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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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Trends Genet,
2021]
Although many studies have examined quantitative trait variation across many species, only a small number of genes and thereby molecular mechanisms have been discovered. Without these data, we can only speculate about evolutionary processes that underlie trait variation. Here, we review how quantitative and molecular genetics in the nematode Caenorhabditis elegans led to the discovery and validation of 37 quantitative trait genes over the past 15 years. Using these data, we can start to make inferences about evolution from these quantitative trait genes, including the roles that coding versus noncoding variation, gene family expansion, common versus rare variants, pleiotropy, and epistasis play in trait variation across this species.
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Int J Mol Sci,
2019]
Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in <i>Caenorhabditis elegans</i> and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this review, we highlight the current research on the structural diversity, biosynthesis, and pleiotropic neuronal functions of ascr pheromones and their implications in animal physiology. Experimental evidence suggests that ascr biosynthesis starts with conjugation of ascarylose to very long-chain fatty acids that are then processed via peroxisomal -oxidation to yield diverse ascr pheromones. We also discuss the concentration and stage-dependent pleiotropic neuronal functions of ascr pheromones. These functions include dauer induction, lifespan extension, repulsion, aggregation, mating, foraging and detoxification, among others. These roles are carried out in coordination with three G protein-coupled receptors that function as putative pheromone receptors: SRBC-64/66, SRG-36/37, and DAF-37/38. Pheromone sensing is transmitted in sensory neurons via DAF-16-regulated glutamatergic neurotransmitters. Neuronal peroxisomal fatty acid -oxidation has important cell-autonomous functions in the regulation of neuroendocrine signaling, including neuroprotection. In the future, translation of our knowledge of nematode ascr pheromones to higher animals might be beneficial, as ascr#1 has some anti-inflammatory effects in mice. To this end, we propose the establishment of <b> <i>pheromics</i> </b> (<i>pher</i>omone <i>o</i><i>mics</i>) as a new subset of integrated disciplinary research area within chemical ecology for system-wide investigation of animal pheromones.
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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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WormBook,
2010]
The nervous system represents the most complex tissue of C. elegans both in terms of numbers (302 neurons and 56 glial cells = 37% of the somatic cells in a hermaphrodite) and diversity (118 morphologically distinct neuron classes). The lineage and morphology of each neuron type has been described in detail and neuronal fate markers exists for virtually all neurons in the form of fluorescent reporter genes. The ability to "phenotype" neurons at high resolution combined with the amenability of C. elegans to genetic mutant analysis make the C. elegans nervous system a prime model system to elucidate the nature of the gene regulatory programs that build a nervous system-a central question of developmental neurobiology. Discussing a number of regulatory genes involved in neuronal lineage determination and neuronal differentiation, I will try to carve out in this review a few general principles of neuronal development in C. elegans. These principles may be conserved across phylogeny.