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Effects of inhibiting sphingolipid synthesis and TOR signaling on the Candida albicans transcriptome

ABSTRACT: Effects of inhibiting sphingolipid synthesis and TOR signaling on the Candida albicans transcriptome

PROVIDER: PRJNA515877 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8455590.fastq.gz	Fastqsanger.gz
	SRR8455581.fastq.gz	Fastqsanger.gz
	SRR8455591.fastq.gz	Fastqsanger.gz
	SRR8455582.fastq.gz	Fastqsanger.gz
	SRR8455592.fastq.gz	Fastqsanger.gz

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Effects of inhibiting sphingolipid synthesis and TOR signaling on the Candida albicans transcriptome

Project description:Goal: We employed RNA-seq to detect changes in the transcriptome of the yeast Candida albicans in response to the addition of myriocin, a sphingolipid synthesis inhibitor, or caffeine, a drug that blocks the TOR kinase. The effects of the drugs were studied in wild-type cells and in the rtg3 mutant strain.

2019-04-01 | GSE125332 | GEO

Inhibiting sphingolipid synthesis improves outcomes and survival in GARP-mutant wobbler mouse, an ALS model

Project description:Defects of the endosomal and lysosomal systems have been increasingly linked to adult neurodegenerative diseases1,2. Deficiencies in the retrograde trafficking pathway between endosomes and the Golgi apparatus lead to forms of Alzheimer’s and Parkinson’s diseases in the case of retromer mutations, or to the rare progressive cerebello-cerebral atrophy type 2 (PCCA2) for mutations of the Golgi-associated retrograde protein (GARP) complex3. Mutations in GARP subunits lead to abnormal cellular lipid metabolism, with accumulation of sterol esters and sphingoid bases, and concomitant lysosomal dysfunction in yeast, murine, or human cells4,5. However, whether these lipid changes cause neurodegeneration and if so, which lipids are toxic, is unknown. Here, we show that GARP defects lead to global changes of cellular protein distribution, including missorting of numerous disease-linked enzymes of sphingolipid metabolism, and to the accumulation of sphingolipid intermediates in wobbler fibroblasts. Inhibiting sphingolipid synthesis in wobbler mice, a murine model of GARP deficiency with features of amyotrophic lateral sclerosis (ALS), improved wellness scores and grip strength, and increased lifespan. Our findings indicate that regulation of sphingolipids by the GARP complex is essential for neuronal health and suggest that inhibition of sphingolipid synthesis might provide a therapeutic strategy for treatment of neurodegenerative diseases due to defects in retrograde endosome-to-Golgi membrane trafficking.

2022-02-15 | PXD007981 | Pride

Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis

Project description:Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis

| PRJNA781263 | ENA

Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis

Project description:We report the application of bulk RNA sequencing to RNA extracted from lung tissue and magnetic bead isolated EpCAM+ lung epithelial cells and CD45+ lung immune cells from mice. Heterozygous serine palmitory transferase subunit 2 , Sptlc2+/- (SPT) and Sptlc2+/+ controls (WT) mice were included. Differential gene expression analysis reveals genes within the sphingolipid synthesis pathway are similarly expressed in the lung and lung epithelial cells of RV infected WT mice and SPT mice (both infected and uninfected).

2021-11-20 | GSE189056 | GEO

Identification of a TOR-regulated phosphoproteome and the regulation of cellular protein synthesis

Project description:We describe an in depth analysis in fission yeast of changes in the phosphoproteome after inhibition of the TOR protein kinases. A total of 756 phosphosites on 316 proteins showed significant and rapid changes in phosphorylation levels after TOR kinase inhibition when the rate of protein synthesis reduced by 90%. These proteins were involved in a range of cellular processes including 4 that featured strongly: signalling-related processes, translation, cell polarity and actin cytoskeletal organisation, and vesicle-mediated transport and autophagy. We propose that these processes have major roles in TOR regulated cellular growth control. We also show that the S6 protein kinases have no role in immediate TOR regulated cellular protein synthesis, but in contrast there is a role for Tif471, the translation initiation factor homologue of eIF4G. This protein becomes rapidly phosphorylated after TORC1 inhibition in particular, but if that phosphorylation is prevented, as demonstrated by mutations on the specific phosphosites, the inhibition of protein synthesis rate is reduced. We propose that this factor is a downstream target of the TOR pathway, with a role in partially regulating global cellular protein synthesis.

2021-07-09 | PXD023664 | Pride

Nitrogen starvation leads to TOR kinase-mediated downregulation of fatty acid synthesis in the algae Chlorella sorokiniana and Chlamydomonas reinhardtii

Project description:The accumulation of triacylglycerol (TAG) as a storage compound in eukaryotic algae has been the subject of extensive studies over the last 25 years. The model industrial alga Chlorella sorokiniana accumulates TAG and other storage compounds under nitrogen (N)-limited growth. Previously we used transcriptomics to explore the regulation of TAG synthesis in C. sorokiniana. Surprisingly, our analysis showed that the expression of several key genes encoding enzymes involved in plastidic fatty acid synthesis are significantly repressed. Metabolic labeling with radiolabeled acetate showed that de novo fatty acid synthesis is indeed downregulated under N-limitation. Likewise, inhibition of the Target of Rapamycin kinase (TOR), a key regulator of metabolism and growth, decreased fatty acid synthesis. We compared the changes induced in the quantitative proteome and phosphoproteome of cells under N-limitation or TOR inhibition and found extensive overlap between the N-limited and TOR-inhibited conditions. We also detected variations in the phosphorylation of TOR complex proteins under N-limitation, indicating that TOR signaling is altered. Our results indicate that under N-limitation there is significant metabolic remodeling, including fatty acid synthesis, mediated by TOR signaling. We find that TOR-mediated metabolic remodeling of fatty acid synthesis under N-limitation is conserved in the chlorophyte algae Chlorella sorokiniana and Chlamydomonas reinhardtii.

2024-10-17 | PXD041691 | Pride

Tor tor

Project description:Tor tor overview

| PRJNA973154 | ENA

Differentially regulated genes in TOR knockdown Arabidopsis lines

Project description:Rapamycin-sensitive transgenic Arabidopsis lines (BP12) expressing yeast FK506 Binding Protein12 (FKBP12) were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf and shoot growth and development leading to poor nutrient uptake and light energy utilization. Genetic and physiological studies together with RNA-Seq and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and lifespan in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, ribosomal RNA and protein synthesis.

2012-12-18 | GSE42968 | GEO

Tor tor

Project description:Tor tor Partial genome sequencing

| PRJNA638510 | ENA

rnai tor time course - The signalization way TOR/PTEN in Arabidopsis

Project description:gnp_blan06_torpten - rnai tor time course - The impact of the TOR pathway on growth and stress responses. Modification of translational and transcriptional profiles in Tor-inducible RNAi mutants and identification of TOR targets.

2011-01-07 | GSE25701 | GEO

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