Project description:An Infinium microarray platform (HorvathMammalMethylChip320) was used to generate DNA methylation data from n=48 liver samples from mice. Treatment: encapsulated rapamycin treated or control mice
Project description:Dynamic mRNA gene expression from the wildtype YSBN6 during a rapamycin treatment (rapamycin-induced downshift). Rapamycin was added to yeast cells growing exponentially on glutamine as sole nitrogen source.
Project description:Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer. Keywords: drug treatment
Project description:p73 is a p53 family transcription factor that plays critical roles during development and tumor suppression. We analyzed p73 activity using a combination of ChIP-on-Chip and gene expression profiling, both at baseline and after treatment with the mTOR inhibitor rapamycin. We report the first comprehensive analysis of p73 binding across the genome. Furthermore, we re-analyzed this p73 cistrome after perturbation with rapamycin, an inhibitor of mTOR and inducer of p73. Multiple determinants of p73 binding, activity, and function were evident, and were modulated by mTOR.
Project description:The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid the adverse side-effects of clinical dosing regimes. Here we show a profound memory effect of brief rapamycin treatment. Brief, early adult treatment extended lifespan in Drosophila to the same degree as lifelong dosing. Lasting memory of earlier rapamycin treatment was mediated by elevated autophagy in enterocytes of the gut, accompanied by increased intestinal spermidine levels and improved structure and function of the ageing intestine. Brief elevation of autophagy itself induced a long-term increase in autophagy. In mice, short-term, 3-month treatment also induced a full memory effect, with enhanced autophagy in Paneth cells, improved Paneth cell architecture and gut barrier function at levels induced by chronic treatment, even 6 months after rapamycin was withdrawn. Past rapamycin treatment also enhanced the regenerative potential of aged intestine in intestinal organoids. Full geroprotective effects of chronic rapamycin treatment can thus be obtained with a brief pulse of the drug.
Project description:Dynamic mRNA gene expression from the wildtype YSBN6 during a rapamycin treatment (rapamycin-induced downshift). Rapamycin was added to yeast cells growing exponentially on glutamine as sole nitrogen source. A sample was taken at steady-state 10 minutes before , and then 3, 7, 10, 14, 24, 56 and 120 minutes after rapamycin treatment. Biological triplicate gene expression was measured for samples -10, 7 and 24 minutes after shift, for a total of 14 chips. Changes were generally evaluated relative to the steady-state point (-10 minutes). Biological variability can be assessed from the replicates time points. Other dynamic omics data are associated with this dataset. Consult the publication for more details.
Project description:Analysis of HiC genome wide chromosomal interaction data in the context of replicative senescence, rapamycin treatment, the withdrawal of rapamycin, and with p65 inhibition in rapamycin withdrawal. This was done in order to determine what changes in chromosomal architecture occur during replicative senescence, and what impact rapamycin treatment or withdrawal or p65 inhibition has upon these changes.
Project description:Rapamycin treatment reduced stool and colon histological scores in B27-Tg rats compared to vehicle-treated B27-Tg controls. Transcriptome analysis revealed that rapamycin reduced expression of key pro-inflammatory cytokines like Il17a, Il17f, Tnf, Il1a, IL1b, and Il22 in B27-Tg colon tissue compared to vehicle-treated B27-Tg controls. Ex vivo treatment of bulk immune cells isolated from B27-Tg rat colon with rapamycin (25 and 50 nM) reduced expression of Il17a, Il17f, Ifng, and Il22 compared to vehicle-treated cells. Rapamycin treatment decreased the abundance of cecum microbiota associated with inflammation in B27-Tg rats. Rapamycin also altered the gut microbiome in WT rats, without associated changes in the tissue transcriptome. Our study demonstrates that rapamycin treatment substantially reduces HLA-B27-mediated gut inflammation in experimental SpA. Results from this pre-clinical model suggest further evaluation of rapamycin as a therapeutic strategy in HLA-B27 associated diseases is warranted.
Project description:p73 is a p53 family transcription factor that plays critical roles during development and tumor suppression. We analyzed p73 activity using a combination of ChIP-on-Chip and gene expression profiling, both at baseline and after treatment with the mTOR inhibitor rapamycin. This SuperSeries is composed of the SubSeries listed below.