesicles.

cell biology↗

bioRxiv2023

A mitochondrial sirtuin shapes the intestinal microbiota by controlling lysozyme expression

Sirtuins act as cellular sensors in the gut that control a substantial change in gut properties in response to environmental changes. Here we show that the only mitochondrial sirtuin of Drosophila, dSirt4, is strongly up-regulated by a protein-reduced diet. Flies with a dSirt4 defect show strong changes in the protein pattern and physiological properties of their intestine. One of the most notable effects was the strong induction of lysozyme gene expression in the intestine, which also translates into enhanced lysozyme activity. This effect was cell autonomous, as it was also observed in flies with dsirt4 was exclusively silenced in enterocytes of the intestine. Although this strongly increased lysozyme expression, it did not reduce total bacterial load in the intestine, but rather changed the composition of the microbiota by reducing the number of gram-positive bacteria. This effect on microbiota composition can be attributed to the dSirt4-dependent lysozyme expression, as it was absent in a lysozyme-deficient background. dSirt4 deficiency in enterocytes reduced lifespan of flies, which was also observed in those flies experiencing ectopic lysozyme overexpression in enterocytes. This implies that strong lysozyme expression leads to a dysbiotic state associated with reduced lifespan.

cell biology↗

bioRxiv2023

Recurrent phases of strict protein limitation inhibit tumor growth and restore lifespan in a Drosophila intestinal cancer model

Diets that restrict caloric or protein intake offer a variety of benefits, including decreasing the incidence of cancer. However, whether such diets pose a substantial therapeutic benefit as auxiliary cancer treatments remains unclear. We determined the effects of severe protein depletion on tumorigenesis in a Drosophila melanogaster intestinal tumor model, using a human RAF gain-of-function allele. Severe and continuous protein restriction significantly reduced tumor growth but resulted in premature death. Therefore, we developed a diet in which short periods of severe protein restriction alternated cyclically with periods of complete feeding. This nutritional regime reduced tumor mass, restored gut functionality, and normalized the lifespan of oncogene-expressing flies to the levels observed in healthy control flies. Furthermore, this diet reduced the chemotherapy-induced stem cell activity associated with tumor recurrence. Transcriptome analysis revealed long-lasting changes in the expression of key genes involved in multiple major developmental signaling pathways. Overall, the data suggest that recurrent severe protein depletion effectively mimics the health benefits of continuous protein restriction, without undesired nutritional shortcomings. This provides seminal insights into the mechanisms of the transcriptomic memory effect required to maintain the positive effects of protein restriction throughout the phases of a full diet.

cancer biology↗

bioRxiv2020

Monoterpenes alter TAR1-driven physiology in Drosophila species

Monoterpenes are molecules with insecticide properties whose mechanism of action is however not completely elucidated. Furthermore, they seem to be able to modulate the monoaminergic system and several behavioural aspects in insects. In particular, tyramine (TA) and octopamine (OA) and their associated receptors orchestrate physiological processes such as feeding, locomotion and metabolism. Here we show that monoterpenes not only act as biopesticides in Drosophila species but can cause complex behavioural alterations that require a functional type 1 tyramine receptors (TAR1s). Variations in metabolic traits as well as locomotory activity were evaluated in both Drosophila suzukii and Drosophila melanogaster after treatment with three monoterpenes. A TAR1-/- D. melanogaster strain was used to better understand the relationships between the receptor and monoterpenes-related behavioural changes. Immunohistochemistry analysis revealed that, in the D. melanogaster brain, TAR1 appeared to be expressed in areas controlling metabolism. In comparison to the D. melanogaster wild type, the TAR-/- flies showed a phenotype characterized by higher triglyceride levels and food intake as well as lower locomotory activity. The monoterpenes, tested at sublethal concentrations, were able to induce a downregulation of the TAR1 coding gene in both Drosophila species. Furthermore, monoterpenes also altered the behaviour in D. suzukii and D. melanogaster wild types 24 h after a continuous monoterpene exposure. Interestingly, they were ineffective in modifying the physiological performances of TAR1-/- flies. In conclusion, it appears that monoterpenes not only act as biopesticides for Drosophila but they can also interfere with its behaviour and metabolism in a TAR1-dependent fashion.

animal behavior and cognition↗

bioRxiv2020

Balanced JAK/STAT signaling is critical to maintain the functional and structural integrity of the Drosophila respiratory epithelium

Signaling mediated by the Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is critical for maintaining cellular and functional homeostasis in the lung. Thus, chronically activated JAK/STAT signaling is causally associated with lung diseases such as lung cancer, asthma, and chronic obstructive pulmonary disease. To elucidate the molecular processes that transform increased JAK/STAT signaling in airway epithelial cells into the known pathological states, we used a highly simplified model system, the fruit fly Drosophila melanogaster. Here, the JAK/STAT pathway is permanently active in almost all airway cells and responds to airborne stressors with increased activity. Silencing of this signaling pathway in epithelial cells resulted in apoptosis. Since the above-mentioned lung diseases are commonly associated with increased JAK/STAT signaling, we assessed this by its ectopic activation in the respiratory epithelium of Drosophila. This intervention triggered cell-autonomous structural changes in epithelial cells. These structural changes included phenotypes associated with asthma, namely, thickening of the epithelium, substantial narrowing of the air-conducting space, and impairment of the secretory epicuticular structure of the tracheae. Pharmacological manipulation of JAK/STAT signaling reversed this pathological phenotype. Transcriptomic analyses revealed that several biological processes were affected, which is consistent with the impairment of junction protein trafficking also observed in this study. These results indicate that balanced JAK/STAT signaling is essential for the functionality of the respiratory epithelium and, by extension, the entire organ. In contrast, chronic overactivation of this signaling leads to massive structural changes that are closely associated with pathologies typical of chronic inflammatory lung diseases. HighlightsO_LIJAK/STAT signaling is active in the entire Drosophila respiratory system in all developmental stages. C_LIO_LIThe signaling pathway is indispensable for the survival of the tracheal cell. C_LIO_LIOveractivation of the signaling has significant effects on tracheal development and also displays a human disease-associated phenotype in Drosophila trachea. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/160929v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1f82913org.highwire.dtl.DTLVardef@150a79corg.highwire.dtl.DTLVardef@2c1130org.highwire.dtl.DTLVardef@11c7cf8_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Phytochrome mediated responses in Agrobacterium fabrum: growth, swimming, plant infection and interbacterial competition

The soil bacterium Agrobacterium fabrum C58 infects plants by a unique DNA transfer mechanism. A. fabrum has two phytochrome photoreceptors, Agp1 and Agp2. We found that DNA transfer into plants by A. fabrum is down regulated by light and that phytochrome knockout mutants have diminished DNA transfer rates. The regulation pattern matches with that of bacterial conjugation reported earlier. Growth, swimming and interbacterial competition were also affected in phytochrome knockout mutants, although these effects were often not affected by light. We can thus distinguish between light-regulated and light-independent phytochrome responses. In microarray studies, transcription of only 4 genes was affected by light, indicating that most light responses are regulated post-transcriptionally. In a mass spectrometery-based proteomic study, 24 proteins were different between light and dark grown bacteria, whereas 382 proteins differed between wild type and phytochrome knockout mutants, pointing again to light-dependent and light-independent roles of Agp1 and Agp2.

microbiology↗

bioRxiv2019

bioRxiv: the preprint server for biology

The traditional publication process delays dissemination of new research, often by months, sometimes by years. Preprint servers decouple dissemination of research papers from their evaluation and certification by journals, allowing researchers to share work immediately, receive feedback from a much larger audience, and provide evidence of productivity long before formal publication. Launched in 2013 as a non-profit community service, the bioRxiv server brought preprinting to the life sciences and recently posted its 310,000th manuscript. The server now receives around ten million views per month and hosts papers spanning all areas of biology. Initially dominated by evolutionary biology, genetics/genomics and computational biology, bioRxiv has been increasingly populated by papers in neuroscience, cell and developmental biology, and many other fields. bioRxiv and its sister server, medRxiv, also played a critical role during the pandemic, rapidly disseminating new discoveries in immunology, virology and epidemiology related to the SARS-CoV-2 virus and its effects. Changes in journal and funder policies that encourage preprint posting helped drive adoption, as did the development of bioRxiv technologies that allow authors to transfer papers easily between bioRxiv and journals. A recent user survey found that 30% of authors post their preprints weeks to months before submitting to a journal whereas 55% post around the time of journal submission. Authors are motivated by a desire to share work early; they value the feedback they receive and very rarely experience any negative consequences of preprint posting. Rapid dissemination via bioRxiv is also encouraging new initiatives that experiment with the peer review process and the development of novel approaches to literature filtering and assessment.

scientific communication and education↗

bioRxiv2019

High fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine

Over-consumption of high-fat diets (HFDs) is associated with several pathologies. Although the intestine is the organ that comes into direct contact with all diet components, the impact of HFD has mostly been studied in organs that are linked to obesity and obesity related disorders. We used Drosophila as a simple model to disentangle the effects of a HFD on the intestinal structure and physiology from the plethora of other effects caused by this nutritional intervention. Here, we show that a HFD triggers activation of intestinal stem cells in the Drosophila midgut. This stem cell activation was transient and preceded by induction of JNK signaling in enterocytes. JNK (basket) within enterocytes was essential for activation of stem cells in response to a HFD. Moreover, this nutritional intervention leads to upregulation of the cytokine upd3 in enterocytes, a reaction that is known to trigger STAT signaling in intestinal stem cells followed by their activation. We also showed that the indigenous microbiota was essential for HFD-induced stem cell activation because this response was blunted in germ-free flies lacking a microbiota. Moreover, chronic HFD feeding of flies markedly altered both the microbiota composition and bacterial load. Although HFD-induced stem cell activity was transient, long-lasting changes to the cellular composition, including a substantial increase in the number of enteroendocrine cells, were observed. Taken together, a HFD enhances stem cell activity in the Drosophila gut and this effect is completely reliant on the indigenous microbiota and also dependent on JNK signaling within intestinal enterocytes.\n\nAuthor summaryHigh-fat diets have been associated with a plethora of morbidities. The major research focus has been on its effects on obesity related disorders, mostly omitting the intestine, although it is the organ that makes the first contact with all diet components. Here, we aimed to understand the direct effects of HFD on the intestine itself. Using Drosophila as a model, we showed that HFD induced a transient activation of intestinal stem cells. This response completely depended on JNK signaling in enterocytes. Mechanistically, we found that HFD induces JNK signaling in enterocytes, which triggers production of the cytokine upd3. This, in turn activates STAT signaling in intestinal stem cells, leading to their activation. Surprisingly, we found that a HFD triggered induced stem cell activation critically depends on the indigenous microbiota, as in germ free flies this reaction was completely abolished. Moreover, HFD changed both, composition and abundance of the microbiota. As fecal transfer experiments failed to recapitulate the HFD phenotype, we assume that the increased bacterial load is the major cause for the HFD triggered stem cell activation in the intestine.

physiology↗