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[
Trends Genet,
2015]
Model organisms are of great importance to our understanding of basic biology and to making advances in biomedical research. However, the influence of laboratory cultivation on these organisms is underappreciated, and especially how that environment can affect research outcomes. Recent experiments led to insights into how the widely used laboratory reference strain of the nematode Caenorhabditis elegans compares with natural strains. Here we describe potential selective pressures that led to the fixation of laboratory-derived alleles for the genes
npr-1,
glb-5, and
nath-10. These alleles influence a large number of traits, resulting in behaviors that affect experimental interpretations. Furthermore, strong phenotypic effects caused by these laboratory-derived alleles hinder the discovery of natural alleles. We highlight strategies to reduce the influence of laboratory-derived alleles and to harness the full power of C. elegans.
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[
Biochem J,
2017]
Protein kinases form one of the largest protein families and are found in all species, from viruses to humans. They catalyze the reversible phosphorylation of proteins, often modifying their activity and localization. They are implicated in virtually all cellular processes and are one of the most intensively studied protein families. In recent years, they have become key therapeutic targets in drug development as natural mutations affecting kinase genes are the cause of many diseases. The vast amount of data contained in the primary literature and across a variety of biological data collections highlights the need for a repository where this information is stored in a concise and easily accessible manner. The UniProt Knowledgebase meets this need by providing the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information. Here, we describe the expert curation process for kinases, focusing on the Caenorhabditis elegans kinome. The C. elegans kinome is composed of 438 kinases and almost half of them have been functionally characterized, highlighting that C. elegans is a valuable and versatile model organism to understand the role of kinases in biological processes.
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[
Aging (Milano),
1993]
A central theme underlies this review: "Genetics offers an important tool for identifying key molecular events that are involved in specifying biological functions." This approach has been used repeatedly to understand such diverse biological phenomena as oncogenesis, development, and the cell cycle, but has only recently been applied to the analysis of organismic aging and senescence. The power of the genetic approach lies in the ability to integrate phenomena that are displayed at multiple observational levels (i.e., from the molecular to the whole organism), and the power to reveal causal factors that are not dependent upon the prejudice of the investigator. I discuss several areas where genetics has been fruitfully applied to the study of the aging processes: human genes identified by "segmental progeroid" mutations; neurological diseases of the elderly; the limited proliferative life span of human somatic cells in tissue culture; studies on the life span of the mouse; and genetic analysis of life span in shorter-lived metazoans (Drosophila melanogaster and Caenorhabditis elegans), and the yeast Saccaromyces cerevisiae.
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[
Geroscience,
2023]
A growing number of pharmaceutical and small molecule interventions are reported to extend the lifespan of laboratory animals including Caenorhabditis, Drosophila, and mouse. However, the degree to which these pro-longevity interventions are conserved across species is unclear. Here, we took two approaches to ask the question: to what extent do longevity intervention studies in Caenorhabditis and Drosophila recapitulate effects on mouse lifespan? The first approach analyzes all published reports on longevity in the literature collated by the DrugAge database, and the second approach focused on results designed for reproducibility as reported from the NIA-supported Interventions Testing Program (ITP) and the Caenorhabditis Interventions Testing Program (CITP). Using published data sources, we identify only modest sensitivity and specificity of Drosophila interventional studies for identifying pro-longevity compounds in mouse lifespan studies. Surprisingly, reported studies in C. elegans show little predictive value for identifying drugs that extend lifespan in mice. The results therefore suggest caution should be used when making assumptions about the translatability of lifespan-extending compounds across species, including human intervention.
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[
Toxics,
2020]
Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals that were widely used in manufacturing and are now present in the environment throughout the world. It is known that various PFAS are quantifiable in human in blood, but potential adverse health outcomes remain unclear. Sentinel and non-traditional model species are useful to study potential toxicity of PFAS in order to understand the relationship between environmental and human health. Here, we present a critical review of studies on the neurotoxicity of PFAS in sentinel and non-traditional laboratory model systems, including <i>Caenorhabditis elegans</i> (nematode), <i>Dugesia japonica</i> (planarian), <i>Rana pipiens</i> (frogs), <i>Danio rerio</i> and <i>Oryzias melastigma</i> (fish), and <i>Ursus maritimus</i> (polar bears). PFAS have been implicated in developmental neurotoxicity in non-traditional and traditional model systems as well as sentinel species, including effects on neurotransmitter levels, especially acetylcholine and its metabolism. However, further research on the mechanisms of toxicity needs to be conducted to determine if these chemicals are affecting organisms in a similar manner. Overall, findings tend to be similar among the various species, but bioaccumulation may vary, which needs to be taken into account in future studies by quantifying target organ concentrations of PFAS to better compare different species. Furthermore, data on the majority of PFAS is lacking in neurotoxicity testing, and additional studies are needed to corroborate findings thus far.
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[
Eur J Med Chem,
2017]
PAK family kinases are RAC/CDC42-activated kinases that were first found in a soil amoeba 4 decades ago, and 2 decades later, were discovered in mammals as well. Since then at least 6 members of this family have been identified in mammals. One of them called PAK1 has been best studied so far, mainly because it is essential not only for malignant cell growth and metastasis, but also for many other diseases/disorders such as diabetes (type 2), AD (Alzheimer's disease), hypertension, and a variety of inflammatory or infectious diseases, which definitely shorten our lifespan. Moreover, PAK1-deficient mutant of C.elegans lives longer than the wild-type by 60%, clearly indicating that PAK1 is not only an oncogenic but also ageing kinase. Thus, in theory, both anti-oncogenic and longevity-promoting activities are among the "intrinsic" properties or criteria of "clinically useful" PAK1-blockers. There are a variety of PAK1-blocking natural products such as propolis and curcumin which indeed extend the healthy lifespan of small animals such as C.elegans by inducing the autophagy. Recently, we managed to synthesize a series of potent water-soluble and highly cell-permeable triazolyl esters of COOH-bearing PAK1-blockers such as Ketorolac, ARC (artepillin C) and CA (caffeic acid) via "Click Chemistry" that boosts their anti-cancer activity over 500-fold, mainly by increasing their cell-permeability, and one of them called 15K indeed extends the lifespan of C.elegans. In this mini-review we shall discuss both synthetic and natural PAK1-blockers, some of which would be potentially useful for cancer therapy with least side effect (rather promoting the longevity as well).
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[
Studies of History & Philosophy of Science,
1998]
In 1963, just a year after the researchers of the Medical Research Council (MRC) Unit of Molecular Biology in Cambridge, joined by some other research groups, has moved from various scattered and makeshift buildings in the courtyard of the Physics Department to a lavishly funded four-storey laboratory, B. Lush, the Principal Medical Officer of the MRC, came to inquire about their plans for future expansion. He indicated that the MRC wished to build the laboratory up to what the principal researchers considered its 'final size' until their retirement, which meant planning ahead for at least 15 years. This surprising move was doubtless prompted by the recent award of the Nobel Prize to three members of the laboratory, Max Perutz, John Kendrew and Francis Crick, for their work on the molecular structure of proteins and nucleic acids. The triple award had propelled the new Laboratory of Molecular Biology into the limelight, and the MRC was interested in securing optimal research conditions for this prestigious group of researchers.
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[
Genome Biol,
2008]
ABSTRACT: A circuit of transcription factors has been discovered in Caenorhabditis elegans that could provide a link between laboratory-defined intracellular ''longevity pathways'', gene dysregulation and the process of normal aging.
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[
Biochem Soc Trans,
2019]
Reproducibility is critical for the standardization, interpretation, and progression of research. However, many factors increase variability and reduce reproducibility. In <i>Caenorhabditis elegans</i> research, there are many possible causes of variability that may explain why experimental outcomes sometimes differ between laboratories and between experiments. Factors contributing to experimental variability include the genetic background of both <i>C. elegans</i> and its bacterial diet, differences in media composition, intergenerational and transgenerational effects that may be carried over for generations, and the use of chemicals or reagents that may have unexpected consequences. This review summarizes sources of variability in <i>C. elegans</i> research and serves to identify laboratory practices that could influence reproducibility.
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[
Elife,
2015]
The roundworm Caenorhabditis elegans has risen to the status of a top model organism for biological research in the last fifty years. Among laboratory animals, this tiny nematode is one of the simplest and easiest organisms to handle. And its life outside the laboratory is beginning to be unveiled. Like other model organisms, C. elegans has a boom-and-bust lifestyle. It feasts on ephemeral bacterial blooms in decomposing fruits and stems. After resource depletion, its young larvae enter a migratory diapause stage, called the dauer. Organisms known to be associated with C. elegans include migration vectors (such as snails, slugs and isopods) and pathogens (such as microsporidia, fungi, bacteria and viruses). By deepening our understanding of the natural history of C. elegans, we establish a broader context and improved tools for studying its biology.