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Int J Parasitol,
2001]
The future direction of post-genomic nematode parasitology should focus on the function of the genes that are defined by large-scale expressed sequence tag sequencing and on broader questions about the genetic basis of parasitism. Functional characterisation will require the application of high throughput technologies that have been developed in other fields, including genome mapping strategies and DNA microarray analysis. These will be greatly aided by the development and application of appropriate model organisms. It is: crucial that the field make the transition from a narrow focus on one or a few genes at a time to a focus on whole genomes in order to fully realise the potential of the expressed sequence tag and other genomic projects currently under way.
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Methods,
2016]
The localization of a protein is intrinsically linked to its role in the structural and functional organization of the cell. Advances in transgenic technology have streamlined the use of protein localization as a function discovery tool. Here we review the use of large genomic DNA constructs such as bacterial artificial chromosomes as a transgenic platform for systematic tag-based protein function exploration.
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Trends in Parasitology,
2005]
Expressed sequence tag projects have currently produced over 400 000 partial gene sequences from more than 30 nematode species and the full genomic sequences of selected nematodes are being determined. In addition, functional analyses in the model nematode Caenorhabditis elegans have addressed the role of almost all genes predicted by the genome sequence. This recent explosion in the amount of available nematode DNA sequences, coupled with new gene function data, provides an unprecedented opportunity to identify pre-validated drug targets through efficient mining of nematode genomic databases. This article describes the various information sources available and strategies that can expedite this process.
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Parasitology,
1999]
The initiation of genome projects on helminths of medical importance promises to yield new drug targets and vaccine candidates in unprecedented numbers. In order to exploit this emerging data it is essential that the user community is aware of the scope and quality of data available, and that the genome projects provide analyses of the raw data to highlight potential genes of interest. Core bioinformatics support for the parasite genome projects has promoted these approaches. In the Brugia genome project, a combination of expressed sequence tag sequencing from multiple DNA libraries representing the complete filarial nematode lifecycle, and comparative analysis of the sequence dataset, particularly using the complete genome sequence of the model nematode C. elegans, has proved very effective in gene discovery.
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Med Microbiol Immunol,
2006]
Parasitic nematodes are widespread and important pathogens of humans and other animals. The parasitic nematodes Strongyloides have an unusual life cycle in which there is a facultative free-living generation in addition to the obligate parasitic generation. The genomes of many species of parasitic nematodes, including Strongyloides ratti and Strongyloides stercoralis, have been investigated, principally by expressed sequence tag (EST) analyses. These have discovered very many genes from these parasites but, in so doing, have also revealed how different these species are from each other and from other organisms. Understanding the role and function of these newly discovered genes is now the challenge, made more difficult by the parasitic lifestyle. The genomic information available for parasitic nematodes is allowing new approaches for the control of parasitic nematodes to be considered.
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Parasitol Today,
2000]
Gene discovery programs centred around expressed sequence tag (EST) and genome sequencing projects have predictably led to an exponential surge in the number of parasite gene sequences deposited in public databases. To take advantage of this wealth of sequence information, it is essential to develop rapid methods for elucidating the biological function or mode of action of individual genes. Here, Patricia Kuwabara and Alan Coulson discuss the virtues of a powerful epigenetic gene disruption technique, RNA-mediated interference (RNAi), which was originally developed for the nematode Caenorhabditis elegans. It is anticipated that this technique will not only provide insights into gene function, but also help investigators to mine the genome for candidate drug intervention or vaccine development targets, some of which may not be readily apparent on the basis of sequence information alone.
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Annu Rev Phytopathol,
2009]
Plant nematology is currently undergoing a revolution with the availability of the first genome sequences as well as comprehensive expressed sequence tag (EST) libraries from a range of nematode species. Several strategies are being used to exploit this wealth of information. Comparative genomics is being used to explore the acquisition of novel genes associated with parasitic lifestyles. Functional analyses of nematode genes are moving toward larger scale studies including global transcriptome profiling. RNA interference (RNAi) has been shown to reduce expression of a range of plant parasitic nematode genes and is a powerful tool for functional analysis of nematode genes. RNAi-mediated suppression of genes essential for nematode development, survival, or parasitism is revealing new targets for nematode control. Plant nematology in the genomics era is now facing the challenge to develop RNAi screens adequate for high-throughput functional analyses.
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Curr Top Membr,
2015]
The nematode worm Caenorhabditis elegans has all the major basement membrane proteins found in vertebrates, usually with a smaller gene family encoding each component. With its powerful forward genetics, optical clarity, simple tissue organization, and the capability to functionally tag most basement membrane components with fluorescent proteins, C. elegans has facilitated novel insights into the assembly and function of basement membranes. Although basement membranes are generally thought of as static structures, studies in C. elegans have revealed their active properties and essential functions in tissue formation and maintenance. Here, we review discoveries from C. elegans development that highlight dynamic aspects of basement membrane assembly, function, and regulation during organ growth, tissue polarity, cell migration, cell invasion, and tissue attachment. These studies have helped transform our view of basement membranes from static support structures to dynamic scaffoldings that play broad roles in regulating tissue organization and cellular behavior that are essential for development and have important implications in human diseases.
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Parasite Immunol,
2001]
Filarial nematodes are metazoan parasites with genome sizes of> 100 million base pairs, probably encoding 15 000-20 000 genes. Within this considerable gene complement, it seems likely that filariae have evolved a spectrum of immune evasion products which underpin their ability to live for many years within the human host. Moreover, no suitable vaccine currently exists for human filarial diseases, and few markers have yet been established for diagnostic use. In this review, we bring together biochemical and immunological data on prominent filarial proteins with the exciting new information provided by the Filarial Genome Project's expressed sequence tag (EST) database. In this discussion, we focus on those genes with the highest immunological profile, such as inhibitors of host enzymes, cytokine homologues and stage-specific surface proteins, as well as products associated with the mosquito-borne infective larva which offer the best opportunity for an anti-filarial vaccine. These gene products provide a fascinating glimpse of the molecular repertoire which helminth parasites have evolved to manipulate and evade the mammalian immune response.
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Front Mol Neurosci,
2020]
Neuromuscular development is a multistep process and involves interactions among various extracellular and transmembrane molecules that facilitate the precise targeting of motor axons to synaptogenic regions of the target muscle. Collagenous proteins with transmembrane domains have recently emerged as molecules that play essential roles in multiple aspects of neuromuscular formation. Membrane-associated collagens with interrupted triple helices (MACITs) are classified as an unconventional subtype of the collagen superfamily and have been implicated in cell adhesion in a variety of tissues, including the neuromuscular system. Collagen XXV, the latest member of the MACITs, plays an essential role in motor axon growth within the developing muscle. In humans, loss-of-function mutations of collagen XXV result in developmental ocular motor disorders. In contrast, collagen XIII contributes to the formation and maintenance of neuromuscular junctions (NMJs), and disruption of its function leads to the congenital myasthenic syndrome. Transmembrane collagens are conserved not only in mammals but also in organisms such as <i>C. elegans</i>, where a single MACIT, COL-99, has been documented to function in motor innervation. Furthermore, in <i>C. elegans</i>, a collagen-like transmembrane protein, UNC-122, is implicated in the structural and functional integrity of the NMJ. This review article summarizes recent advances in understanding the roles of transmembrane collagens and underlying molecular mechanisms in multiple aspects of neuromuscular development and disorders.