Project description:Gene expression profiles of WT, jaz9 and jaz10 mutant treated with mock or with 3, 6, or 8 was performed using the custom microarray Agilent-034592 The experiments were designed to explore the effect of antagonist of jasmonate perception in WT and two mutants
Project description:In plants, recognition of immunogenic molecular patterns, such as bacterial flagellin (flg22 epitope), leads to an enhanced state of immunity, designated pattern-triggered immunity (PTI). Following cognate ligand perception, pattern recognition receptors initiate sequential phosphorylation events to activate defense responses against invading pathogens. To gain further insight into PTI signaling, we conducted phosphoproteome analyses in Arabidopsis seedlings with immunogenic molecular patterns.
Project description:Jasmonates regulate plant development and defence. In angiosperms, the canonical bioactive jasmonate is jasmonoyl-isoleucine (JA-Ile), which is formed in Arabidopsis thaliana by JAR1 and GH3.10. In contrast to other jasmonate biosynthesis or perception mutants, however, gh3.10 jar1 knockout lines are still fertile. Therefore we investigated whether further jasmonates and GH3 enzymes contribute to regulation of fertility. This study found JAR1 and GH3.10 are the only contributors to JA-Ile biosynthesis in Arabidopsis and identified a number of JA conjugates as potential bioactive jasmonates acting in the absence of JA-Ile. However, their contribution in regulating fertility is yet to be conclusively determined. Transcriptomic analysis did not identify further GH3 enzymes with increased transcription rate in flowers of gh3.10 jar1 plants.
Project description:This study evaluates the transcriptome of Arabidopsis thaliana seedlings (Col-0 ecotype) treated with methyl jasmonate (MeJA) or with the salicylic acid analog benzothiadiazole (BTH).
Project description:Clinical resistance such as androgen receptor (AR) mutation, AR overexpression, and AR splice variants (ARVs) restrict the second-generation antiandrogens benefit in patients with castration-resistant prostate cancer (CRPC). Several strategies have been implemented to develop novel antiandrogens to circumvent the occurring resistance. In this study, based on rational drug design, we discovered and identified a bifunctional small molecule Z15 as a potent AR antagonist and AR selective degrader. Z15 could directly bind to the AR ligand-binding domain (LBD) and inhibited DHT-induced AR nuclear translocation. Furthermore, Z15 promoted AR degradation through the proteasome pathway. As a result, our in vitro and in vivo studies showed Z15 efficiently suppressed AR and AR mutant transcription activity, downregulated mRNA and protein levels of AR target genes, as well as overcame AR LBD mutations, AR amplification, and ARVs-induced resistance in CRPC. In conclusion, our data illustrate the synergistic importance of AR antagonism and degradation in advanced prostate cancer treatment.
Project description:RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by the relative lack of methods for the analysis of small molecule-RNA interactions. Here we present our efforts to develop such a platform using photoaffinity labeling. This technique, termed Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq), enables the rapid identification of small molecule binding locations within their RNA targets and can provide information on ligand selectivity across multiple different RNAs. These data, when supplemented with small molecule SAR data and RNA probing data enables the construction of a computational model of the RNA-ligand structure, thereby enabling the rational design of novel RNA-targeted ligands.