The study of bioactive compounds from marine animals has provided, over time, an endless source of interesting molecules. Jellyfish are commonly targets of study due to their toxic proteins. However, there is a gap in reviewing successful wet-lab methods employed in these animals, which compromises the fast progress in the detection of related biomolecules. Here, we provide a compilation of the most effective wet-lab methodologies for jellyfish venom extraction prior to proteomic analysis—separation, identification and toxicity assays. This includes SDS-PAGE, 2DE, gel chromatography, HPLC, DEAE, LC-MS, MALDI, Western blot, hemolytic assay, antimicrobial assay and protease activity assay. For a more comprehensive approach, jellyfish toxicity studies should further consider transcriptome sequencing. We reviewed such methodologies and other genomic techniques used prior to the deep sequencing of transcripts, including RNA extraction, construction of cDNA libraries and RACE. Overall, we provide an overview of the most promising methods and their successful implementation for optimizing time and effort when studying jellyfish.
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