SCV phenotype switch
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB25360 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Whole genome sequencing of Staphylococcus aureus strain WCH-SK2 small colony variants
| PRJNA288081 | ENA
Project description:Respiration deficient S. aureus small colony variants (SCVs) frequently cause persistent infections, which necessitates they acquire iron, yet how SCVs obtain iron remains unknown. To address this, we created a stable hemB mutant in S. aureus USA300 strain LAC. The hemB SCV utilized exogenously supplied heme but was attenuated for growth under conditions of iron starvation. RNA-seq showed that both WT S. aureus and the hemB mutant sense and respond to iron starvation.
2022-09-06 | GSE184082 | GEO
Project description:In Candida albicans the Efg1 transcription factor (a member of the APSES family) is an important regulator of hyphal growth, and of the white-to-opaque transition. In contrast, we show that the Efg1 ortholog in Candida parapsilosis is a major regulator of a different morphological switch at the colony level, from a concentric to smooth morphology. The rate of switching is at least 100-fold increased in an efg1 knockout relative to wild type. Deleting efg1 also reduces biofilm formation, and results in increased sensitivity to SDS, Congo red, caspofungin and calcofluor white in cells of both morphologies. Biofilm reduction is more dramatic in in vitro than in in vivo models. We use ChIP-seq to show that Efg1 binds to 502 promoter regions, including 70 potential transcription factors or regulatory proteins. Several of the transcription factors belong to networks that regulate biofilm development and white-opaque switching in C. albicans. Efg1 also binds to its own promoter. The binding site for C. parapsilosis Efg1 resembles that of orthologs in other fungi. Many Efg1 targets are probably also regulated by the Ndt80 transcription factor. We show that a paralog of Efg1 (Efh1) is restricted to Candida species. Efh1 does not regulate concentric-smooth phenotype switching, biofilm formation or stress response in C. parapsilosis. Our analysis supports the hypothesis that Efg1 has an ancient role as regulator of development in fungi, but we have identified a new role in C. parapsilosis as a regulator of colony switching that is distinct from the white-opaque switch in C. albicans. RNA was isolated from C. parapsilosis wild type (three biological replicates, concentric phenotype), and from efg1 deletion strains (three biological replicates from both concentric and smooth phenotype). Gene expression was determined using strand-specific RNA-seq.
2013-06-20 | E-GEOD-41064 | biostudies-arrayexpress
Project description:The non-essential amino acid serine is a critical nutrient for cancer cells due to its diverse biosynthetic functions. While some tumors can synthesize serine de novo, others are auxotrophic and therefore reliant on serine uptake. Importantly, despite several transporters being known to be capable of transporting serine, the transporter(s) that mediate serine uptake in cancer cells are not known. Here, we characterize the amino acid transporter ASCT2 (SLC1A5) as a major contributor to serine uptake in cancer cells. ASCT2 is well-known as a glutamine transporter in cancer, and our work demonstrates that serine and glutamine compete for uptake through ASCT2. We further show that ASCT2-mediated serine uptake is essential for purine nucleotide biosynthesis and that ERα promotes serine uptake by directly activating SLC1A5 transcription. Together, our work defines an additional important role for ASCT2 as a serine transporter in cancer and evaluates ASCT2 as a potential therapeutic target.
2024-06-11 | GSE269606 | GEO
Project description:In Candida albicans the Efg1 transcription factor (a member of the APSES family) is an important regulator of hyphal growth, and of the white-to-opaque transition. In contrast, we show that the Efg1 ortholog in Candida parapsilosis is a major regulator of a different morphological switch at the colony level, from a concentric to smooth morphology. The rate of switching is at least 100-fold increased in an efg1 knockout relative to wild type. Deleting efg1 also reduces biofilm formation, and results in increased sensitivity to SDS, Congo red, caspofungin and calcofluor white in cells of both morphologies. Biofilm reduction is more dramatic in in vitro than in in vivo models. We use ChIP-seq to show that Efg1 binds to 502 promoter regions, including 70 potential transcription factors or regulatory proteins. Several of the transcription factors belong to networks that regulate biofilm development and white-opaque switching in C. albicans. Efg1 also binds to its own promoter. The binding site for C. parapsilosis Efg1 resembles that of orthologs in other fungi. Many Efg1 targets are probably also regulated by the Ndt80 transcription factor. We show that a paralog of Efg1 (Efh1) is restricted to Candida species. Efh1 does not regulate concentric-smooth phenotype switching, biofilm formation or stress response in C. parapsilosis. Our analysis supports the hypothesis that Efg1 has an ancient role as regulator of development in fungi, but we have identified a new role in C. parapsilosis as a regulator of colony switching that is distinct from the white-opaque switch in C. albicans.
2013-06-20 | GSE41064 | GEO
Project description:The ATP binding cassette (ABC) transporter family is widely distributed in vertebrates and is essential for drug resistance, cell signaling and energy homeostasis. There is growing evidence that various ABC transporters contribute to the growth and development of tumors but relatively little is known about how the ABC transporter family behaves in hepatocellular carcinoma (HCC). ABCC6 transporter was downregulated in HCC tissues and that it was associated with successful treatment for HCC patients. Cellular model studies have shown that ABCC6 plays a role in the migration and cytoskeleton rearrangement of HepG2 hepatocarcinoma cells, highlighting its role in cancer biology. Abcc6-silenced HepG2 cells are used as cell model to obtain more deep information about the molecular mechanisms underlying the observed results. MTT and colony formation assays, showed the effects of Abcc6 on HepG2 cell proliferation. Western blotting analysis, real-time PCR, and immunofluorescence were used to find the E-cadherin, Vimentin, and N-cadherin markers associated with the epithelial-to-mesenchymal transition (EMT). Colony formation experiments in the current study showed that Abcc6 decreased HepG2 cell viability. The migratory and invasion activities were dramatically slowed down by Abcc6 silencing, according to the Transwell and wound-healing assays. In tumor cells, EMT has been shown to be crucial for enhancing migration and invasion and is frequently characterized by a loss of epithelial markers (E-cadherin) and an increase in mesenchymal markers (Vimentin and N-cadherin). In the western blotting examination, E-cadherin expression was considerably elevated compared to the control group, while N-cadherin and Vimentin expression were downregulated. This led to the hypothesis that the underlying mechanism of Abcc6 knockdown prevents migration and invasion in HepG2 cells and is linked to the suppression of EMT. In conclusion all evidence suggested that ABC transporters play a more active role in cancer biology.
2024-01-02 | E-MTAB-13154 | biostudies-arrayexpress
Project description:The serotonin transporter, SERT, catalyzes serotonin reuptake at the synapse to terminate neurotransmission via an alternating access mechanism, and SERT inhibitors are the most widely prescribed antidepressants. Here, deep mutagenesis is used to determine the effects of nearly all amino acid substitutions on human SERT surface expression and transport of the fluorescent substrate analogue APP+, identifying many mutations that enhance APP+ import. Comprehensive simulations of the entire ion-coupled import process reveal that while binding of the native substrate, serotonin, reduces free energy barriers between conformational states to promote SERT dynamics, the conformational free energy landscape in the presence of APP+ instead resembles Na+ bound-SERT, with a higher free energy barrier for isomerization to an inward-facing state. The deep mutational scan for SERT-catalyzed import of APP+ finds mutations that promote the necessary conformational changes that would otherwise be facilitated by the native substrate. Indeed, hundreds of gain-of-function mutations for APP+ import are found along the permeation pathway, most notably mutations that favor opening of a solvent-exposed intracellular vestibule. The mutagenesis data support the simulated mechanism in which the neurotransmitter and a symported sodium share a common cytosolic exit pathway to achieve coupling. Furthermore, the mutational landscape for SERT surface trafficking, which likely filters out misfolded sequences, reveals that residues along the permeation pathway are mutationally tolerant, providing plausible evolutionary pathways for changes in transporter properties while maintaining folded structure.
2019-07-31 | GSE109499 | GEO
Project description:Iron is a modifier of the phenotypes of JAK2-mutant myeloproliferative neoplasms
2022-08-18 | GSE184254 | GEO
Project description:ra03-04_elongation_isoxaben - time course - 1. Study the molecular basis of the growth acceleration observed in hypocotyl cells. We previously have observed that cell elongation takes place in two distinct phases (Refregier et al., 2004). A slow growth phase during which a thick polylamellated wall is deposited and a rapid growth phase during which cell wall polymers are extensively remodelled. In dark-grown hypocotyls the slow growth phase takes place during the first 48h after seed-imbibition synchronously in all cells. At 48h after imbibition, cells at the basis of the hypocotyl undergo a growth acceleration, this acceleration follows an acropetal gradient along the hypocotyl. In this experiment, we investigated the changes in transcript abundance that accompany this sudden increase in growth rate. 2. Study the feed-back mechanisms involved in the coordination between cellulose synthesis and the cell elongation. The inhibition of cellulose using chemical inhibitors also inhibits cell elongation. In the same study (Refregier et al., 2004), we have observed that the effect of the cellulose synthesis inhibitor isoxaben on cell elongation is different dependent on the growth stage. When applied during the slow growth phase, cells continue to elongate slowly and do not show the growth acceleration at 48h after imbibition. Surprisingly, when applied after the growth acceleration, isoxaben does not inhibit subsequent growth. In this study we compared the effects of isoxaben on the transcript profiles before and after the growth acceleration. This should inform us about the response of the hypocotyl cells to the inhibition of cellulose and should provide insights into the molecular events that underly the observed coupling between cellulose synthesis and cell elongation. - 1- Time course from 45h until 55h after seed-imbibition, comparisons respectively between: 45h - 48h, 48h - 52h, 52h - 55h Keywords: time course
2007-06-20 | GSE7986 | GEO
Project description:Melanoma is the deadliest of skin cancers and has a high tendency to metastasize to distant organs. Calcium and metabolic signals contribute to melanoma invasiveness; however, the underlying mo¬lecular details are elusive. The MCU complex is a major route for calcium into the mitochondrial matrix but whether MCU affects melanoma pathobiology is not understood. Here, we show that MCUA expression correlates with melanoma patient survival and is decreased in BRAF kinase inhibitor-resistant melanomas. Knockdown (KD) of MCUA suppresses melanoma cell growth and stimulates migration and invasion. In melanoma xenografts, MCUA_KD reduces tumor volumes but promotes lung metastases. Proteomic analyses and protein microarrays identify pathways that link MCUA and melanoma cell phenotype and suggest a major role for redox regulation. Antioxidants enhance melanoma cell migration, while pro-oxidants diminish the MCUA_KD-induced invasive phenotype. Furthermore, MCUA_KD increases melanoma cell resistance to immunotherapies and ferroptosis. Collectively, we demonstrate that MCUA controls melanoma aggressive behavior and therapeutic sensitivity. Manipulations of mitochondrial calcium and redox homeostasis, in combination with current therapies, should be considered in treating advanced melanoma.
| S-SCDT-EMBOR-2022-54746-T | biostudies-other