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Introduction
I am a molecular and computational biologist focused on understanding the evolutionary biology of parasitic worms that infect humans and animals. I lead a multidisciplinary research group where we use population-wide to single-cell resolution genomic approaches to understand the genetic mechanisms and phenotypic traits underpinning parasite adaptation and persistence.
Current institution
Additional affiliations
September 2020 - present
September 2015 - present
January 2012 - present
Education
February 2006 - October 2010
January 2005 - November 2005
February 2001 - November 2004
Publications
Publications (195)
New approaches are urgently needed to enrich rare or low-abundant DNA in complex samples. Soil-transmitted helminths (STHs) inhabit heterogeneous environments, including the gastrointestinal tract of their host as adults and are excreted as eggs and larvae in faeces, complicating our understanding of their biology and the use of genetic tools for s...
The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Asse...
Whipworms (Trichuris spp) are ubiquitous parasites of humans and domestic and wild mammals that cause chronic disease, considerably impacting human and animal health. Egg hatching is a critical phase in the whipworm life cycle that marks the initiation of infection, with newly hatched larvae rapidly migrating to and invading host intestinal epithel...
We present a genome assembly from a specimen of Opisthorchis viverrini (liver fluke; Platyhelminthes; Trematoda; Opisthorchiida; Opisthorchiidae). The genome sequence has a total length of 627.20 megabases. Most of the assembly (97.89%) is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.04 k...
Heartworms (Dirofilaria immitis) are parasitic nematodes that cause significant cardiopulmonary-associated morbidity and mortality in canids worldwide. The global dissemination of heartworms is believed to have occurred alongside the dispersal of domesticated dogs. To test this theory, we performed the largest population genetics study of heartworm...
Reconciling organism-scale biology at cellular-scale resolution has been a monumental challenge. Recently, Gramberg et al. uncovered the spatial organisation of gene expression in the common liver fluke, Fasciola hepatica. These data provide new insights and opportunities for understanding the fundamental developmental and functional biology of par...
Single-cell/nuclei transcriptomics has revolutionised our understanding of cell, tissue, and organismal biology during health and disease of humans and model organisms. However, for non-model species, reassessment and refinement of conventional methods to address novel technical and biological challenges are needed. Here, we evaluate three establis...
Concerns about the emergence of benzimidazole resistance in soil-transmitted helminths (STH) infections, particularly against Trichuris trichiura, have arisen. Previous studies of veterinary nematodes have linked benzimidazole resistance to single-nucleotide polymorphisms (SNPs) at three specific codons in the beta-tubulin gene, but similar associa...
Soil-transmitted helminths (STHs) are intestinal pathogens affecting over a billion people worldwide. STH control relies on microsopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance, however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence set...
Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni sample...
Schistosoma mansoni is a parasitic flatworm that causes the major neglected tropical disease schistosomiasis. The miracidium is the first larval stage of the life cycle. It swims and infects a freshwater snail, transforms into a mother sporocyst, where its stem cells generate daughter sporocysts that give rise to human-infective cercariae larvae. T...
Whipworms ( Trichuris spp) are ubiquitous parasites of humans and domestic and wild mammals that cause chronic disease, considerably impacting human and animal health. Egg hatching is a critical phase in the whipworm life cycle that marks the initiation of infection, with newly hatched larvae rapidly migrating to and invading host intestinal epithe...
Schistosomes are parasitic flatworms that cause the water-borne disease schistosomiasis, affecting millions of people worldwide. The miracidium larva of schistosomes represents the first post-embryonic stage of development and is critical to transmission. After hatching, a miracidium infects a freshwater snail and transforms into a mother sporocyst...
The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goat farming in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate MTci2...
Schistosomes are parasitic flatworms that cause the water-borne disease schistosomiasis, affecting millions of people worldwide. The miracidium larva of schistosomes represents the first post-embryonic stage of development and is critical to transmission. After hatching, a miracidium infects a freshwater snail and transforms into a mother sporocyst...
Schistosomes are parasitic flatworms that cause the water-borne disease schistosomiasis, affecting millions of people worldwide. The miracidium larva of schistosomes represents the first post-embryonic stage of development and is critical to transmission. After hatching, a miracidium infects a freshwater snail and transforms into a mother sporocyst...
Background
The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some par...
Recently, a S168T variant in the acetylcholine receptor subunit ACR-8 was associated with levamisole resistance in the parasitic helminth Haemonchus contortus. Here, we used the Xenopus laevis oocyte expression system and two-electrode voltage-clamp electrophysiology to measure the functional impact of this S168T variant on the H. contortus levamis...
Haemonchus contortus is a parasitic haematophagous nematode that primarily affects small ruminants and causes significant economic loss to the global livestock industry. Treatment of haemonchosis typically relies on broad-spectrum anthelmintics, resistance to which is an important cause of treatment failure. Resistance to levamisole remains less wi...
The flatworm Schistosoma mansoni is an important but neglected pathogen that causes the disease schistosomiasis in millions of people worldwide. The parasite has a complex life cycle, undergoing sexual reproduction in a mammalian host and asexual replication in a snail host. Understanding the molecular mechanisms that the parasite uses to transitio...
Background
The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some par...
The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This stu...
Our knowledge of the diet of wild octopus paralarvae, Octopus vulgaris, is restricted to the first 2 weeks of its planktonic phase when they are selective hunters found near the coastline. These small paralarvae, bearing only three suckers per arm, are transported by oceanic currents from the coast towards offshore waters, where they complete the p...
The flatworm Schistosoma mansoni is an important but neglected pathogen that causes the disease schistosomiasis in millions of people worldwide. The parasite has a complex life cycle, undergoing sexual reproduction in a mammalian host and asexual replication in a snail host. Understanding the molecular mechanisms the parasite uses to transition bet...
The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This stu...
Schistosomes are parasitic flatworms whose infections affect millions of people worldwide. The parasite has a complex life cycle that is poorly understood at a cellular level. We have developed a cellular transcriptome atlas of the miracidium larva of Schistosoma mansoni, the first post-embryonic stage of development. The miracidium infects a snail...
The identification of gastrointestinal helminth infections of humans and livestock almost exclusively relies on the detection of eggs or larvae in faeces, followed by manual counting and morphological characterisation to differentiate species using microscopy-based techniques. However, molecular approaches based on the detection and quantification...
Our knowledge of the diet of wild Octopus vulgaris is restricted to the first two weeks of its planktonic phase when they are selective hunters found in the coastal area. These small paralarvae, bearing only three suckers per arm, are transported by oceanic currents from the coast towards offshore waters where they complete the planktonic phase in...
Like other pathogens, parasitic helminths can rapidly evolve resistance to drug treatment. Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking its spread and improving the efficacy and sustainability of parasite control. Here, we use an in vivo genetic cross between drug-susceptible and multi-dr...
Understanding the composition of gastrointestinal nematode (GIN) communities may help to mitigate or exploit parasite adaptations within their host. We have used nemabiome deep amplicon sequencing of internal transcribed spacer-2 (ITS-2) ribosomal DNA to describe the temporal and host species composition of GIN communities following sampling of six...
Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic d...
Haemonchus contortus is a haematophagous parasitic nematode that infects small ruminants and causes significant animal health concerns and economic losses within the livestock industry on a global scale. Treatment primarily depends on broad-spectrum anthelmintics, however, resistance is established or rapidly emerging against all major drug classes...
The neglected tropical disease trichuriasis is caused by the whipworm Trichuris trichiura,a soil-transmitted helminth that has infected humans for millennia. Today, T. trichiura infects as many as 500 million people, predominantly in communities with poor sanitary infrastructure enabling sustained faecal-oral transmission. Using whole-genome sequen...
Rapid advancement in high-throughput sequencing and analytical approaches has seen a steady increase in the generation of genomic resources for helminth parasites. Now, helminth genomes and their annotations are a cornerstone of numerous efforts to compare genetic and transcriptomic variation, from single cells to populations of globally distribute...
In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021–30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the effici...
The antiparasitic drug ivermectin plays an essential role in human and animal health globally. However, ivermectin resistance is widespread in veterinary helminths and there are growing concerns of sub-optimal responses to treatment in related helminths of humans. Despite decades of research, the genetic mechanisms underlying ivermectin resistance...
Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficac...
Haemonchus contortus is a haematophagous parasitic nematode that infects small ruminants and causes significant animal health concerns and economic losses within the livestock industry on a global scale. Treatment primarily depends on broad-spectrum anthelmintics, however, resistance is established or rapidly emerging against all major drug classes...
Gastrointestinal (GI) helminth infections cause significant morbidity in both humans and animals worldwide. Specific and sensitive diagnosis is central to the surveillance of such infections and to determine the effectiveness of treatment strategies used to control them. In this article, we: (i) assess the strengths and limitations of existing meth...
The anthelmintic praziquantel (PZQ) is an essential tool in controlling schistosomiasis, so reports of reduced PZQ efficacy are of great public health concern. Le Clec'h et al. recently identified a gene responsible for PZQ resistance in experimentally selected resistant Schistosoma mansoni. The importance of this locus in natural infections remain...
Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic d...
We present a genome assembly and annotation of an individual female Cercopithifilaria johnstoni , a parasitic filarial nematode that is transmitted by hard ticks (Ixodidae) to infect a broad range of native Australian murid and marsupial hosts. The genome sequence is 76.9 Mbp in length, and although in draft form (N50 = 99 kbp, N50[n] = 232), is la...
Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed...
Haemonchus contortus is a pathogenic gastrointestinal nematode of small ruminants and, in part due to its capacity to develop resistance to drugs, contributes to significant losses in the animal production sector worldwide. Despite decades of research, comparatively little is known about the specific mechanism(s) driving resistance to drugs such as...
Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to improving the efficacy and sustainability of parasite control. Here, we use a genetic cross in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies novel alleles for...
The antiparasitic drug ivermectin plays an essential role in human and animal health globally. However, ivermectin resistance is widespread in veterinary helminths and there are growing concerns of sub-optimal responses to treatment in related helminths of humans. Despite decades of research, the genetic mechanisms underlying ivermectin resistance...
The neglected tropical disease trichuriasis is caused by the whipworm Trichuris trichiura, a soil-transmitted helminth that has infected humans for millennia. Today, T. trichiura infects as many as 500 million people, predominantly in communities with poor sanitary
infrastructure enabling sustained faecal-oral transmission. Using whole-genome seque...
We present a genome assembly and annotation of an individual female Cercopithifilaria johnstoni , a parasitic filarial nematode that is transmitted by hard ticks (Ixodidae) to infect a broad range of native Australian murid and marsupial hosts. The genome sequence is 76.9 Mbp in length, and although in draft form (N50 = 99 kbp, N50[n] = 232), is la...
Background
Schistosoma mansoni is a flatworm that causes a neglected tropical disease affecting millions worldwide. Most flatworms are hermaphrodites but schistosomes have genotypically determined male (ZZ) and female (ZW) sexes. Sex is essential for pathology and transmission, however, the molecular determinants of sex remain unknown and is limite...
Despite the prevalence of sclerophyllous vegetation in Australia, there are few phylogeographic studies with continent-wide sampling addressing questions about the expansion of this vegetation post-aridification, and what physical barriers are associated with breaks in distribution or patterns of genetic structure. We used amplicon sequencing of pl...
Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Humans become infected by free-swimming, water-borne larvae, which penetrate the skin. The earliest intra-mammalian stage, called the schistosomulum, undergoes a series of developmental transitions. These changes are critical...
Anthelmintic resistance is a significant threat to livestock production systems worldwide and is emerging as an important issue in companion animal parasite management. It is also an emerging concern for the control of human soil-transmitted helminths and filaria. An important aspect of managing anthelmintic resistance is the ability to utilise dia...
Background
Guinea worm–Dracunculus medinensis–was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 54 human cases reported glob...
Background: Chromosome-level assemblies are indispensable for accurate gene prediction, synteny assessment, and understanding higher-order genome architecture. Reference and draft genomes of key helminth species have been published, but little is yet known about the biology of their chromosomes. Here, we present the complete genome of the tapeworm...
Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X...
Background
Chromosome-level assemblies are indispensable for accurate gene prediction, synteny assessment, and understanding higher-order genome architecture. Reference and draft genomes of key helminth species have been published, but little is yet known about the biology of their chromosomes. Here, we present the complete genome of the tapeworm H...
Background: Chromosome-level assemblies are indispensable for accurate gene prediction, synteny assessment and understanding higher-order genome architecture. Reference and draft genomes of key helminth species have been published but little is yet known about the biology of their chromosomes. Here we present the complete genome of the tapeworm Hym...
Background: Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants, and has become the key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Two draft genome assemblies for H. contort...
Background: Guinea worm - Dracunculus medinensis - was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 30 human cases reported...
Plant defensins are a large family of proteins, most of which have antifungal activity against a broad spectrum of fungi. However, little is known about how they exert their activity. The mechanism of action of only a few members of the family have been investigated and, in most cases, there are still a number of unknowns. To gain a better understa...
Haemonchus contortus is a haematophagous parasitic nematode of veterinary interest. We have performed a survey of its genome-wide diversity using single-worm whole genome sequencing of 223 individuals sampled from 19 isolates spanning five continents. We find an African origin for the species, together with evidence for parasites spreading during t...
Whole-genome sequencing is being rapidly applied to the study of helminth genomes, including de novo genome assembly, population genetics, and diagnostic applications. Although late-stage juvenile and adult parasites typically produce sufficient DNA for molecular analyses, these parasitic stages are almost always inaccessible in the live host; imma...
Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Humans become infected by free-swimming, water-borne larvae, which penetrate the skin. The earliest intra-mammalian stage, called the schistosomulum, undergoes a series of developmental transitions. These changes are critical...
Differential expression analysis between parasitic nematode strains is commonly used to implicate candidate genes in anthelmintic resistance or other biological functions. We have tested the hypothesis that the high genetic diversity of an organism such as Haemonchus contortus could complicate such analyses. First, we investigated the extent to whi...
In 2012, the reduction in Onchocerca volvulus infection prevalence through long-term mass ivermectin distribution in African meso- and hyperendemic areas motivated expanding control of onchocerciasis (river blindness) as a public health problem to elimination of parasite transmission. Given the large contiguous hypo-, meso- and hyperendemic areas w...
Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in ‘refugia’, unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, ev...
Whole genome sequencing is being rapidly applied to the study of helminth genomes, including de novo genome assembly, population genetics, and diagnostic applications. Although late-stage juvenile and adult parasites typically produce sufficient DNA for molecular analyses, these parasitic stages are almost always inaccessible in the live host; imma...
Background
Infections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths...
Many marine species once considered to be cosmopolitan are now recognised as cryptic species complexes. Mitochondrial markers are ubiquitously used to address phylogeographic questions, and have been used to identify some cryptic species complexes; however, their efficacy in inference of evolutionary processes in the nuclear genome has not been tho...
The rapid evolution of anthelmintic resistance in a number of parasites of livestock and domesticated animals has occurred in response to widespread use of anthelmintics for parasite control, and threatens the success of parasite control of species that infect humans. The genetic basis of resistance to most anthelmintics remains poorly resolved. Ge...
Genetic differentiation is characteristically weak in marine species making assessments of population connectivity and structure difficult. However, the advent of genomic methods has increased genetic resolution, enabling studies to detect weak, but significant population differentiation within marine species. With an increasing number of studies e...
Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative
study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds...
Background: Wolbachia are important endosymbionts of filarial parasites. The Wolbachia of Onchocerca volvulus, the filarial pathogen responsible for the human disease onchocerciasis, is implicated in the immunopathology of the disease and may be associated with disease severity dependent on the density of Wolbachia. However, little is known in rega...
The gastrointestinal parasite Haemonchus contortus is the most pathogenic nematode of veterinary interest and a model for many aspects of parasitic nematode biology. Using single-worm whole genome sequencing, we have performed the most exhaustive survey of genome-wide diversity undertaken for any parasitic nematode, considering 19 populations spann...
Genetic crosses were undertaken between the anthelmintic sensitive genome strain of H. contortus-MHco3 (ISE) and a multi-drug resistant strain-MHco18 (UGA) derived from southern USA. One hundred female (MHco3) and 100 male (MHco18) and vice versa immature day 14 post infection larvae were surgically transferred to the abomasa of recipient sheep. Th...
A 'sibling' species of the model organism Caenorhabditis elegans has long been sought for use in comparative analyses that would enable deep evolutionary interpretations of biological phenomena. Here, we describe the first sibling species of C. elegans, C. inopinata n. sp., isolated from fig syconia in Okinawa, Japan. We investigate the morphology,...
Helminth infections cause an enormous disease burden in humans, livestock and companion animals. Helminth control is heavily dependent on the regular administration of anthelmintic drugs. Resistance to these drugs is widespread in many livestock systems, and there is concern that mass drug administration programs to control human helminths may be s...
The parasitic nematode Haemonchus contortus is an economically and clinically important pathogen of small ruminants, and a model system for understanding the mechanisms and evolution of traits such as anthelmintic resistance. Anthelmintic resistance is widespread and is a major threat to the sustainability of livestock agriculture globally; however...
The parasitic nematode Haemonchus contortus is an economically and clinically important pathogen of small ruminants, and a model system for understanding the mechanisms and evolution of traits such as anthelmintic resistance. Anthelmintic resistance is widespread and is a major threat to the sustainability of livestock agriculture globally; however...
Background
Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana―exposed to...
Background
Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to...
