A5064546730- Parasites and Host Interactions
- Helminth infection and control
- Glutathione Transferases and Polymorphisms
- Research on Leishmaniasis Studies
- Parasite Biology and Host Interactions
- Trypanosoma species research and implications
- Coccidia and coccidiosis research
- Genetics, Aging, and Longevity in Model Organisms
- Trace Elements in Health
- RNA Research and Splicing
- Insect symbiosis and bacterial influences
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Selenium in Biological Systems
- Extracellular vesicles in disease
- Drug-Induced Hepatotoxicity and Protection
- Heat shock proteins research
- Parasitic Infections and Diagnostics
- CRISPR and Genetic Engineering
Liverpool School of Tropical Medicine
2008-2023
Institute of Biological, Environmental and Rural Sciences
2008-2020
Aberystwyth University
2005-2020
University of Liverpool
2008-2010
Queen's University Belfast
2010
University of Wales
2005
Novel methods to identify anthelmintic drug and vaccine targets are urgently needed, especially for those parasite species currently being controlled by singular, often limited strategies. A clearer understanding of the transcriptional components underpinning helminth development will enable identification exploitable molecules essential successful parasite/host interactions. Towards this end, we present a combinatorial, bioinformatics-led approach, employing both statistical network...
Hookworm glutathione S-transferases (GSTs) are critical for parasite blood feeding and survival represent potential targets vaccination. Three cDNAs, each encoding a full-length GST protein from the human hookworm Necator americanus (and designated Na-GST-1, Na-GST-2, Na-GST-3, respectively) were isolated cDNA based on their sequence similarity to Ac-GST-1, dog Ancylostoma caninum. The open reading frames of three N. GSTs contain 206 amino acids with 51% 69% identity between other Ac-GST-1....
Background Liver fluke infection of livestock causes economic losses over US$ 3 billion worldwide per annum. The disease is increasing in and a re-emerging human disease. There are currently no commercial vaccines, only one drug with significant efficacy against adult worms juveniles. A liver vaccine deemed essential as short-lived chemotherapy, which prone to resistance, an unsustainable option both developed developing countries. Protein superfamilies have provided number leading...
We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from adult hookworm Ancylostoma caninum, its possible role in parasite blood feeding as vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) exhibited up to 65% acid identity with other nematode GSTs. mRNA encoding was detected adults, eggs, larval stages, but protein only somatic extracts excretory/secretory products. Using antiserum recombinant protein,...
Control of Fasciola hepatica infections livestock in the absence vaccines depends largely on chemical triclabendazole (TCBZ) because it is effective against immature and adult parasites. Overdependence a single drug improper application considered significant factor increasing global reports fluke resistant to TCBZ. The mode(s) action biological target(s) TCBZ are not confirmed, delaying detection monitoring early resistance. In this study, further understand liver response TCBZ, soluble...
In contrast to their mammalian hosts, parasitic nematodes are heme auxotrophs and require pathways for the uptake transport of exogenous incorporation into hemoproteins. Phase II detoxification Nu-class glutathione transferase (GST) proteins have a proposed role as heme-binding ligandins in nematodes. The genome-verified free-living nematode Caenorhabditis elegans also cannot synthesize is an ideal functional genomics model delineate individual GSTs trafficking detoxification. this study, C....
Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health economic losses estimated at several billion US$. Fasciola hepatica the major species in temperate regions, while F. gigantica dominates tropics. In absence commercially available vaccines to control fasciolosis, increasing reports resistance current chemotherapeutic strategies spread fasciolosis into new areas, functional genomics approaches are being used identify potential drug...
Lack of genomic sequence data and the relatively high cost tandem mass spectrometry have hampered proteomic investigations into helminths, such as resolving mechanism underpinning globally reported anthelmintic resistance. Whilst detailed mechanisms resistance remain unknown for majority drug-parasite interactions, gene mutations changes in protein expression are proposed key aspects Comparative analysis drug-resistant -susceptible nematodes may reveal profiles reflecting drug-related...
The insulin/insulin-like growth factor-1 (IGF-1) signaling system is a public regulator of aging in the model animals Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. For first time, proteomic analyses environmentally resistant 'nonaging' C. elegans dauer stage long-lived daf-2 mutants has provided unique insight into protein changes which mediate survival against endogenously produced toxins. These support diversion energy consumption away from anabolic processes toward...
Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the expression of invariant antigens. Proteomic analyses saliva from T . -infected flies identified, in addition to VSG and Brucei Alanine-Rich Protein (BARP) peptides, family glycosylphosphatidylinositol (GPI)-anchored proteins herein named as Metacyclic Invariant Surface Proteins (MISP) because...
Schistosoma mansoni venom allergen-like proteins (SmVALs) are part of a diverse protein superfamily partitioned into two groups (group 1 and group 2). Phylogenetic analyses SmVALs revealed that members could be segregated subclades (A-D); these share similar gene expression patterns across the parasite lifecycle immunological cross-reactivity. Furthermore, whole-mount in situ hybridization demonstrated phylogenetically, transcriptionally immunologically-related SmVAL4, 10, 18 19 (subclade C)...
Loss-of-function phenotypic analysis via interference RNA (RNAi) technology is a revolutionary approach to assigning gene function. While transcript-based methodologies commonly validate RNAi suppression investigations, protein-based validation less developed. This report illustrates the potential for two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-DE) and quantify protein levels following RNAi. case study involves three glutathione transferase (GST) genes...
Abstract Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside the tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, nothing is known about expression of invariant antigens by stage. Proteomic analysis saliva from T. -infected flies revealed novel family hypothetical GPI-anchored proteins herein named Metacyclic Invariant Surface Proteins (MISP). MISP are encoded five homolog genes and share ~80% protein identity. The...
The Schistosoma mansoni venom allergen-like protein (SmVAL) superfamily is a collection of at least 29 molecules that have been classified into two distinctive groups (Group 1 and Group 2 SmVALs). fundamental basis for SmVAL segregation relates to signal peptide conserved cysteine retention (present in all SmVALs, but absent These structural differences led the hypothesis most found as components schistosome excretory/secretory (E/S) products, predominantly interact with their environment...
African sleeping sickness is caused by Trypanosoma brucei , a parasite transmitted the bite of tsetse fly. Trypanosome infection induces severe transcriptional downregulation genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission possible role glycans in insect bloodfeeding, we characterized N -glycome saliva glycoproteins. Tsetse -glycans were enzymatically released, tagged with either...
Abstract Filarial nematodes possess glutathione transferases (GSTs), ubiquitous enzymes with the potential to detoxify xenobiotic and endogenous substrates, modulate host immune system, which may aid worm infection establishment, maintenance survival in host. Here we have identified characterized a σ class glycosylated GST (OoGST1), from cattle-infective filarial nematode Onchocerca ochengi, is homologous (99% amino acid identity) an immunodominant vaccine candidate human parasite, O....
Abstract African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted the bite of tsetse fly. Trypanosome infection induces severe transcriptional downregulation genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission possible role glycans in insect bloodfeeding, we characterized N -glycome saliva glycoproteins. Tsetse -glycans were enzymatically released, tagged with either...