ORCID Profile
0000-0002-8035-4719
Current Organisation
Liverpool School of Tropical Medicine
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Genomics | Molecular Evolution | Systems Biology | Genetics
Publisher: Public Library of Science (PLoS)
Date: 24-06-2020
Publisher: Public Library of Science (PLoS)
Date: 29-11-2013
Publisher: Elsevier BV
Date: 03-2013
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.JPROT.2014.01.004
Abstract: For over a century, venom s les from wild snakes have been collected and stored around the world. However, the quality of storage conditions for "vintage" venoms has rarely been assessed. The goal of this study was to determine whether such historical venom s les are still biochemically and pharmacologically viable for research purposes, or if new s le efforts are needed. In total, 52 s les spanning 5 genera and 13 species with regional variants of some species (e.g., 14 different populations of Notechis scutatus) were analysed by a combined proteomic and pharmacological approach to determine protein structural stability and bioactivity. When venoms were not exposed to air during storage, the proteomic results were virtually indistinguishable from that of fresh venom and bioactivity was equivalent or only slightly reduced. By contrast, a s le of Acanthophis antarcticus venom that was exposed to air (due to a loss of integrity of the rubber stopper) suffered significant degradation as evidenced by the proteomics profile. Interestingly, the neurotoxicity of this s le was nearly the same as fresh venom, indicating that degradation may have occurred in the free N- or C-terminus chains of the proteins, rather than at the tips of loops where the functional residues are located. These results suggest that these and other vintage venom collections may be of continuing value in toxin research. This is particularly important as many snake species worldwide are declining due to habitat destruction or modification. For some venoms (such as N. scutatus from Babel Island, Flinders Island, King Island and St. Francis Island) these were the first analyses ever conducted and these vintage s les may represent the only venom ever collected from these unique island forms of tiger snakes. Such vintage venoms may therefore represent the last remaining stocks of some local populations and thus are precious resources. These venoms also have significant historical value as the Oxyuranus venoms analysed include s les from the first coastal taipan (Oxyuranus scutellatus) collected for antivenom production (the snake that killed the collector Kevin Budden), as well as s les from the first Oxyuranus microlepidotus specimen collected after the species' rediscovery in 1976. These results demonstrate that with proper storage techniques, venom s les can retain structural and pharmacological stability. This article is part of a Special Issue entitled: Proteomics of non-model organisms.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.TOXICON.2012.02.013
Abstract: The evolutionary origin and ersification of the reptilian venom system is described. The resolution of higher-order molecular phylogenetics has clearly established that a venom system is ancestral to snakes. The ersification of the venom system within lizards is discussed, as is the role of venom delivery in the behavioural ecology of these taxa (particularly Varanus komodoensis). The more extensive ersification of the venom system in snakes is summarised, including its loss in some clades. Finally, we discuss the contentious issue of a definition for "venom", supporting an evolutionary definition that recognises the homology of both the venom delivery systems and the toxins themselves.
Publisher: Proceedings of the National Academy of Sciences
Date: 26-11-2019
Abstract: 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 that KLK1 s have been independently coopted into the venom of shrews and solenodons following their ergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking ex le of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.
Publisher: Elsevier BV
Date: 05-2017
Publisher: Wiley
Date: 26-03-2018
DOI: 10.1111/JHN.12550
Abstract: Little is known about the adequacy of nutrient intakes and the overall diet quality of Indigenous Australian pregnant women. The aim of this cross-sectional study was to assess nutrient sufficiency and diet quality, as measured using the Australian Recommended Food Score (ARFS), in pregnant women from the Gomeroi gaaynggal cohort (n = 58). Maternal dietary intake during pregnancy was assessed using the Australian Eating Survey Food Frequency Questionnaire, which was self-administered in the third trimester. Diet quality was determined using the ARFS. Food group servings and nutrient intakes were compared to the Australian Guide to Health Eating (AGHE) and Australian Nutrient Reference Values (NRVs). The current analysis examined the adequacy of usual intakes from food sources only, excluding supplements. None of the women met all AGHE daily food group serving recommendations. The highest alignment rates were for dairy (33%), meat/alternatives (31%) and vegetables (29.3%). Almost 93% of participants exceeded the recommended intake of energy-dense, nutrient-poor foods and percentage energy from saturated fat was high (15%). Of the five key nutrients for optimal reproductive health (folate, iron, calcium, zinc and fibre), the nutrients with the highest percentage of pregnant women achieving the NRVs were zinc (77.6%) and folate (68.9%), whereas iron was the lowest. Only one person achieved all NRVs (folate, iron, calcium, zinc and fibre) important in pregnancy. The median ARFS was 28 points (maximum of 73). Although the small cohort limits the generalisability of the findings of the present study, the data obtained indicate that the diets of these Indigenous pregnant women are inadequate. Therefore, strategies aiming to optimise nutrient intakes of Indigenous pregnant women are needed urgently.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JPROT.2014.09.003
Abstract: Venoms of the viperid sister genera Eristicophis and Pseudocerastes are poorly studied despite their anecdotal reputation for producing severe or even lethal envenomations. This is due in part to the remote and politically unstable regions that they occupy. All species contained are sit and wait ambush feeders. Thus, this study examined their venoms through proteomics techniques in order to establish if this feeding ecology, and putatively low levels of gene flow, have resulted in significant variations in venom profile. The techniques indeed revealed extreme venom variation. This has immediate implications as only one antivenom is made (using the venom of Pseudocerastes persicus) yet the proteomic variation suggests that it would be of only limited use for the other species, even the sister species Pseudocerastes fieldi. The high degree of variation however also points toward these species being rich resources for novel compounds which may have use as lead molecules in drug design and development. These results show extreme venom variation between these closely related snakes. These results have direct implications for the treatment of the envenomed patient.
Publisher: MDPI AG
Date: 18-03-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-01-2021
Abstract: Venom in snakes is largely used to subdue and/or kill prey, and most venoms have clear actions that facilitate death or paralysis. In one group of snakes, however, venom has evolved and shifted from predation to protection. Specifically, in three different lineages of “spitting” snakes, venom is used to deter predators. Kazandjian et al. show that similar adaptions have occurred within these lineages that transform cytotoxic components into a mixture that acts on mammalian sensory neurons and causes pain. The authors argue that increased predation on these lineages led to similar shifts in venom function. Science , this issue p. 386
Publisher: MDPI AG
Date: 02-02-2021
Abstract: Snakes of the genera Pseudocerastes and Eristicophis (Viperidae: Viperinae) are known as the desert vipers due to their association with the arid environments of the Middle East. These species have received limited research attention and little is known about their venom or ecology. In this study, a comprehensive analysis of desert viper venoms was conducted by visualising the venom proteomes via gel electrophoresis and assessing the crude venoms for their cytotoxic, haemotoxic, and neurotoxic properties. Plasmas sourced from human, toad, and chicken were used as models to assess possible prey-linked venom activity. The venoms demonstrated substantial ergence in composition and bioactivity across all experiments. Pseudocerastes urarachnoides venom activated human coagulation factors X and prothrombin and demonstrated potent procoagulant activity in human, toad, and chicken plasmas, in stark contrast to the potent neurotoxic venom of P. fieldi. The venom of E. macmahonii also induced coagulation, though this did not appear to be via the activation of factor X or prothrombin. The coagulant properties of P. fieldi and P. persicus venoms varied among plasmas, demonstrating strong anticoagulant activity in the hibian and human plasmas but no significant effect in that of bird. This is conjectured to reflect prey-specific toxin activity, though further ecological studies are required to confirm any dietary associations. This study reinforces the notion that phylogenetic relatedness of snakes cannot readily predict venom protein composition or function. The significant venom variation between these species raises serious concerns regarding antivenom paraspecificity. Future assessment of antivenom is crucial.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-09-2015
Abstract: Convergence has strong bearing on the fundamental debate about whether evolution is stochastic and unpredictable or subject to constraints. Here we show that, in certain circumstances, evolution can be highly predictable. We demonstrate that several lineages of insects, hibians, reptiles, and mammals have utilized the same molecular solution, via the process of convergence, to evolve resistance to toxic cardiac glycosides produced defensively by plants and bufonid toads. The repeatability of this process across the animal kingdom demonstrates that evolution can be constrained to proceed along highly predictable pathways at molecular and functional levels. Our study has important implications for conservation biology by providing a predictive framework for assessing the vulnerability of native fauna to the introduction of invasive toxic toads.
Publisher: Oxford University Press (OUP)
Date: 16-08-2016
Abstract: Much of what is known about the molecular evolution of vertebrate vision comes from studies of mammals, birds and fish. Reptiles (especially snakes) have barely been s led in previous studies despite their exceptional ersity of retinal photoreceptor complements. Here, we analyze opsin gene sequences and ocular media transmission for up to 69 species to investigate snake visual evolution. Most snakes express three visual opsin genes (rh1, sws1, and lws). These opsin genes (especially rh1 and sws1) have undergone much evolutionary change, including modifications of amino acid residues at sites of known importance for spectral tuning, with several tuning site combinations unknown elsewhere among vertebrates. These changes are particularly common among dipsadine and colubrine "higher" snakes. All three opsin genes are inferred to be under purifying selection, though dN/dS varies with respect to some lineages, ecologies, and retinal anatomy. Positive selection was inferred at multiple sites in all three opsins, these being concentrated in transmembrane domains and thus likely to have a substantial effect on spectral tuning and other aspects of opsin function. Snake lenses vary substantially in their spectral transmission. Snakes active at night and some of those active by day have very transmissive lenses, whereas some primarily diurnal species cut out shorter wavelengths (including UVA). In terms of retinal anatomy, lens transmission, visual pigment spectral tuning and opsin gene evolution the visual system of snakes is exceptionally erse compared with all other extant tetrapod orders.
Publisher: Proceedings of the National Academy of Sciences
Date: 02-12-2013
Abstract: Snake venoms are toxic protein cocktails used for prey capture. To investigate the evolution of these complex biological weapon systems, we sequenced the genome of a venomous snake, the king cobra, and assessed the composition of venom gland expressed genes, small RNAs, and secreted venom proteins. We show that regulatory components of the venom secretory system may have evolved from a pancreatic origin and that venom toxin genes were co-opted by distinct genomic mechanisms. After co-option, toxin genes important for prey capture have massively expanded by gene duplication and evolved under positive selection, resulting in protein neofunctionalization. This erse and dramatic venom-related genomic response seemingly occurs in response to a coevolutionary arms race between venomous snakes and their prey.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.TOXLET.2017.08.020
Abstract: Saw-scaled vipers (genus Echis) are one of the leading causes of snakebite morbidity and mortality in parts of Sub-Saharan Africa, the Middle East, and vast regions of Asia, constituting a public health burden exceeding that of almost any other snake genus globally. Venom-induced consumption coagulopathy, owing to the action of potent procoagulant toxins, is one of the most relevant clinical manifestations of envenomings by Echis spp. Clinical experience and prior studies examining a limited range of venoms and restricted antivenoms have demonstrated for some antivenoms an extreme lack of antivenom cross-reactivity between different species of this genus, sometimes resulting in catastrophic treatment failure. This study undertook the most comprehensive testing of Echis venom effects upon the coagulation of human plasma, and also the broadest examination of antivenom potency and cross-reactivity, to-date. 10 Echis species opulations and four antivenoms (two African, two Asian) were studied. The results indicate that the venoms are, in general, potently procoagulant but that the relative dependence on calcium or phospholipid cofactors is highly variable. Additionally, three out of the four antivenoms tested demonstrated only a very narrow taxonomic range of effectiveness in preventing coagulopathy, with only the SAIMR antivenom displaying significant levels of cross-reactivity. These results were in conflict with previous studies using prolonged preincubation of antivenom with venom to suggest effective cross-reactivity levels for the ICP Echi-Tab antivenom. These findings both inform upon potential clinical effects of envenomation in humans and highlight the extreme limitations of available treatment. It is hoped that this will spur efforts into the development of antivenoms with more comprehensive coverage for bites not only from wild snakes but also from specimens widely kept in zoological collections.
Publisher: MDPI AG
Date: 27-06-2021
DOI: 10.3390/IJMS22136896
Abstract: Venoms are a rich source of potential lead compounds for drug discovery, and descriptive studies of venom form the first phase of the biodiscovery process. In this study, we investigated the pharmacological potential of crude Pseudocerastes and Eristicophis snake venoms in haematological disorders and cancer treatment. We assessed their antithrombotic potential using fibrinogen thromboelastography, fibrinogen gels with and without protease inhibitors, and colourimetric fibrinolysis assays. These assays indicated that the anticoagulant properties of the venoms are likely induced by the hydrolysis of phospholipids and by selective fibrinogenolysis. Furthermore, while most fibrinogenolysis occurred by the direct activity of snake venom metalloproteases and serine proteases, modest evidence indicated that fibrinogenolytic activity may also be mediated by selective venom phospholipases and an inhibitory venom-derived serine protease. We also found that the Pseudocerastes venoms significantly reduced the viability of human melanoma (MM96L) cells by more than 80%, while it had almost no effect on the healthy neonatal foreskin fibroblasts (NFF) as determined by viability assays. The bioactive properties of these venoms suggest that they contain a number of toxins suitable for downstream pharmacological development as candidates for antithrombotic or anticancer agents.
Publisher: Elsevier BV
Date: 03-2013
Publisher: MDPI AG
Date: 15-12-2021
Abstract: The snake genus Daboia (Viperidae: Viperinae Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell’s vipers D. russelii and D. siamensis, found in Asia. Russell’s vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell’s vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell’s vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.
Publisher: MDPI AG
Date: 19-05-2017
Publisher: Wiley
Date: 23-01-2020
Publisher: Oxford University Press (OUP)
Date: 17-11-2021
DOI: 10.1093/GBE/EVAB253
Abstract: Molecular genetic data have recently been incorporated in attempts to reconstruct the ecology of the ancestral snake, though this has been limited by a paucity of data for one of the two main extant snake taxa, the highly fossorial Scolecophidia. Here we present and analyze vision genes from the first eye-transcriptomic and genome-wide data for Scolecophidia, for Anilios bicolor, and A. bituberculatus, respectively. We also present immunohistochemistry data for retinal anatomy and visual opsin-gene expression in Anilios. Analyzed in the context of 19 lepidosaurian genomes and 12 eye transcriptomes, the new genome-wide and transcriptomic data provide evidence for a much more reduced visual system in Anilios than in non-scolecophidian (=alethinophidian) snakes and in lizards. In Anilios, there is no evidence of the presence of 7 of the 12 genes associated with alethinophidian photopic (cone) phototransduction. This indicates extensive gene loss and many of these candidate gene losses occur also in highly fossorial mammals with reduced vision. Although recent phylogenetic studies have found evidence for scolecophidian paraphyly, the loss in Anilios of visual genes that are present in alethinophidians implies that the ancestral snake had a better-developed visual system than is known for any extant scolecophidian.
Publisher: Wiley
Date: 23-01-2020
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.JPROT.2014.06.004
Abstract: Fish venoms remain almost completely unstudied despite the large number of species. In part this is due to the inherent nature of fish venoms, in that they are highly sensitive to heat, pH, lyophilisation, storage and repeated freeze-thawing. They are also heavily contaminated with mucus, which makes proteomic study difficult. Here we describe a novel protein-handling protocol to remove mucus contamination, utilising ammonium sulphate and acetone precipitation. We validated this approach using barb venom gland tissue protein extract from the blue-spotted stingray Neotrygon kuhlii. We analysed the protein extract using 1D and 2D gels with LC-MS/MS sequencing. Protein annotation was underpinned by a venom gland transcriptome. The composition of our N. kuhlii venom s le revealed a variety of protein types that are completely novel to animal venom systems. Notably, none of the detected proteins exhibited similarity to the few toxin components previously characterised from fish venoms, including those found in other stingrays. Putative venom toxins identified here included cystatin, peroxiredoxin and galectin. Our study represents the first combined survey of gene and protein composition from the venom apparatus of any fish and our novel protein handling method will aid the future characterisation of toxins from other unstudied venomous fish lineages. These results show an efficient manner for removing mucus from fish venoms. These results are the first insights into the evolution of proteins present on stingrayvenom barbs.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 03-2022
End Date: 03-2025
Amount: $528,000.00
Funder: Australian Research Council
View Funded Activity