Project description:The Crown-of-Thorns starfish (COTS), Acanthaster planci, is a highly fecund predator of reef-building corals distributed throughout the Indo-Pacific. COTS population outbreaks cause substantial loss of coral cover, diminishing the integrity and resilience of the reef ecosystems thus increasing their susceptibility to climate change. We sequenced genomes of A. planci from the Great Barrier Reef, Australia (GBR) and Okinawa, Japan (OKI) to guide identification of species-specific peptide communication with potential applications in mitigation strategies. The genome-encoded proteins excreted and secreted into the surrounding seawater by COTS forming aggregations and by those escaping the predatory giant triton snail, Charonia tritonis, were identified LC-MS/MS.
Project description:Sarcophyton soft coral samples collected in Palau 2019 (Dataset includes 83 crude extracts, with two technical replicates and two injections of each, plus 10 reference samples of cembrane diterpenes isolated from soft corals from Palau or Okinawa)
Project description:Soft corals are unique amongst animals in their prolific production of bioactive terpenoid natural products that rival the chemical diversity of plants and microbes. We recently established that octocorals uniformly express terpene cyclases and that their encoding genes often reside within putative biosynthetic gene clusters, a feature uncommon in animal genomes. In this work, we report the discovery and characterization of a widespread gene cluster family for the biosynthesis of briarane diterpenoids that number over 600 molecules distinct to corals. We sequenced five genomes from evolutionarily discrete families of briarane-producing octocorals, including the chromosomally resolved precious coral Corallium rubrum, and identified a common five-gene cluster composed of a terpene cyclase, three cytochrome P450s, and a short-chain dehydrogenase. Using Escherichia coli and Saccharomyces cerevisiae as hosts and homologous briarane biosynthesis genes from seven corals, we reconstituted the biosynthesis of cembrene B g-lactone, which contains the g-lactone structural feature distinctive of briarane diterpenoids. The discovery of the genomic basis of briarane biosynthesis not only allows for its biological examination across coral species but establishes that animals, like microbes and plants, also employ gene cluster families to produce specialized metabolites.
Project description:Soft corals (Cnidaria, Anthozoa, Octocorallia) are a diverse group of marine invertebrates that inhabit various marine environments in tropical and subtropical areas. Several species are recognized as prolific sources of compounds with a wide array of biological activities. Recent advances in analytical techniques, supported by robust statistical analyses, have allowed the analysis and characterization of the metabolome present in a single living organism. In this study, a liquid chromatography-high resolution mass spectrometry metabolomic approach was applied to analyze the metabolite composition of 28 soft corals present in the Caribbean coast of Colombia. Multivariate data analysis was used to correlate the chemical fingerprints of soft corals with their cytotoxic activity against tumor cell lines for anticancer purpose. Some diterpenoids were identified as specific markers to discriminate between cytotoxic and non-cytotoxic crude extracts of soft corals against tumor cell lines. In the models generated from the comparative analysis of PLS-DA for tumor lines, A549 and SiHa, the diterpene 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene yielded a high score in the variable importance in projection. These results highlight the potential of metabolomic approaches towards the identification of cytotoxic agents against cancer of marine origin. This workflow can be useful in several studies, mainly those that are time consuming, such as traditional bioprospecting of marine natural products.
Project description:ChIP-seq data characterizing the occupancy of TFAM over the mitochondrial and nuclear genomes in HeLa cells. Characterization of mitochondrial and nuclear genome-wide TFAM binding in HeLa cells
Project description:Metastatic breast cancer cells disseminate to organs with a soft microenvironment. Whether and how tissue mechanical properties influence their response to treatment remains unclear. Here we found that a soft ECM empowers redox homeostasis. Cells cultured on a soft ECM display increased peri-mitochondrial F-actin promoted by Spire1C and Arp2/3 nucleation factors, and increased DRP1- and MIEF1/2-dependent mitochondrial fission. Changes in mitochondrial dynamics lead to increased mtROS production and activate the NRF2 antioxidant transcriptional response, including increased cystine uptake and glutathione metabolism. This retrograde response endows cells with resistance to oxidative stress and ROS-dependent chemotherapy drugs. This is relevant in a mouse model of metastatic breast cancer cells dormant in the lung soft tissue, where inhibition of DRP1 and NRF2 restored cisplatin sensitivity and prevented disseminated cancer cell awakening. We propose that targeting this mitochondrial dynamics- and redox-based mechanotransduction pathway could open new avenues to prevent metastatic relapse.