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Dr. Eivind A. B. Undheim
Centre for Biodiversity Dynamics, Department of Biology, NTNU, N-7491 Trondheim, Norway

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0 Phylogenetics
0 Structure-function relationships
0 venoms-based drug discovery
0 Animal venoms and toxins
0 Molecular evolution of venoms

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Animal venoms and toxins
Molecular evolution of venoms
venoms-based drug discovery
Venom transcriptomics

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Journal article
Published: 29 June 2021 in Toxins
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Phylum Cnidaria is an ancient venomous group defined by the presence of cnidae, specialised organelles that serve as venom delivery systems. The distribution of cnidae across the body plan is linked to regionalisation of venom production, with tissue-specific venom composition observed in multiple actiniarian species. In this study, we assess whether morphological variants of tentacles are associated with distinct toxin expression profiles and investigate the functional significance of specialised tentacular structures. Using five sea anemone species, we analysed differential expression of toxin-like transcripts and found that expression levels differ significantly across tentacular structures when substantial morphological variation is present. Therefore, the differential expression of toxin genes is associated with morphological variation of tentacular structures in a tissue-specific manner. Furthermore, the unique toxin profile of spherical tentacular structures in families Aliciidae and Thalassianthidae indicate that vesicles and nematospheres may function to protect branched structures that host a large number of photosynthetic symbionts. Thus, hosting zooxanthellae may account for the tentacle-specific toxin expression profiles observed in the current study. Overall, specialised tentacular structures serve unique ecological roles and, in order to fulfil their functions, they possess distinct venom cocktails.

ACS Style

Lauren Ashwood; Michela Mitchell; Bruno Madio; David Hurwood; Glenn King; Eivind Undheim; Raymond Norton; Peter Prentis. Tentacle Morphological Variation Coincides with Differential Expression of Toxins in Sea Anemones. Toxins 2021, 13, 452 .

AMA Style

Lauren Ashwood, Michela Mitchell, Bruno Madio, David Hurwood, Glenn King, Eivind Undheim, Raymond Norton, Peter Prentis. Tentacle Morphological Variation Coincides with Differential Expression of Toxins in Sea Anemones. Toxins. 2021; 13 (7):452.

Chicago/Turabian Style

Lauren Ashwood; Michela Mitchell; Bruno Madio; David Hurwood; Glenn King; Eivind Undheim; Raymond Norton; Peter Prentis. 2021. "Tentacle Morphological Variation Coincides with Differential Expression of Toxins in Sea Anemones." Toxins 13, no. 7: 452.

Journal article
Published: 12 June 2021 in Toxicon: X
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Snakebite envenoming is a neglected tropical disease that may claim over 100,000 human lives annually worldwide. Snakebite occurs as the result of an interaction between a human and a snake that elicits either a defensive response from the snake or, more rarely, a feeding response as the result of mistaken identity. Snakebite envenoming is therefore a biological and, more specifically, an ecological problem. Snake venom itself is often described as a “cocktail”, as it is a heterogenous mixture of molecules including the toxins (which are typically proteinaceous) responsible for the pathophysiological consequences of envenoming. The primary function of venom in snake ecology is pre-subjugation, with defensive deployment of the secretion typically considered a secondary function. The particular composition of any given venom cocktail is shaped by evolutionary forces that include phylogenetic constraints associated with the snake's lineage and adaptive responses to the snake's ecological context, including the taxa it preys upon and by which it is predated upon. In the present article, we describe how conceptual frameworks from ecology and evolutionary biology can enter into a mutually enlightening relationship with clinical toxinology by enabling the consideration of snakebite envenoming from an “ecological stance”. We detail the insights that may emerge from such a perspective and highlight the ways in which the high-fidelity descriptive knowledge emerging from applications of -omics era technologies – “venomics” and “antivenomics” – can combine with evolutionary explanations to deliver a detailed understanding of this multifactorial health crisis.

ACS Style

Juan J. Calvete; Bruno Lomonte; Anthony J. Saviola; Fabián Bonilla; Mahmood Sasa; David J. Williams; Eivind A.B. Undheim; Kartik Sunagar; Timothy N.W. Jackson. Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance. Toxicon: X 2021, 9-10, 100070 .

AMA Style

Juan J. Calvete, Bruno Lomonte, Anthony J. Saviola, Fabián Bonilla, Mahmood Sasa, David J. Williams, Eivind A.B. Undheim, Kartik Sunagar, Timothy N.W. Jackson. Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance. Toxicon: X. 2021; 9-10 ():100070.

Chicago/Turabian Style

Juan J. Calvete; Bruno Lomonte; Anthony J. Saviola; Fabián Bonilla; Mahmood Sasa; David J. Williams; Eivind A.B. Undheim; Kartik Sunagar; Timothy N.W. Jackson. 2021. "Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance." Toxicon: X 9-10, no. : 100070.

Journal article
Published: 05 February 2021 in Nature Communications
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Venoms have evolved over a hundred times in animals. Venom toxins are thought to evolve mostly by recruitment of endogenous proteins with physiological functions. Here we report phylogenetic analyses of venom proteome-annotated venom gland transcriptome data, assisted by genomic analyses, to show that centipede venoms have recruited at least five gene families from bacterial and fungal donors, involving at least eight horizontal gene transfer events. These results establish centipedes as currently the only known animals with venoms used in predation and defence that contain multiple gene families derived from horizontal gene transfer. The results also provide the first evidence for the implication of horizontal gene transfer in the evolutionary origin of venom in an animal lineage. Three of the bacterial gene families encode virulence factors, suggesting that horizontal gene transfer can provide a fast track channel for the evolution of novelty by the exaptation of bacterial weapons into animal venoms.

ACS Style

Eivind A. B. Undheim; Ronald A. Jenner. Phylogenetic analyses suggest centipede venom arsenals were repeatedly stocked by horizontal gene transfer. Nature Communications 2021, 12, 1 -14.

AMA Style

Eivind A. B. Undheim, Ronald A. Jenner. Phylogenetic analyses suggest centipede venom arsenals were repeatedly stocked by horizontal gene transfer. Nature Communications. 2021; 12 (1):1-14.

Chicago/Turabian Style

Eivind A. B. Undheim; Ronald A. Jenner. 2021. "Phylogenetic analyses suggest centipede venom arsenals were repeatedly stocked by horizontal gene transfer." Nature Communications 12, no. 1: 1-14.

Report
Published: 21 January 2021 in Science
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Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

ACS Style

T. D. Kazandjian; D. Petras; S. D. Robinson; J. van Thiel; H. W. Greene; K. Arbuckle; A. Barlow; D. A. Carter; R. M. Wouters; G. Whiteley; S. C. Wagstaff; A. S. Arias; L.-O. Albulescu; A. Plettenberg Laing; C. Hall; A. Heap; S. Penrhyn-Lowe; C. V. McCabe; S. Ainsworth; R. R. da Silva; P. C. Dorrestein; M. K. Richardson; J. M. Gutiérrez; J. J. Calvete; R. A. Harrison; I. Vetter; E. A. B. Undheim; W. Wüster; N. R. Casewell. Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science 2021, 371, 386 -390.

AMA Style

T. D. Kazandjian, D. Petras, S. D. Robinson, J. van Thiel, H. W. Greene, K. Arbuckle, A. Barlow, D. A. Carter, R. M. Wouters, G. Whiteley, S. C. Wagstaff, A. S. Arias, L.-O. Albulescu, A. Plettenberg Laing, C. Hall, A. Heap, S. Penrhyn-Lowe, C. V. McCabe, S. Ainsworth, R. R. da Silva, P. C. Dorrestein, M. K. Richardson, J. M. Gutiérrez, J. J. Calvete, R. A. Harrison, I. Vetter, E. A. B. Undheim, W. Wüster, N. R. Casewell. Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science. 2021; 371 (6527):386-390.

Chicago/Turabian Style

T. D. Kazandjian; D. Petras; S. D. Robinson; J. van Thiel; H. W. Greene; K. Arbuckle; A. Barlow; D. A. Carter; R. M. Wouters; G. Whiteley; S. C. Wagstaff; A. S. Arias; L.-O. Albulescu; A. Plettenberg Laing; C. Hall; A. Heap; S. Penrhyn-Lowe; C. V. McCabe; S. Ainsworth; R. R. da Silva; P. C. Dorrestein; M. K. Richardson; J. M. Gutiérrez; J. J. Calvete; R. A. Harrison; I. Vetter; E. A. B. Undheim; W. Wüster; N. R. Casewell. 2021. "Convergent evolution of pain-inducing defensive venom components in spitting cobras." Science 371, no. 6527: 386-390.

Journal article
Published: 14 May 2020 in Toxins
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A critical hurdle in ant venom proteomic investigations is the lack of databases to comprehensively and specifically identify the sequence and function of venom proteins and peptides. To resolve this, we used venom gland transcriptomics to generate a sequence database that was used to assign the tandem mass spectrometry (MS) fragmentation spectra of venom peptides and proteins to specific transcripts. This was performed alongside a shotgun liquid chromatography–mass spectrometry (LC-MS/MS) analysis of the venom to confirm that these assigned transcripts were expressed as proteins. Through the combined transcriptomic and proteomic investigation of Paraponera clavata venom, we identified four times the number of proteins previously identified using 2D-PAGE alone. In addition to this, by mining the transcriptomic data, we identified several novel peptide sequences for future pharmacological investigations, some of which conform with inhibitor cysteine knot motifs. These types of peptides have the potential to be developed into pharmaceutical or bioinsecticide peptides.

ACS Style

Samira R. Aili; Axel Touchard; Regan Hayward; Samuel D. Robinson; Sandy S. Pineda; Hadrien Lalagüe; Irina Vetter; Eivind A. B. Undheim; R. Manjunatha Kini; Pierre Escoubas; Matthew P. Padula; Garry S. A. Myers; Graham M. Nicholson. An Integrated Proteomic and Transcriptomic Analysis Reveals the Venom Complexity of the Bullet Ant Paraponera clavata. Toxins 2020, 12, 324 .

AMA Style

Samira R. Aili, Axel Touchard, Regan Hayward, Samuel D. Robinson, Sandy S. Pineda, Hadrien Lalagüe, Irina Vetter, Eivind A. B. Undheim, R. Manjunatha Kini, Pierre Escoubas, Matthew P. Padula, Garry S. A. Myers, Graham M. Nicholson. An Integrated Proteomic and Transcriptomic Analysis Reveals the Venom Complexity of the Bullet Ant Paraponera clavata. Toxins. 2020; 12 (5):324.

Chicago/Turabian Style

Samira R. Aili; Axel Touchard; Regan Hayward; Samuel D. Robinson; Sandy S. Pineda; Hadrien Lalagüe; Irina Vetter; Eivind A. B. Undheim; R. Manjunatha Kini; Pierre Escoubas; Matthew P. Padula; Garry S. A. Myers; Graham M. Nicholson. 2020. "An Integrated Proteomic and Transcriptomic Analysis Reveals the Venom Complexity of the Bullet Ant Paraponera clavata." Toxins 12, no. 5: 324.

Journal article
Published: 12 May 2020 in Proceedings of the National Academy of Sciences
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Spiders are one of the most successful venomous animals, with more than 48,000 described species. Most spider venoms are dominated by cysteine-rich peptides with a diverse range of pharmacological activities. Some spider venoms contain thousands of unique peptides, but little is known about the mechanisms used to generate such complex chemical arsenals. We used an integrated transcriptomic, proteomic, and structural biology approach to demonstrate that the lethal Australian funnel-web spider produces 33 superfamilies of venom peptides and proteins. Twenty-six of the 33 superfamilies are disulfide-rich peptides, and we show that 15 of these are knottins that contribute >90% of the venom proteome. NMR analyses revealed that most of these disulfide-rich peptides are structurally related and range in complexity from simple to highly elaborated knottin domains, as well as double-knot toxins, that likely evolved from a single ancestral toxin gene.

ACS Style

Sandy S. Pineda; Yanni K.-Y. Chin; Eivind A. B. Undheim; Sebastian Senff; Mehdi Mobli; Claire Dauly; Pierre Escoubas; Graham M. Nicholson; Quentin Kaas; Shaodong Guo; Volker Herzig; John S. Mattick; Glenn F. King. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene. Proceedings of the National Academy of Sciences 2020, 117, 11399 -11408.

AMA Style

Sandy S. Pineda, Yanni K.-Y. Chin, Eivind A. B. Undheim, Sebastian Senff, Mehdi Mobli, Claire Dauly, Pierre Escoubas, Graham M. Nicholson, Quentin Kaas, Shaodong Guo, Volker Herzig, John S. Mattick, Glenn F. King. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene. Proceedings of the National Academy of Sciences. 2020; 117 (21):11399-11408.

Chicago/Turabian Style

Sandy S. Pineda; Yanni K.-Y. Chin; Eivind A. B. Undheim; Sebastian Senff; Mehdi Mobli; Claire Dauly; Pierre Escoubas; Graham M. Nicholson; Quentin Kaas; Shaodong Guo; Volker Herzig; John S. Mattick; Glenn F. King. 2020. "Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene." Proceedings of the National Academy of Sciences 117, no. 21: 11399-11408.

Review
Published: 09 April 2020 in Marine Drugs
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This review examines the current state of knowledge regarding toxins from anthozoans (sea anemones, coral, zoanthids, corallimorphs, sea pens and tube anemones). We provide an overview of venom from phylum Cnidaria and review the diversity of venom composition between the two major clades (Medusozoa and Anthozoa). We highlight that the functional and ecological context of venom has implications for the temporal and spatial expression of protein and peptide toxins within class Anthozoa. Understanding the nuances in the regulation of venom arsenals has been made possible by recent advances in analytical technologies that allow characterisation of the spatial distributions of toxins. Furthermore, anthozoans are unique in that ecological roles can be assigned using tissue expression data, thereby circumventing some of the challenges related to pharmacological screening.

ACS Style

Lauren M. Ashwood; Raymond S. Norton; Eivind A. B. Undheim; David A. Hurwood; Peter J. Prentis. Characterising Functional Venom Profiles of Anthozoans and Medusozoans within Their Ecological Context. Marine Drugs 2020, 18, 202 .

AMA Style

Lauren M. Ashwood, Raymond S. Norton, Eivind A. B. Undheim, David A. Hurwood, Peter J. Prentis. Characterising Functional Venom Profiles of Anthozoans and Medusozoans within Their Ecological Context. Marine Drugs. 2020; 18 (4):202.

Chicago/Turabian Style

Lauren M. Ashwood; Raymond S. Norton; Eivind A. B. Undheim; David A. Hurwood; Peter J. Prentis. 2020. "Characterising Functional Venom Profiles of Anthozoans and Medusozoans within Their Ecological Context." Marine Drugs 18, no. 4: 202.

Communication
Published: 18 December 2019 in Angewandte Chemie International Edition
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Enzymes are central components of most physiological processes, and are consequently implicated in various pathologies. High‐resolution maps of enzyme activity within tissues therefore represent powerful tools for elucidating enzymatic functions in health and disease. Here, we present a novel mass spectrometry imaging (MSI) method for assaying the spatial distribution of enzymatic activity directly from tissue. MSI analysis of tissue sections exposed to phospholipid substrates produced high‐resolution maps of phospholipase activity and specificity, which could subsequently be compared to histological images of the same section. Functional MSI thus represents a new and generalisable method for imaging biological activity in situ .

ACS Style

Brett R. Hamilton; David L. Marshall; Nicholas R. Casewell; Robert A. Harrison; Stephen J. Blanksby; Eivind Andreas Baste Undheim. Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging. Angewandte Chemie International Edition 2019, 59, 3855 -3858.

AMA Style

Brett R. Hamilton, David L. Marshall, Nicholas R. Casewell, Robert A. Harrison, Stephen J. Blanksby, Eivind Andreas Baste Undheim. Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging. Angewandte Chemie International Edition. 2019; 59 (10):3855-3858.

Chicago/Turabian Style

Brett R. Hamilton; David L. Marshall; Nicholas R. Casewell; Robert A. Harrison; Stephen J. Blanksby; Eivind Andreas Baste Undheim. 2019. "Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging." Angewandte Chemie International Edition 59, no. 10: 3855-3858.

Communication
Published: 18 December 2019 in Angewandte Chemie
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Enzymes are central components of most physiological processes, and are consequently implicated in various pathologies. High‐resolution maps of enzyme activity within tissues therefore represent powerful tools for elucidating enzymatic functions in health and disease. Here, we present a novel mass spectrometry imaging (MSI) method for assaying the spatial distribution of enzymatic activity directly from tissue. MSI analysis of tissue sections exposed to phospholipid substrates produced high‐resolution maps of phospholipase activity and specificity, which could subsequently be compared to histological images of the same section. Functional MSI thus represents a new and generalisable method for imaging biological activity in situ .

ACS Style

Brett R. Hamilton; David L. Marshall; Nicholas R. Casewell; Robert A. Harrison; Stephen J. Blanksby; Eivind Andreas Baste Undheim. Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging. Angewandte Chemie 2019, 132, 3883 -3886.

AMA Style

Brett R. Hamilton, David L. Marshall, Nicholas R. Casewell, Robert A. Harrison, Stephen J. Blanksby, Eivind Andreas Baste Undheim. Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging. Angewandte Chemie. 2019; 132 (10):3883-3886.

Chicago/Turabian Style

Brett R. Hamilton; David L. Marshall; Nicholas R. Casewell; Robert A. Harrison; Stephen J. Blanksby; Eivind Andreas Baste Undheim. 2019. "Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging." Angewandte Chemie 132, no. 10: 3883-3886.

Journal article
Published: 12 December 2019 in Marine Drugs
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Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular scaffolds for inhibitor design. This investigation is a bioprospecting study that aims to isolate and identify protease inhibitors from the cnidarian Actinia tenebrosa. The study isolated two Kunitz-type protease inhibitors with very similar sequences but quite divergent inhibitory potencies when assayed against bovine trypsin, chymostrypsin, and a selection of human sequence-related peptidases. Homology modeling and molecular dynamics simulations of these inhibitors in complex with their targets were carried out and, collectively, these methodologies enabled the definition of a versatile scaffold for inhibitor design. Thermal denaturation studies showed that the inhibitors were remarkably robust. To gain a fine-grained map of the residues responsible for this stability, we conducted in silico alanine scanning and quantified individual residue contributions to the inhibitor’s stability. Sequences of these inhibitors were then used to search for Kunitz homologs in an A. tenebrosa transcriptome library, resulting in the discovery of a further 14 related sequences. Consensus analysis of these variants identified a rich molecular diversity of Kunitz domains and expanded the palette of potential residue substitutions for rational inhibitor design using this domain.

ACS Style

Xingchen Chen; Darren Leahy; Jessica Van Haeften; Perry Hartfield; Peter J. Prentis; Chloé A. Van Der Burg; Joachim M. Surm; Ana Pavasovic; Bruno Madio; Brett R. Hamilton; Glenn F. King; Eivind A. B. Undheim; Maria Brattsand; Jonathan M. Harris. A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa. Marine Drugs 2019, 17, 701 .

AMA Style

Xingchen Chen, Darren Leahy, Jessica Van Haeften, Perry Hartfield, Peter J. Prentis, Chloé A. Van Der Burg, Joachim M. Surm, Ana Pavasovic, Bruno Madio, Brett R. Hamilton, Glenn F. King, Eivind A. B. Undheim, Maria Brattsand, Jonathan M. Harris. A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa. Marine Drugs. 2019; 17 (12):701.

Chicago/Turabian Style

Xingchen Chen; Darren Leahy; Jessica Van Haeften; Perry Hartfield; Peter J. Prentis; Chloé A. Van Der Burg; Joachim M. Surm; Ana Pavasovic; Bruno Madio; Brett R. Hamilton; Glenn F. King; Eivind A. B. Undheim; Maria Brattsand; Jonathan M. Harris. 2019. "A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa." Marine Drugs 17, no. 12: 701.

Journal article
Published: 26 November 2019 in Proceedings of the National Academy of Sciences
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Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find thatKLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.

ACS Style

Nicholas R. Casewell; Daniel Petras; Daren C. Card; Vivek Suranse; Alexis M. Mychajliw; David Richards; Ivan Koludarov; Laura-Oana Albulescu; Julien Slagboom; Benjamin-Florian Hempel; Neville M. Ngum; Rosalind J. Kennerley; Jorge L. Brocca; Gareth Whiteley; Robert A. Harrison; Fiona M. S. Bolton; Jordan Debono; Freek J. Vonk; Jessica Alföldi; Jeremy Johnson; Elinor K. Karlsson; Kerstin Lindblad-Toh; Ian Mellor; Roderich D. Süssmuth; Bryan G. Fry; Sanjaya Kuruppu; Wayne Hodgson; Jeroen Kool; Todd A. Castoe; Ian Barnes; Kartik Sunagar; Eivind A. B. Undheim; Samuel T. Turvey. Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals. Proceedings of the National Academy of Sciences 2019, 116, 25745 -25755.

AMA Style

Nicholas R. Casewell, Daniel Petras, Daren C. Card, Vivek Suranse, Alexis M. Mychajliw, David Richards, Ivan Koludarov, Laura-Oana Albulescu, Julien Slagboom, Benjamin-Florian Hempel, Neville M. Ngum, Rosalind J. Kennerley, Jorge L. Brocca, Gareth Whiteley, Robert A. Harrison, Fiona M. S. Bolton, Jordan Debono, Freek J. Vonk, Jessica Alföldi, Jeremy Johnson, Elinor K. Karlsson, Kerstin Lindblad-Toh, Ian Mellor, Roderich D. Süssmuth, Bryan G. Fry, Sanjaya Kuruppu, Wayne Hodgson, Jeroen Kool, Todd A. Castoe, Ian Barnes, Kartik Sunagar, Eivind A. B. Undheim, Samuel T. Turvey. Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals. Proceedings of the National Academy of Sciences. 2019; 116 (51):25745-25755.

Chicago/Turabian Style

Nicholas R. Casewell; Daniel Petras; Daren C. Card; Vivek Suranse; Alexis M. Mychajliw; David Richards; Ivan Koludarov; Laura-Oana Albulescu; Julien Slagboom; Benjamin-Florian Hempel; Neville M. Ngum; Rosalind J. Kennerley; Jorge L. Brocca; Gareth Whiteley; Robert A. Harrison; Fiona M. S. Bolton; Jordan Debono; Freek J. Vonk; Jessica Alföldi; Jeremy Johnson; Elinor K. Karlsson; Kerstin Lindblad-Toh; Ian Mellor; Roderich D. Süssmuth; Bryan G. Fry; Sanjaya Kuruppu; Wayne Hodgson; Jeroen Kool; Todd A. Castoe; Ian Barnes; Kartik Sunagar; Eivind A. B. Undheim; Samuel T. Turvey. 2019. "Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals." Proceedings of the National Academy of Sciences 116, no. 51: 25745-25755.

Journal article
Published: 18 November 2019 in Toxins
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Assassin bugs (Reduviidae) produce venoms that are insecticidal, and which induce pain in predators, but the composition and function of their individual venom components is poorly understood. We report findings on the venom system of the red-spotted assassin bug Platymeris rhadamanthus, a large species of African origin that is unique in propelling venom as a projectile weapon when threatened. We performed RNA sequencing experiments on venom glands (separate transcriptomes of the posterior main gland, PMG, and the anterior main gland, AMG), and proteomic experiments on venom that was either defensively propelled or collected from the proboscis in response to electrostimulation. We resolved a venom proteome comprising 166 polypeptides. Both defensively propelled venom and most venom samples collected in response to electrostimulation show a protein profile similar to the predicted secretory products of the PMG, with a smaller contribution from the AMG. Pooled venom samples induce calcium influx via membrane lysis when applied to mammalian neuronal cells, consistent with their ability to cause pain when propelled into the eyes or mucus membranes of potential predators. The same venom induces rapid paralysis and death when injected into fruit flies. These data suggest that the cytolytic, insecticidal venom used by reduviids to capture prey is also a highly effective defensive weapon when propelled at predators.

ACS Style

Andrew Walker; Samuel Robinson; Eivind Undheim; Jiayi Jin; Xiao Han; Bryan Fry; Irina Vetter; Glenn King. Missiles of Mass Disruption: Composition and Glandular Origin of Venom Used as a Projectile Defensive Weapon by the Assassin Bug Platymeris rhadamanthus. Toxins 2019, 11, 673 .

AMA Style

Andrew Walker, Samuel Robinson, Eivind Undheim, Jiayi Jin, Xiao Han, Bryan Fry, Irina Vetter, Glenn King. Missiles of Mass Disruption: Composition and Glandular Origin of Venom Used as a Projectile Defensive Weapon by the Assassin Bug Platymeris rhadamanthus. Toxins. 2019; 11 (11):673.

Chicago/Turabian Style

Andrew Walker; Samuel Robinson; Eivind Undheim; Jiayi Jin; Xiao Han; Bryan Fry; Irina Vetter; Glenn King. 2019. "Missiles of Mass Disruption: Composition and Glandular Origin of Venom Used as a Projectile Defensive Weapon by the Assassin Bug Platymeris rhadamanthus." Toxins 11, no. 11: 673.

Review
Published: 14 November 2019 in Toxins
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Venoms are one of the most convergent of animal traits known, and encompass a much greater taxonomic and functional diversity than is commonly appreciated. This knowledge gap limits the potential of venom as a model trait in evolutionary biology. Here, we summarize the taxonomic and functional diversity of animal venoms and relate this to what is known about venom system morphology, venom modulation, and venom pharmacology, with the aim of drawing attention to the importance of these largely neglected aspects of venom research. We find that animals have evolved venoms at least 101 independent times and that venoms play at least 11 distinct ecological roles in addition to predation, defense, and feeding. Comparisons of different venom systems suggest that morphology strongly influences how venoms achieve these functions, and hence is an important consideration for understanding the molecular evolution of venoms and their toxins. Our findings also highlight the need for more holistic studies of venom systems and the toxins they contain. Greater knowledge of behavior, morphology, and ecologically relevant toxin pharmacology will improve our understanding of the evolution of venoms and their toxins, and likely facilitate exploration of their potential as sources of molecular tools and therapeutic and agrochemical lead compounds.

ACS Style

Vanessa Schendel; Lachlan D. Rash; Ronald A. Jenner; Eivind A. B. Undheim. The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution. Toxins 2019, 11, 666 .

AMA Style

Vanessa Schendel, Lachlan D. Rash, Ronald A. Jenner, Eivind A. B. Undheim. The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution. Toxins. 2019; 11 (11):666.

Chicago/Turabian Style

Vanessa Schendel; Lachlan D. Rash; Ronald A. Jenner; Eivind A. B. Undheim. 2019. "The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution." Toxins 11, no. 11: 666.

Comparative study
Published: 08 August 2019 in Molecular Biology and Evolution
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Centipedes are among the most ancient groups of venomous predatory arthropods. Extant species belong to five orders, but our understanding of the composition and evolution of centipede venoms is based almost exclusively on one order, Scolopendromorpha. To gain a broader and less biased understanding we performed a comparative proteotranscriptomic analysis of centipede venoms from all five orders, including the first venom profiles for the orders Lithobiomorpha, Craterostigmomorpha, and Geophilomorpha. Our results reveal an astonishing structural diversity of venom components, with 93 phylogenetically distinct protein and peptide families. Proteomically-annotated gene trees of these putative toxin families show that centipede venom composition is highly dynamic across macroevolutionary timescales, with numerous gene duplications as well as functional recruitments and losses of toxin gene families. Strikingly, not a single family is found in the venoms of representatives of all five orders, with 67 families being unique for single orders. Ancestral state reconstructions reveal that centipede venom originated as a simple cocktail comprising just four toxin families, with very little compositional evolution happening during the approximately 50 My before the living orders had diverged. Venom complexity then increased in parallel within the orders, with scolopendromorphs evolving particularly complex venoms. Our results show that even venoms composed of toxins evolving under the strong constraint of negative selection can have striking evolutionary plasticity on the compositional level. We show that the functional recruitments and losses of toxin families that shape centipede venom arsenals are not concentrated early in their evolutionary history, but happen frequently throughout.

ACS Style

Ronald A Jenner; Bjoern Marcus von Reumont; Lahcen Campbell; Eivind A B Undheim. Parallel Evolution of Complex Centipede Venoms Revealed by Comparative Proteotranscriptomic Analyses. Molecular Biology and Evolution 2019, 36, 2748 -2763.

AMA Style

Ronald A Jenner, Bjoern Marcus von Reumont, Lahcen Campbell, Eivind A B Undheim. Parallel Evolution of Complex Centipede Venoms Revealed by Comparative Proteotranscriptomic Analyses. Molecular Biology and Evolution. 2019; 36 (12):2748-2763.

Chicago/Turabian Style

Ronald A Jenner; Bjoern Marcus von Reumont; Lahcen Campbell; Eivind A B Undheim. 2019. "Parallel Evolution of Complex Centipede Venoms Revealed by Comparative Proteotranscriptomic Analyses." Molecular Biology and Evolution 36, no. 12: 2748-2763.

Review
Published: 01 June 2019 in Marine Drugs
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Sea anemones produce venoms of exceptional molecular diversity, with at least 17 different molecular scaffolds reported to date. These venom components have traditionally been classified according to pharmacological activity and amino acid sequence. However, this classification system suffers from vulnerabilities due to functional convergence and functional promiscuity. Furthermore, for most known sea anemone toxins, the exact receptors they target are either unknown, or at best incomplete. In this review, we first provide an overview of the sea anemone venom system and then focus on the venom components. We have organised the venom components by distinguishing firstly between proteins and non-proteinaceous compounds, secondly between enzymes and other proteins without enzymatic activity, then according to the structural scaffold, and finally according to molecular target.

ACS Style

Bruno Madio; Glenn F. King; Eivind A. B. Undheim. Sea Anemone Toxins: A Structural Overview. Marine Drugs 2019, 17, 325 .

AMA Style

Bruno Madio, Glenn F. King, Eivind A. B. Undheim. Sea Anemone Toxins: A Structural Overview. Marine Drugs. 2019; 17 (6):325.

Chicago/Turabian Style

Bruno Madio; Glenn F. King; Eivind A. B. Undheim. 2019. "Sea Anemone Toxins: A Structural Overview." Marine Drugs 17, no. 6: 325.

Article
Published: 01 February 2019 in Structure
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Summary Disulfide-rich peptides (DRPs) play diverse physiological roles and have emerged as attractive sources of pharmacological tools and drug leads. Here we describe the 3D structure of a centipede venom peptide, U-SLPTX15-Sm2a, whose family defines a unique class of one of the most widespread DRP folds known, the cystine-stabilized α/β fold (CSαβ). This class, which we have named the two-disulfide CSαβ fold (2ds-CSαβ), contains only two internal disulfide bonds as opposed to at least three in all other confirmed CSαβ peptides, and constitutes one of the major neurotoxic peptide families in centipede venoms. We show the 2ds-CSαβ is widely distributed outside centipedes and is likely an ancient fold predating the split between prokaryotes and eukaryotes. Our results provide insights into the ancient evolutionary history of a widespread DRP fold and highlight the usefulness of 3D structures as evolutionary tools.

ACS Style

Thomas S. Dash; Thomas Shafee; Peta J. Harvey; Chuchu Zhang; Steve Peigneur; Jennifer R. Deuis; Irina Vetter; Jan Tytgat; Marilyn A. Anderson; David J. Craik; Thomas Durek; Eivind A.B. Undheim. A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins. Structure 2019, 27, 315 -326.e7.

AMA Style

Thomas S. Dash, Thomas Shafee, Peta J. Harvey, Chuchu Zhang, Steve Peigneur, Jennifer R. Deuis, Irina Vetter, Jan Tytgat, Marilyn A. Anderson, David J. Craik, Thomas Durek, Eivind A.B. Undheim. A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins. Structure. 2019; 27 (2):315-326.e7.

Chicago/Turabian Style

Thomas S. Dash; Thomas Shafee; Peta J. Harvey; Chuchu Zhang; Steve Peigneur; Jennifer R. Deuis; Irina Vetter; Jan Tytgat; Marilyn A. Anderson; David J. Craik; Thomas Durek; Eivind A.B. Undheim. 2019. "A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins." Structure 27, no. 2: 315-326.e7.

Conference abstract
Published: 30 January 2019 in Toxicon
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Eivind A.B. Undheim; David Richards; Neville Ngum; David Tooth; Dong-Hyun Kim; Ian Mellor. When sex matters: Dramatic sexual dimorphism in the venom and venom system of the centipede Scolopendra hardwickei. Toxicon 2019, 158, S5 .

AMA Style

Eivind A.B. Undheim, David Richards, Neville Ngum, David Tooth, Dong-Hyun Kim, Ian Mellor. When sex matters: Dramatic sexual dimorphism in the venom and venom system of the centipede Scolopendra hardwickei. Toxicon. 2019; 158 ():S5.

Chicago/Turabian Style

Eivind A.B. Undheim; David Richards; Neville Ngum; David Tooth; Dong-Hyun Kim; Ian Mellor. 2019. "When sex matters: Dramatic sexual dimorphism in the venom and venom system of the centipede Scolopendra hardwickei." Toxicon 158, no. : S5.

Short communication
Published: 02 January 2019 in Toxicon: X
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The rate of discovery of new spider species greatly exceeds the rate of spider venom characterisation, leading to an increasing number of species with unstudied venoms. However, recent advances in proteomics and genomics that enable the study of venoms from smaller species has expanded the accessible taxonomic range. Thus, although the number of unstudied spider venoms is likely to further increase, future research should focus on the characterisation of venoms and toxins from previously unstudied spider families.

ACS Style

Volker Herzig; Glenn F. King; Eivind A.B. Undheim. Can we resolve the taxonomic bias in spider venom research? Toxicon: X 2019, 1, 100005 .

AMA Style

Volker Herzig, Glenn F. King, Eivind A.B. Undheim. Can we resolve the taxonomic bias in spider venom research? Toxicon: X. 2019; 1 ():100005.

Chicago/Turabian Style

Volker Herzig; Glenn F. King; Eivind A.B. Undheim. 2019. "Can we resolve the taxonomic bias in spider venom research?" Toxicon: X 1, no. : 100005.

Original research article
Published: 20 November 2018 in Frontiers in Pharmacology
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Peptide toxins isolated from animal venom secretions have proven to be useful pharmacological tools for probing the structure and function of a number of molecular receptors. Their molecular structures are stabilized by posttranslational formation of multiple disulfide bonds formed between sidechain thiols of cysteine residues, resulting in high thermal and chemical stability. Many of these peptides have been found to be potent modulators of ion channels, making them particularly influential in this field. Recently, several peptide toxins have been described that have an unusual tandem repeat organization, while also eliciting a unique pharmacological response toward ion channels. Most of these are two-domain peptide toxins from spider venoms, such as the double-knot toxin (DkTx), isolated from the Earth Tiger tarantula (Haplopelma schmidti). The unusual pharmacology of DkTx is its high avidity for its receptor (TRPV1), a property that has been attributed to a bivalent mode-of-action. DkTx has subsequently proven a powerful tool for elucidating the structural basis for the function of the TRPV1 channel. Interestingly, all tandem repeat peptides functionally characterized to date share this high avidity to their respective binding targets, suggesting they comprise an unrecognized structural class of peptides with unique structural features that result in a characteristic set of pharmacological properties. In this article, we explore the prevalence of this emerging class of peptides, which we have named Secreted, Cysteine-rich REpeat Peptides, or “SCREPs.” To achieve this, we have employed data mining techniques to extract SCREP-like sequences from the UniProtKB database, yielding approximately sixty thousand candidates. These results indicate that SCREPs exist within a diverse range of species with greatly varying sizes and predicted fold types, and likely include peptides with novel structures and unique modes of action. We present our approach to mining this database for discovery of novel ion-channel modulators and discuss a number of “hits” as promising leads for further investigation. Our database of SCREPs thus constitutes a novel resource for biodiscovery and highlights the value of a data-driven approach to the identification of new bioactive pharmacological tools and therapeutic lead molecules.

ACS Style

Michael Maxwell; Eivind A. B. Undheim; Mehdi Mobli. Secreted Cysteine-Rich Repeat Proteins “SCREPs”: A Novel Multi-Domain Architecture. Frontiers in Pharmacology 2018, 9, 1 .

AMA Style

Michael Maxwell, Eivind A. B. Undheim, Mehdi Mobli. Secreted Cysteine-Rich Repeat Proteins “SCREPs”: A Novel Multi-Domain Architecture. Frontiers in Pharmacology. 2018; 9 ():1.

Chicago/Turabian Style

Michael Maxwell; Eivind A. B. Undheim; Mehdi Mobli. 2018. "Secreted Cysteine-Rich Repeat Proteins “SCREPs”: A Novel Multi-Domain Architecture." Frontiers in Pharmacology 9, no. : 1.

Research article
Published: 12 September 2018 in Science Advances
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Ants (Hymenoptera: Formicidae) are diverse and ubiquitous, and their ability to sting is familiar to many of us. However, their venoms remain largely unstudied. We provide the first comprehensive characterization of a polypeptidic ant venom, that of the giant red bull ant, Myrmecia gulosa. We reveal a suite of novel peptides with a range of posttranslational modifications, including disulfide bond formation, dimerization, and glycosylation. One venom peptide has sequence features consistent with an epidermal growth factor fold, while the remaining peptides have features suggestive of a capacity to form amphipathic helices. We show that these peptides are derived from what appears to be a single, pharmacologically diverse, gene superfamily (aculeatoxins) that includes most venom peptides previously reported from the aculeate Hymenoptera. Two aculeatoxins purified from the venom were found to be capable of activating mammalian sensory neurons, consistent with the capacity to produce pain but via distinct mechanisms of action. Further investigation of the major venom peptide MIITX1-Mg1a revealed that it can also incapacitate arthropods, indicative of dual utility in both defense and predation. MIITX1-Mg1a accomplishes these functions by generating a leak in membrane ion conductance, which alters membrane potential and triggers neuronal depolarization. Our results provide the first insights into the evolution of the major toxin gene superfamily of the aculeate Hymenoptera and provide a new paradigm in the functional evolution of toxins from animal venoms.

ACS Style

Samuel D. Robinson; Alexander Mueller; Daniel Clayton; Hana Starobova; Brett R. Hamilton; Richard J. Payne; Irina Vetter; Glenn F. King; Eivind A. B. Undheim. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 2018, 4, eaau4640 .

AMA Style

Samuel D. Robinson, Alexander Mueller, Daniel Clayton, Hana Starobova, Brett R. Hamilton, Richard J. Payne, Irina Vetter, Glenn F. King, Eivind A. B. Undheim. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances. 2018; 4 (9):eaau4640.

Chicago/Turabian Style

Samuel D. Robinson; Alexander Mueller; Daniel Clayton; Hana Starobova; Brett R. Hamilton; Richard J. Payne; Irina Vetter; Glenn F. King; Eivind A. B. Undheim. 2018. "A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family." Science Advances 4, no. 9: eaau4640.