Proteomics and metabolomics systems analysis of envenomation by Bothrops snakes and antivenom effects using a murine model
Final Report Abstract
Animal venoms comprise many toxins that act in concert to break apart the highly robust homeostatic systems of prey organisms. On the other hand, prey organisms actively antagonize each step of the envenomation phenomenon, which displays a complex kinetics involving important changes at molecular, cell, tissue and organism levels. The challenges for studying venoms and envenomation comprehend two hurdles: first, to analyze, isolate and chemically characterize the variety of toxin molecules in natural venoms; second, to uncover molecular mechanisms underlying the dynamics of envenomation, which includes systemic responses progressing from local cells and tissues up to the entire organism. Omics-style investigation of individual snake venom metalloproteinases (SVMP) activities on complex biological systems has proven useful for the evaluation of several aspects of the pathology of the snake envenomation, as well as the in vivo effects triggered by SVMPs. In this context, the present project has expanded the systems analysis of mammalian host response to complex toxins rather than individual components, by applying proteomics and metabolomics approaches to explore the in vivo effects of Bothrops jararaca venom in the muscle, serum, kidneys, lungs, and liver of mice. Considering the worldwide burden of snakebite death and disability, which is recognized by the WHO as a tropical neglected disease, and the crucial role of antivenom in its treatment, the impact of anti-bothropic antivenom in the systemic venom effects has also been evaluated.
Publications
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A Systematic Evaluation of Semispecific Peptide Search Parameter Enables Identification of Previously Undescribed N-Terminal Peptides and Conserved Proteolytic Processing in Cancer Cell Lines. Proteomes, 9(2), 26.
Fahrner, Matthias; Kook, Lucas; Fröhlich, Klemens; Biniossek, Martin L. & Schilling, Oliver
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Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity. Nature Communications, 13(1).
Fröhlich, Klemens; Brombacher, Eva; Fahrner, Matthias; Vogele, Daniel; Kook, Lucas; Pinter, Niko; Bronsert, Peter; Timme-Bronsert, Sylvia; Schmidt, Alexander; Bärenfaller, Katja; Kreutz, Clemens & Schilling, Oliver
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MaxQuant and MSstats in Galaxy Enable Reproducible Cloud-Based Analysis of Quantitative Proteomics Experiments for Everyone. Journal of Proteome Research, 21(6), 1558-1565.
Pinter, Niko; Glätzer, Damian; Fahrner, Matthias; Fröhlich, Klemens; Johnson, James; Grüning, Björn Andreas; Warscheid, Bettina; Drepper, Friedel; Schilling, Oliver & Föll, Melanie Christine
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Systemic toxicity of snake venom metalloproteinases: Multi-omics analyses of kidney and blood plasma disturbances in a mouse model. International Journal of Biological Macromolecules, 253, 127279.
Trevisan-Silva, Dilza; Cosenza-Contreras, Miguel; Oliveira, Ursula C.; da Rós, Nancy; Andrade-Silva, Débora; Menezes, Milene C.; Oliveira, Ana Karina; Rosa, Jaqueline G.; Sachetto, Ana T.A.; Biniossek, Martin L.; Pinter, Niko; Santoro, Marcelo L.; Nishiyama-Jr, Milton Y.; Schilling, Oliver & Serrano, Solange M.T.
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Size exclusion chromatography based proteomic and degradomic profiling of inflammasome-activated, murine bone marrow-derived dendritic cells highlights complex retention and release of cleavage products. Molecular Omics, 20(9), 595-610.
Vogele, Daniel; Wöhrle, Svenja; Saller, Benedikt S.; Fröhlich, Klemens; Barta, Bálint András; Cosenza-Contreras, Miguel; Groß, Olaf & Schilling, Oliver
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TermineR: Extracting information on endogenous proteolytic processing from shotgun proteomics data. PROTEOMICS, 24(19).
Cosenza‐Contreras, Miguel; Seredynska, Adrianna; Vogele, Daniel; Pinter, Niko; Brombacher, Eva; Cueto, Ruth Fiestas; Dinh, Thien‐Ly Julia; Bernhard, Patrick; Rogg, Manuel; Liu, Junwei; Willems, Patrick; Stael, Simon; Huesgen, Pitter F.; Kuehn, E. Wolfgang; Kreutz, Clemens; Schell, Christoph & Schilling, Oliver
