Snake venom; a potent soup of biochemicals
Avondlezing door dr. Jeroen Kool, georganiseerd door de Bossche Chemische Kring
Samenvatting
The presentation “Venom Analytics with Integrated Bioassaying” by Dr. Jeroen Kool focuses on a multidisciplinary analytical approach to understanding venom toxins through integrated in vitro and in vivo bioassaying. This research aims to elucidate the structure-function relationships of venom components by employing high-resolution nanofractionation analytics, targeted ion channel bioassays, and zebrafish behavioral models.
The study leverages liquid chromatography separation, nanofractionation, and mass spectrometry detection to generate high-resolution venom toxin profiles. These fractionated toxins undergo subsequent cellular and zebrafish-based assays to assess their effects on ion channels and neurotoxic pathways. The integration of high-throughput venomics allows for precise toxin identification, correlating molecular data with observed bioactivity.
The zebrafish model serves as a key tool for evaluating neurotoxic effects in an ethically acceptable, high-throughput manner. By exposing zebrafish larvae to fractionated venom toxins, researchers can monitor locomotor responses, paralysis, and acute toxicity. This approach enables the construction of bioactivity-linked chromatographic profiles, identifying key venom constituents responsible for neurotoxic effects.
Additionally, the research incorporates ion channel bioassays, such as the α7 nicotinic acetylcholine receptor calcium influx assay, to evaluate the interaction of venom toxins with specific receptor targets. These bioassays, performed in parallel with nanofractionation and MS detection, help characterize toxin-receptor interactions at a molecular level.
Beyond functional characterization, high-throughput venomics will be discussed and accelerates the identification and comparative analysis of venom compositions. This is particularly relevant for snakebite envenomation, where understanding venom variability is crucial for developing more effective antivenoms and therapeutic interventions. The presentation follows up with discussing our most recent advancement in venomics: Venom Variation Venomics (VVV), which enables rapid intraspecies venom variation analysis and will be demonstrated for the snake species Crotalus viridis viridis, examining factors like geographical location, seasonal shifts, and individual genetic differences in relation to venom composition.
By combining advanced bioanalytical techniques, in vivo models, and high-throughput venomics, this research provides a comprehensive framework for venom profiling, facilitating both toxin discovery and translational applications in pharmacology and antivenom development. The findings contribute to a deeper understanding of venom bioactivity and underscore the potential of integrated analytics in toxinology research.
About Dr. Jeroen Kool
Dr. Jeroen Kool is an analytical chemist with research interests in high resolution screening of biologically active mixtures. His research achievements allow full compatibility of analytical separations with biological assays (including cellular) and parallel MS detection for investigation of bioactive mixtures (environmental mixtures, natural product extracts, metabolic mixtures, venoms) using miniaturized setups and nanospotting technologies. These techniques combining chromatography, mass spectrometry and bioassays in one analytical platform are now known as nanofractionation analytics.
He developed hyphenated analytics for both LC and GC separations to bioassays for identification of biologically active toxicants in the environment, natural extracts, in foods. In case of GC fractionations, we developed and patented an automated system for high resolution fractionation of complete GC chromatograms with parallel MS detection. Dr. Kool also developed analytical methodologies for bioactivity profiling of metabolic mixtures from drugs and lead compounds targeting GPCRs, nuclear receptors, protein kinases and ion channels. We are now investigating metabolic mixtures of drugs of abuse and of New Psychoactive Substances. These “recreational” drugs and their metabolites unfortunately also end up in our waste waters and as such need attention in analytical and environmental research.
Our recent research efforts focus on: 1) High Throughput venomics, which is able to rapidly and almost fully automated characterize venoms in terms of venom composition. 2) Integrated nanofractionation analytics for in vitro targeted and in vivo phenotypic zebrafish bioassaying of all toxins in venoms. 3) Venom Variation Venomics (VVV). 4) Analytics for characterization of venom induced pathologies in order to better understand snakebite envenoming and as such develop better treatment strategies based on small molecular drugs.
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