Simon C Wagstaff's research while affiliated with Liverpool School of Tropical Medicine and other places

Publications (101)

Article
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Significance Lymphatic filariasis caused by Wuchereria bancrofti , Brugia malayi , and Brugia timori affects 51 million people, leading to severe physical and mental disabilities. A mutualistic symbiosis between these filarial nematodes and Wolbachia bacteria has been exploited as a new curative treatment. Epidemiological modeling of anti- Wolbachi...
Article
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Wolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has recently been reported to be present in Anopheles (An.) species. In wild populations of the An. gambiae complex, the primary vectors of Plasmodium malaria in Sub-Saharan Africa,Wolbachia DNA sequences at low density and infection frequencies have been detecte...
Article
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Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populati...
Article
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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 sp...
Preprint
Full-text available
Wolbachia , a widespread bacterium that can reduce pathogen transmission in mosquitoes, has been detected within populations of Anopheles (An.) malaria vectors. In the An. gambiae complex, the primary vectors in Sub-Saharan Africa, Wolbachia strains are at low density and infection frequencies in wild populations. PCR-independent evidence is requir...
Preprint
Full-text available
Convergent evolution provides unparalleled insights into the selective drivers underlying evolutionary change. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of spitting cobras have independently evolved the ability to use venom as a defensive projectile. Using gene, protein and...
Preprint
Full-text available
Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce insect p...
Article
Full-text available
Skin snip evaluation for onchocerciasis has insufficient sensitivity when skin microfilarial (mf) densities are low, such as following ivermectin treatment. Mf density is suitable for assessing microfilaricidal efficacy but only serves as an indirect indicator of macrofilaricidal activity. We assessed circulating nucleic acids from Onchocerca volvu...
Article
Full-text available
Convergent evolution provides unparalleled insights into the selective drivers underlying evolutionary change. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of spitting cobras have independently evolved the ability to use venom as a defensive projectile. Using gene, protein and...
Article
The asp viper Vipera aspis aspis is a venomous snake found in France, and despite its medical importance, the complete toxin repertoire produced is unknown. Here, we used a venomics approach to decipher the composition of its venom. Transcriptomic analysis revealed 80 venom-annotated sequences grouped into 16 gene families. Among the most represent...
Article
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IR-TEx is an application written in Shiny (an R package) that allows exploration of the expression of (as well as assigning functions to) transcripts whose expression is associated with insecticide resistance phenotypes in Anopheles gambiae mosquitoes. The application can be used online or downloaded and used locally by anyone. The local applicatio...
Article
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Snakebite is a neglected tropical disease that causes 138,000 deaths each year. Neurotoxic snake venoms contain small neurotoxins, including three-finger toxins (3FTxs), which can cause rapid paralysis in snakebite victims by blocking postsynaptic transmission via nicotinic acetylcholine receptors (nAChRs). These toxins are typically weakly immunog...
Article
We report on the variable venom composition of a population of the Caucasus viper (Vipera kaznakovi) in Northeastern Turkey. We applied a combination of venom gland transcriptomics, and de-complexing bottom-up and top-down venomics. In contrast to sole bottom-up venomics approaches and gel or chromatography based venom comparison, our combined appr...
Preprint
Full-text available
We report on the variable venom composition of a population of the Caucasus viper ( Vipera kaznakovi ) in Northeastern Turkey. We applied a combination of venom gland transcriptomics, as well as de-complexing bottom-up and top-down venomics, enabling the comparison of the venom proteomes from multiple individuals. In total, we identified peptides a...
Article
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Increasing insecticide resistance in malaria-transmitting vectors represents a public health threat, but underlying mechanisms are poorly understood. Here, a data integration approach is used to analyse transcriptomic data from comparisons of insecticide resistant and susceptible Anopheles populations from disparate geographical regions across the...
Article
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While envenoming by the southern African shield-nosed or coral snakes (genus Aspidelaps) has caused fatalities, bites are uncommon. Consequently, this venom is not used in the mixture of snake venoms used to immunise horses for the manufacture of regional SAIMR (South African Institute for Medical Research) polyvalent antivenom. Aspidelaps species...
Article
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Background: To understand more about changes to the molecular components that occur when host endothelium interacts with Plasmodium falciparum-infected erythrocytes, a combined technique of protein separation (1D Blue-Native electrophoresis) and mass spectrometry of infected erythrocytes with endothelial cells (EC) in a co-culture system has been...
Article
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Background Malaria control in Africa is dependent upon the use insecticides but intensive use of a limited number of chemicals has led to resistance in mosquito populations. Increased production of enzymes that detoxify insecticides is one of the most potent resistance mechanisms. Several metabolic enzymes have been implicated in insecticide resist...
Article
Three aspartic proteases (SVAPs) have been isolated from venom of the saw-scaled viper, Echis ocellatus. In confirmation of prior transcriptomic predictions, all three forms match to sequences of either of the two SVAP transcripts (EOC00051 and EOC00123), have a molecular weight of 42 kDa and possess a single N-glycan. The SVAPs act in a renin-like...
Article
Graphical Abstract Highlights d Fangblennies evolved venom glands after the origin of their canine delivery system d The venom contains toxins that have evolved convergently in other venomous lineages d The defensive venom is multifunctional and exerts potent hypotensive effects d Venom appears to have stimulated the evolution of numerous mimetic r...
Data
MS/MS identification and quantification of the boomslang (Dispholidus typus) venom proteins separated by RP-HPLC and SDS-PAGE as in Fig. 2.
Article
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Background: Non-front-fanged colubroid snakes comprise about two-thirds of extant ophidian species. The medical significance of the majority of these snakes is unknown, but at least five species have caused life-threatening or fatal human envenomings. However, the venoms of only a small number of species have been explored. Methods: A combined v...
Article
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Background: Snake venoms contain many proteinaceous toxins that can cause severe pathology and mortality in snakebite victims. Interestingly, mRNA encoding such toxins can be recovered directly from venom, although yields are low and quality is unknown. It also remains unclear whether such RNA contains information about toxin isoforms and whether...
Data
Primers for elapid PLA2 (A), KSPI (B), CTL (C) and SVMP (D). (PDF)
Data
Multiple sequence alignments for PLA2 (A), KSPI (B), CTL (C) and SVMP (D) amino acid sequences translated from transcripts isolated from the VTRZ of several Elapidae species: A. s. intermedius, A. l. cowlesi, A. l. lubricus and N. kaouthia. (PDF)
Article
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Cnidarian venom research has lagged behind other toxinological fields due to technical difficulties in recovery of the complex venom from the microscopic nematocysts. Here we report a newly developed rapid, repeatable and cost effective technique of venom preparation, using ethanol to induce nematocyst discharge and to recover venom contents in one...
Article
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Background Within many research areas, such as transcriptomics, the millions of short DNA fragments (reads) produced by current sequencing platforms need to be assembled into transcript sequences before they can be utilized. Despite recent advances in assembly software, creating such transcripts from read data harboring isoform variation remains ch...
Article
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Background The elevated expression of enzymes with insecticide metabolism activity can lead to high levels of insecticide resistance in the malaria vector, Anopheles gambiae. In this study, adult female mosquitoes from an insecticide susceptible and resistant strain were dissected into four different body parts. RNA from each of these samples was...
Article
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Significance The toxic composition of snake venom varies between species. Such variation can have major medical implications for the treatment of human snakebite victims. Venom variation is largely attributed to differences in toxin-encoding genes present in the genome or venom gland of snakes. Here, we demonstrate that mechanisms affecting the tra...
Data
Optimisation of venom quantitative PCR. Representative standard curves for snake venom metalloproteinase (SVMP) and C-type lectin (CTL) (1Ai and Aii) show high efficiency amplification of 94.0 and 96.6% respectively. Representative melt curves for SVMP and CTL amplicons showing a single melt peak indicating a single specific amplicon (1Bi and Bii)....
Data
Raw data following gene expression analysis by quantitative PCR. Gene expression analysis conducted using the BioRad CFX manager software. Relative gene expression was calculated from the cycle time (Ct value) using the ΔΔCt method. Expression profiles for all individual specimens in the study are shown illustrating fold changes in the expression o...
Data
Minimum information for Publication of Quantitative Real-time PCR Experiments (MIQE) guidelines. Guidelines published by Bustin et al 2009 were referred to in order to ensure accuracy and reliability of quantitative PCR data. (DOCX)
Article
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Venom is a critical evolutionary innovation enabling venomous snakes to become successful limbless predators; it is therefore vital that venomous snakes possess a highly efficient venom production and delivery system to maintain their predatory arsenal. Here, we exploit the unusual stability of messenger RNA in venom to conduct, for the first time,...
Data
Raw individual relative gene expression data generated by quantitative PCR. Raw qPCR data generated from relative expression analysis to show fold changes in expression of venom genes of interest, including snake venom metalloproteinase (SVMP), serine protease (SP), C-type lectin (CTL), Kunitz inhibitors (KTI), protein disulphide isomerase (PDI) an...
Article
Background: Snake venom metalloproteinases (SVMPs) are a pathologically-important, often major, toxin component of snake venoms, particularly in the venoms of viperid snakes. The SVMPs are members of the large multi-locus adamalysin gene family alongside ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) protein...
Article
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Serine proteases are major components of viper venom and target various stages of the blood coagulation system in victims and prey. A better understanding of the diversity of serine proteases and other enzymes present in snake venom will help to understand how the complexity of snake venom has evolved and will aid the development of novel therapeut...
Article
Gene duplication is a key mechanism for the adaptive evolution and neofunctionalization of gene families. Large multigene families often exhibit complex evolutionary histories as a result of frequent gene duplication acting in concordance with positive selection pressures. Alterations in the domain structure of genes, causing changes in the molecul...
Article
The proliferation of gene data from multiple loci of large multigene families has been greatly facilitated by considerable recent advances in sequence generation. The evolution of such gene families, which often undergo complex histories and different rates of change, combined with increases in sequence data, pose complex problems for traditional p...
Article
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Background: Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address...
Article
Antivenom is the most effective treatment of snake envenoming and is manufactured from the IgG of venom-immunised horses and sheep. Camelids have a unique IgG structure which may account for the report that camel IgG is less immunogenic and less likely to activate complement than equine or ovine IgG. Camelid IgG therefore offers potential safety ad...
Article
Camelid IgG has been reported to be less immunogenic, less able to activate the complement cascade and more thermostable than IgG from other mammals, and has the ability to bind antigens that are unreactive with other mammalian IgGs. We are investigating whether these attributes of camelid IgG translate into antivenom with immunological and venom-n...
Data
Comparison of computer generated tryptic digested peptides derived from the rhiminopeptidase A amino acid sequence with the MS/MS data from the purified protein. The figure shows the rhiminopeptidase A sequence with peptides matching the MS/MS data shown in bold red. The matched peptides cover 45% of the amino acid sequence, strongly suggesting tha...
Article
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Background: Snake bite is a major neglected public health issue within poor communities living in the rural areas of several countries throughout the world. An estimated 2.5 million people are bitten by snakes each year and the cost and lack of efficacy of current anti-venom therapy, together with the lack of detailed knowledge about toxic compone...
Article
Snake envenoming is a significant cause of mortality and morbidity in sub-Saharan Africa. The only effective treatment, antivenom, has been in short supply since the 1990s. Whilst the humanitarian response by some antivenom producers has significantly improved the situation, strategies to ensure the long term stability of antivenom supply are still...
Article
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Most epidemiological and clinical reports on snake envenoming focus on a single country and describe rural communities as being at greatest risk. Reports linking snakebite vulnerability to socioeconomic status are usually limited to anecdotal statements. The few reports with a global perspective have identified the tropical regions of Asia and Afri...
Article
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Bitis arietans is considered one of the most medically significant snakes in Africa, primarily due to a combination of its extensive geographical distribution, common occurrence and highly potent haemorrhagic and cytotoxic venom. Our investigation has revealed a remarkable degree of intra-species variation between pooled venom samples from differen...
Article
We report the 2DE-based proteomic characterization of the venom of the medically important African puff adder, Bitis arietans, after prefractionation by incubation with a solid-phase combinatorial hexapeptide ligand library (CPLL) at three different pH values. This approach yielded partially overlapping yet clearly distinct sets of proteins. The B....
Data
Summary statistics following clustering and assembling of ESTs for E. coloratus, E. p. leakeyi and E. c. sochureki.
Data