Biology Open最新文献

{"title":"Shifting paradigms: phosphatases from basic biology to druggable targets.","authors":"Catia L Pierotti, Marian Brenner, Yamini Chand, Fabrice Krier, Melina Lappe, Franziska Schedel, Malgorzata Trebacz","doi":"10.1242/bio.062400","DOIUrl":"https://doi.org/10.1242/bio.062400","url":null,"abstract":"<p><p>The EMBO Workshop 'Phosphatases: from basic research to translation' (27 to 31 July 2025, Würzburg, Germany) brought together researchers from academia and industry for a deep dive into the rapidly evolving world of phosphatase biology. Over five days, participants explored the interplay of phosphatase structure, function, regulation, and signalling, while also uncovering their expanding influence in cancer, immunology, neurological disorders, and cardiometabolic health. The central focus of the meeting was the accelerating progress in phosphatase drug discovery, an enzyme class historically considered undruggable. This Meeting Review summarises the key findings and novel insights presented at the meeting and reflects the progress being made in the field.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncoupling of nutrient sensing and cell size control by specific defects in ceramide structure.","authors":"José Ignacio Quesada-Márquez, Ana Serrano, María Alcaide-Gavilán, Rafael Lucena","doi":"10.1242/bio.062633","DOIUrl":"https://doi.org/10.1242/bio.062633","url":null,"abstract":"<p><p>Ceramides are essential structural lipids whose chemical diversity arises from variations in acyl-chain length and sphingoid-base modifications, yet how these structural features couple metabolic state to growth regulation remains unclear. In Saccharomyces cerevisiae, the TORC2-Ypk1/2 signaling axis coordinates plasma membrane homeostasis with cellular growth; however, the lipid-derived signals modulating this pathway are not fully defined. Here, we establish that the elongation of very-long-chain fatty acids (VLCFAs) specifically to C26 is a critical determinant of the nutrient-dependent regulation of TORC2 activity. Based on a molecular caliper model for acyl-chain determination, we show that the TORC2-Ypk1 axis is specifically tuned to detect the successful completion of C26-VLCFA synthesis. Disrupting VLCFA elongation (elo3▵) triggers constitutive TORC2 hyperactivation and a failure to reduce cell size in response to nutrient limitation. By expressing mammalian ceramide synthases (CerS1-S4), we demonstrate that TORC2 nutrient-sensing is specifically tuned to acyl-chain length. While CerS1, CerS3, and CerS4 restore the rapid, nutrient-induced downregulation of TORC2, CerS2 expression phenocopies the elo3▵ mutant, exhibiting a total kinetic failure to inhibit TORC2 signaling upon nutrient shift. Notably, cells producing C18 ceramides (GhLag1) maintained size control despite elevated TORC2 activity, revealing that ceramide-dependent signaling intensity and the physical execution of size regulation can be uncoupled. We further demonstrate that while sphingoid-base hydroxylation is required for the execution of size remodeling, it is dispensable for nutrient sensing; sur2▵ mutants exhibited severe size defects despite maintaining statistically normal, nutrient-responsive TORC2 signaling. Overall, our findings reveal a functional hierarchy where the protein-mediated caliper measurement of VLCFA length serves as the primary sensor for TORC2 nutrient-responsiveness, while subsequent lipid modifications govern the biophysical execution of cell size control.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live-cell tracking of biliverdin trafficking reveals metabolic exchange between plastids and peroxisomes.","authors":"Mone Shibata, Keiji Yoshida, Hitomi Takahashi, Yutaka Kodama","doi":"10.1242/bio.062435","DOIUrl":"https://doi.org/10.1242/bio.062435","url":null,"abstract":"<p><p>Metabolite trafficking between organelles is widespread, yet many trafficking routes remain poorly understood. Biliverdin (BV), a tetrapyrrolic pigment, is involved in redox and light signaling in animal and plant cells. To visualize the inter-organelle trafficking of BV in living cells, we used smURFP, a BV-induced far-red fluorescent protein typically used for deep-tissue imaging in animals. Upon targeting of smURFP to various organelles in plant cells, we detected fluorescence from BV-bound smURFP in plastids and peroxisomes. Enhanced BV biosynthesis in plastids led to greater smURFP fluorescence in peroxisomes, and vice versa, indicating bidirectional trafficking of BV between these organelles. We also observed trafficking of BV between the cytosol and both plastids and peroxisomes, suggesting that bidirectional trafficking of BV between plastids and peroxisomes occurs via the cytosol. These findings provide a dynamic model for organelle-level metabolite trafficking.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low oxygen environment alters transcripts related to energy metabolism without altering the pluripotency core of bovine embryonic stem cells.","authors":"R Botigelli, R Braz Arcanjo, C Guiltinan, A J Morton, J M Smith, A C Denicol","doi":"10.1242/bio.062352","DOIUrl":"https://doi.org/10.1242/bio.062352","url":null,"abstract":"<p><p>Stem cell pluripotency is shaped by culture microenvironment. Growth factors, cytokines, and oxygen tension are key regulators of self-renewal and pluripotency state. Here we evaluated the adaptation of bovine embryonic stem cells (bESC) derived on mouse embryonic fibroblasts (MEF) to feeder-free conditions and the effects of low oxygen (5% O2) on their molecular profile. Primed bESC established on MEF and 21% O2 (high oxygen) were adapted to 5% O2 (low oxygen) and to feeder-free conditions in vitronectin to generate four culture conditions: high and low O2 tension in MEF and feeder-free. Adaptation to feeder-free upregulated transcripts related to cell differentiation in bESC cultured in high compared to low oxygen. Transition of bESC on MEF from normoxia to 5% O2 did not alter cell morphology or growth. Interestingly, colony morphology was maintained when transitioning bESC from MEF into feeder-free in low oxygen. Furthermore, there were fewer transcriptomic changes in bESC grown on MEF compared to feeder-free in low compared to high oxygen. While low oxygen tension did not alter the pluripotency profile of bESC, it promoted transcriptional changes related to energetic metabolism and increased mitochondrial membrane potential. These findings emphasize the importance of oxygen tension for derivation, maintenance, and performance of ESC.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation, validation, and long-term culture of mouse ear fibroblasts.","authors":"Katie L Barnes, Nicole M Davis, Billy J Erazo, Katie M Cataldo, Emmaly H Bertges, Laura J Knoll","doi":"10.1242/bio.062483","DOIUrl":"https://doi.org/10.1242/bio.062483","url":null,"abstract":"<p><p>Primary fibroblasts are essential cell culture models for studying cellular homeostasis, disease mechanisms, and host-pathogen interactions. Primary cells offer physiological relevance that immortalized cell lines cannot recapitulate. However, existing protocols for isolating and culturing primary fibroblasts lack standardization for long-term applications. Contamination by alternate cell types, variable media formulations, and poorly monitored passage numbers remain critical challenges for reproducibility. Here, we present a streamlined, cost-optimized protocol for isolating and culturing mouse ear fibroblasts (MEarFs) suitable for extended passages. We demonstrate that enriched media (Advanced DMEM F/12+15%FBS) consistently promoted adipocyte-like cell contamination in long-term MEarF cultures. In contrast, minimal media (DMEM+10% FBS) proved sufficient for both isolation and long-term culture, with fibroblast gene expression confirmed through passage 9. Cells displayed characteristic fibroblast morphology, expressed the mesenchymal marker vimentin, and maintained fibroblast-associated transcripts with minimal epithelial and adipocyte marker expression throughout culture. Bulk RNA sequencing revealed 17% of mapped genes exhibited differential abundance between passage 3 and passage 9, with enrichment in functional categories related to cell cycle regulation and paracrine signaling. This protocol provides an accessible primary fibroblast cell culture model with broad research applications emphasizing reproducibility and resource- conscious practices.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoids intrinsically redirect naïve CD4+ T cells to the bone marrow for preservation in malnourished mice.","authors":"Madeline L Smith, Jacob Hanes, Takesha R Foster, Clay Phillips, Kwesi A Dadzie, Melanie R Gubbels Bupp","doi":"10.1242/bio.062485","DOIUrl":"https://doi.org/10.1242/bio.062485","url":null,"abstract":"<p><p>Malnutrition impairs immunity and contributes significantly to child mortality. Among other immune changes during malnutrition, effector T cells experience a decline in number and function. As little is known about the effect of malnutrition on naïve T cells, we examined the impact of malnutrition on the naïve T cell population. During malnutrition, the number of naïve T cells decreased in the lymph nodes and increased in the bone marrow where naïve CD4+ T cells experienced less apoptosis than controls. An adoptive transfer experiment revealed that malnourished naïve CD4+ T cells preferentially migrated to the bone marrow, while ad libitum control cells preferentially migrated to the lymph nodes in a T cell-intrinsic fashion. Additionally, T cell-specific lack of the glucocorticoid receptor greatly reduced the number of naïve T cells in the bone marrow of malnourished mice, while dexamethasone treatment elevated the number of naïve CD4+ T cells in the bone marrow. T cell sensitivity to glucocorticoids was required for elevated expression of CXCR4 and CCR7 in naïve CD4+ T cells during malnutrition. Overall, naïve CD4+ T cell migration to the bone marrow during malnutrition is intrinsic, requires sensitivity to glucocorticoids, and likely contributes to naïve T cell preservation in mice.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Separating the generational effects of temperature and viscosity on the body size of a freshwater Mesocyclops copepod.","authors":"Zachary Wagner, Griffin Wagner, David M Fields, Jeannette Yen","doi":"10.1242/bio.062549","DOIUrl":"https://doi.org/10.1242/bio.062549","url":null,"abstract":"<p><p>Copepods are small crustacean zooplankton that closely follow Bergmann's rule, which states that larger organisms will be found at higher latitudes. While thermally driven metabolic effects and food availability are often stated to be the major driver behind this trend, temperature affects multiple variables within the copepod and its environment, one key variable to copepod ecology being viscosity. To test the effects of viscosity on copepod body size, two lineages of subtropical, freshwater Mesocyclops sp. copepods were grown for five generations in cultures of differing temperatures, 30°C and 18°C, and viscosities, natural and altered to mimic 18°C while at 30°C. Copepods grown at 30°C were on average 13.20% smaller than those grown at 18°C, regardless of viscosity. Copepods grown in 30°C cultures with the viscosity of 18°C had no body size differences when compared to copepods grown at 30°C and natural viscosity. Copepods reached sexual maturity after 10 days while grown at 30°C, and 13 days while grown at 18°C, with viscosity playing no role in maturation time. As such, this study provides further support for temperature driving copepod body size, with the viscosity of the environment playing no discernible role in the body size of these small organisms.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An ARVC-5 Drosophila knock-in model reveals new functions of Tmem43 in lipid homeostasis.","authors":"Kai Jürgens, Lena Menzel, Nora Klinke, Lisa Schäper, Sandra Ratnavadivel, Stefan Walter, Hendrik Milting, Heiko Meyer, Achim Paululat","doi":"10.1242/bio.062326","DOIUrl":"10.1242/bio.062326","url":null,"abstract":"<p><p>Arrhythmogenic right ventricular cardiomyopathy type 5 is caused by the missense mutation S358L in the gene TMEM43 in humans. To date, the molecular mechanisms underlying the disease remain poorly understood. We established a CRISPR/Cas9 knock-in Drosophila model carrying the orthologous Tmem43p.S333L mutation to investigate these mechanisms in vivo. The resulting flies were viable but displayed reduced lifespan, smaller body size, lipid droplet accumulation, and mitochondrial defects. Proteomic and lipidomic profiling revealed a dosage-dependent misregulation of the energy metabolism, concomitant with reduced fatty acid synthesis and ß-oxidation rates, altered peroxisomal pathways, and changes in membrane phospholipid composition. Notably, phosphatidylethanolamine (PE) and phosphatidylinositol (PI) levels were elevated, while triacylglycerols were reduced. Ultrastructural analyses confirmed mitochondrial degradation in the muscle tissue of corresponding mutants. These findings establish Tmem43p.S333L knock-in flies as a robust in vivo model of ARVC-5 and support a role for TMEM43 in linking lipid homeostasis to mitochondrial energy metabolism and integrity. Mutation-derived impairments in these processes result in cardiomyopathy.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonsense mutations can increase mRNA levels.","authors":"Precious O Owuamalam, Md Nazmul Hossain, Saverio Brogna","doi":"10.1242/bio.062444","DOIUrl":"10.1242/bio.062444","url":null,"abstract":"<p><p>Nonsense mutations can reduce mRNA levels, as premature translation termination may lead to the activation of nonsense-mediated mRNA decay (NMD). To examine how positional context influences these outcomes, we introduced premature translation termination codons (PTCs) at 15 locations within the coding region of a GFP reporter gene in Schizosaccharomyces pombe. PTCs in the first third of the coding region consistently led to reduced mRNA levels. In contrast, most downstream PTCs showed modest or minimal reductions, and several were associated with increased mRNA levels relative to the PTC-less control transcript. Measurement of transcript stability for one such variant indicated that the increased abundance was not attributable to decreased turnover. UPF1 deletion in wild-type cells elevated the levels of transcripts that were reduced and, unexpectedly, further increased transcripts' abundance to exceed the control level. In spliced versions of these constructs, downstream PTCs generally reduced mRNA levels regardless of exon junction position. Overall, these observations indicate that an unexpected consequence of nonsense mutations can be increased mRNA levels. These findings may aid in the interpretation of the effects of nonsense mutations on mRNA abundance beyond the predictions of current NMD models and may also help in the design of eukaryotic gene expression constructs.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drak is a potential binding partner of Drosophila Filamin.","authors":"Riku O Korkiamäki, Chandan Thapa, Hannah J Green, Jari Ylänne","doi":"10.1242/bio.062185","DOIUrl":"10.1242/bio.062185","url":null,"abstract":"<p><p>Mechanosensing involves proteins detecting mechanical changes in the cytoskeleton or at cell adhesion sites. These interactions initiate signaling cascades that produce biochemical effects such as post-translational modifications or cytoskeletal rearrangements. Filamin is a ubiquitous mechanosensing protein that binds actin filaments and senses pulling forces within the cytoskeleton. Drosophila Filamin (Cheerio) is structurally similar to mammalian Filamin, with roles in egg chamber development, embryo cellularization, and integrity of muscle attachment sites and Z discs in Drosophila indirect flight muscles (IFMs). Here, we report a potential novel binding partner of Drosophila Filamins: the death-associated protein kinase Drak that functions as a myosin light chain kinase. We found that Drak biochemically bound to an open mutant of Filamin that resembles the mechanically activated form, partially bound to wild-type Filamin, and did not bind to closed mutant of Filamin. The interaction site was mapped to the intrinsically unfolded C-terminal region of Drak. To study the functional role of Drak-Filamin interaction, we studied two developmental events in which Drak has been earlier shown to be expressed and in which Filamin also functions: early embryonic cellularization and indirect flight muscle development at pupal stages. We found partial colocalization between Drak-GFP and Filamin-mCherry during the initiation of cellularization furrow and at the time of myotube attachment site maturation in tendon cells. However, functionally, we could not show direct correlation between Filamin and Drak. Our studies reveal interesting new expression patterns of Drak during Drosophila development and provide detailed information about Filamin localization during IFM development.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}