Project description:Ethyl carbamate is a common food contaminant prevalent in fermented food with probable carcinogenic effects in animals. To date, other toxicological properties of ethyl carbamate are not well characterized. Using the genetic model Caenorhabditis elegans, we found that chronic exposure to ethyl carbamate during larval development inhibits growth while exposure at adulthood inhibits reproduction, shortens lifespan, and promotes degeneration of dopaminergic neurons. Through whole-transcriptome RNA-sequencing, we found that ethyl carbamate invokes a widespread transcriptomic response inducing the differential expression of > 4,000 genes by at least 2-fold. Functional analysis of RNA-sequencing data revealed that genes up-regulated enrich to various neuron regulatory processes and xenobiotic defense. Gene expression analysis confirms that various genes functioning within phase 1 and 2 detoxification responses along with ABC transporters are highly up-regulated in response to ethyl carbamate exposure, suggesting the induction of oxidative stress. Overall, these findings demonstrates new toxicological properties of chronic ethyl carbamate exposure and provide new insights into the effects in has on transcriptome regulation in the C. elegans model.
Project description:We studied the effect of diet-induced obesity on the transcriptional profile of the adrenal cortex. We also studied the effect of icosapent ethyl on the transcriptome of the adrenal cortex of obese mice.
Project description:To elucidate the molecular mechanism underlying lifespan reduction induced by PM2.5 exposure in Caenorhabditis elegans, we performed global gene expression profiling by RNA-sequencing technology, and compared the gene expression pattern change induced by PM2.5 exposure.
Project description:Organisms' ability to respond to life-threatening environmental impacts is crucial for their survival. While acute stress responses to unfavorable factors are well known, the physiological consequences of transient stress experiences over time, as well as their underlying mechanisms, are not well understood. In this study, we investigated the long-term effects of a short heat shock (HS) exposure on the transcriptome of C. elegans. We found that the canonical HS response was followed by a profound transcriptional reprogramming affecting many genes involved in innate immunity response. This reprogramming relies on the endoribonuclease ENDU-2 but not the heat shock factor 1 (HSF-1). ENDU-2 in this context co-localizes with chromatin and interacts with RNA polymerase Pol II, enabling specific regulation of transcription in the post-HS period. Failure to activate this post-HS response does not impair animal survival under continuous HS insult but eliminates the beneficial effects of hormetic HS. In summary, our work discovers that the RNA-binding protein ENDU-2 mediates the hormetic long-term effects of transient HS to determine aging and longevity.
Project description:We have established epidermal expression of chil-27p::GFP as the marker for activation of oomycete recognition response (ORR) in C. elegans. Through a forward genetic screen, we identified clec-27, clec-35, and ceh-37 to be the key players required for activating chil-27p::GFP upon exposure to the oomycete Myzocytiopsis humicola extract. To determine if activation of entire ORR is affected in these mutants, we analyzed their transcriptome in the presence and absence of extract and compared with that of wildtype C. elegans.
Project description:We used microarrays to explore the global affect on gene expression in C. elegans after exposure to arsenic L3 stage N2 worms were incubated for 6 hrs in sodium arsenite containing media of concentrations .003 and .03. Three independent extractions of RNA were performed from no exposure, .003 exposure, and .03 exposure worms.
Project description:We provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of quizalofop-p-ethyl, isoxaflutole and mesotrione