Project description:Long-lived genetic mutants from different pathways of lifespan extension were used to determine the extent to which there are common downstream mediators of longevity. We have previously obtained RNA-sequencing data from other long-lived mutants including sod-2, clk-1, isp-1, nuo-6 and daf-2. Gene expression will be compared between these nine long-lived mutants.
Project description:Analysis of gene expression in two long-lived daf-2 mutant (mutation in the insulin/IGF-1 receptor) and eat-2 mutant (caloric restriction model), comparison of gene expression profiles of two long-lived mutants provide novel insight into longevity Impaired insulin/IGF-1 signaling (IIS) pathway and caloric restriction (CR) are two well-established interventions to prolong lifespan in worm C. elegans. Although many studies using “-omics” approaches have gained informative knowledges on key longevity regulators in either IIS or CR models, few of those investigated the shared regulators between these two longevity interventions and integrated the messages from different –omics studies. In this study, we aimed to identify key pathways and metabolite fingerprints of longevity shared between the two interventions in worms using a multi-omics integration approach. We collected transcriptomics and metabolomics data from two long-lived mutant worm strains, i.e. daf-2 (impaired IIS pathway) and eat-2 (CR model) and compared with N2 strain. We detected many key pathways that were upregulated at the gene expression level in both long-lived mutants, such as defense response and lipid storage, while synthesis of macromolecules and developmental processes were downregulated at the transcript level. From our polar metabolite analysis, we discovered several shared metabolic features between the two long-lived mutants, including glycerol-3P, adenine, xanthine and AMP. In addition, we detected a lowered amino acid pool and two fatty acid species, C18:0 and C17:1, that behaved similarly in both long-lived mutants. After we integrated transcriptomics and metabolomics data based on the annotations in KEGG, our results highlighted a downregulation of pyrimidine metabolism and upregulation of purine metabolism in both long-lived mutants compared to N2 worms. Overall, our findings point towards the existence of shared metabolic pathways that are important for lifespan extension and provide novel insight of potential regulators and metabolic fingerprints for longevity.
Project description:Investigation of whole genome gene expression level changes in C. elegans eat-2; acs-22 and eat-2; pmk-1; acs-22 mutant compared to the eat-2 strain.
Project description:Investigation of whole genome gene expression level changes in C. elegans ptr-8 eat-2; acs-20 compared to the eat-2; acs-20 mutant. This project contains 6 samples (3 from eat-2; acs-20, 3 from ptr-8 eat-2; acs-20) of RNA-seq data.
Project description:Investigation of whole genome gene expression level changes in C. elegans eat-2, acs-20 and eat-2; acs-20 mutant compared to the wild-type N2 strain.
Project description:To identify genes whose expression in Caenorhabditis elegans is regulated by mbk-1 (ortholog of the human protein kinase DYRK1A implicated in Down syndrome) during adulthood, we performed whole transcriptome RNA-sequencing (RNA-seq) on mbk-1(+) and mbk-1(-) worms. To further account for the influence of genetic background on mbk-1 function, these experiments were conducted in long-lived insulin-receptor defective [daf-2(-)] or germline stem cell [GSC] deficient [glp-1(-), i.e. GSC(-)] strains, as well as in corresponding [i.e daf-2(+) or glp-1(+)/GSC(+)] control strains.
Project description:Obesity and its co-morbidities, such as diabetes and hypertension, can significantly reduce a person’s quality of life and place huge pressure on healthcare resources. When we eat a meal our gut and brain release hormones to control the amount of food and fluid we ingest to prevent overeating. One of these hormones is called glucagon-like peptide 1 (GLP-1) and is released from intestinal cells in response to food intake, but also produced and released in the brain. Drug analogues of GLP-1 are already in use in the clinic to treat both diabetes and obesity. The aim of this work was to obtain fundamental knowledge about a GLP-1 receptor population in nerve terminals of the posterior pituitary gland. We have investigated the pharmacological actions of GLP-1 using a selective receptor agonist called liraglutide, a drug that is approved for diabetes and obesity treatment in humans. Our work has focussed on the phosphoproteome of the neurointermediate lobe (posterior pituitary + intermediate lobe) of the rat pituitary gland 30 minutes after intraperitoneal injection of liraglutide (100 µg/kg) compared to vehicle controls (n = 6 animals per group). New understanding of this GLP-1 receptor population is essential for our knowledge of current treatments of diabetes and obesity that use stable peptide analogues in humans.
Project description:Oncostatin M (OSM) and Leukemia Inhibitory Factor (LIF) signal within cells via the gp130 (Il6st) coreceptor bound either to the LIF receptor (LIFR) or the oncostatin M receptor (OSMR), but whether murine OSM can act through both receptors is controversial. Both LIF and OSM stimulate bone formation, inhibit adipocyte differentiation, and promote osteoclast differentiation, but our earlier work suggested this may depend on the receptor subtype used. This project aimed to identify those gene targets regulated by murine OSM via OSMR and LIFR by using wild type and OSMR null primary osteoblasts. Cells were differentiated to their most mature state (i.e. osteocytes) because the only prior target gene known to be regulated by murine OSM via the LIFR was an osteocyte-specific gene, sclerostin.