Greenwald IS et al. (1990) Cell "Cell fates in C. elegans: in medias ras."

Greenwald IS, Broach JR

[Cell, 1990]

ras proteins play a central role in controlling cell proliferation in a variety of organisms and also appear to mediate specific developmental processes in certain cells. Nonetheless, how ras protein activity is regulated and how ras protein activation yields its biological effect have not been clearly defined in any metazoan. Now, Han and Sternberg (1990a) have found that a ras protein is encoded by the C. elegans let-60 gene. Since powerful classical and molecular genetic methods are available for C. elegans, this finding offers great promise for identifying components of the ras pathway and defining the nature of their interactions in this organism. In addition, the extensive literature on the biochemistry and genetics of ras function in other organisms should greatly facilitate translating genetic analysis of let-60 (Beitel et al., 1990; Han and Sternberg, 1990b) into detailed molecular models of cell fate determination.

Link CD (2006) Exp Gerontol "C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer's disease."

Link CD

[Exp Gerontol, 2006]

Caenorhabditis elegans has been used to model aspects of a number of age-associated neurodegenerative diseases, including Alzheimer''s, Parkinson''s and Huntington''s diseases. These models have typically involved the transgenic expression of disease-associated human proteins. Here I describe my laboratory''s specific experience engineering C. elegans models of Alzheimer''s disease, and give a general consideration of the advantages and disadvantages of these C. elegans models. The type of insights that might be gained from using these (relatively) simple models are highlighted. In particular, I consider the potential these models have for uncovering common and unique fundamental toxic mechanisms underlying human neurodegenerative diseases.

Meier B et al. (2001) Curr Biol "Checkpoints: chromosome pairing takes an unexpected twist."

Ahmed S, Meier B

[Curr Biol, 2001]

When meiotic cells complete S phase, homologous chromosomes pair, synapse and undergo recombination. A checkpoint protein is somehow required for meiotic chromosome pairing in C. elegans, thus providing a direct link between S phase and the rest of the meiotic program.

Kong C et al. (2016) Toxins (Basel) "Targeting Staphylococcus aureus Toxins: A Potential form of Anti-Virulence Therapy."

Nathan S, Neoh HM, Kong C

[Toxins (Basel), 2016]

Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. The range of diseases reflects the diversity of virulence factors produced by this pathogen. To establish an infection in the host, S. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria's ability to spread through tissues. Expression and secretion of this array of toxins and enzymes are tightly controlled by a number of regulatory systems. S. aureus is also notorious for its ability to resist the arsenal of currently available antibiotics and dissemination of various multidrug-resistant S. aureus clones limits therapeutic options for a S. aureus infection. Recently, the development of anti-virulence therapeutics that neutralize S. aureus toxins or block the pathways that regulate toxin production has shown potential in thwarting the bacteria's acquisition of antibiotic resistance. In this review, we provide insights into the regulation of S. aureus toxin production and potential anti-virulence strategies that target S. aureus toxins.

Lok JB (2007) WormBook "Strongyloides stercoralis: a model for translational research on parasitic nematode biology."

Lok JB

[WormBook, 2007]

Because of their free-living life cycle alternatives, Strongyloides and related nematode parasites may represent the best models for translating C. elegans science to the study of nematode parasitism. S. stercoralis, a significant pathogen of humans, can be maintained in laboratory dogs and gerbils. Biosafety precautions necessary for work with S. stercoralis, though unfamiliar to many C. elegans researchers, are straightforward and easily accomplished. Although specialized methods are necessary for large-scale culture of the free-living stages of S. stercoralis, small-scale cultures for experimental purposes may be undertaken using minor modifications of standard C. elegans methods. Similarly, the morphological similarities between C. elegans and the free-living stages of S. stercoralis allow investigational methods such as laser cell ablation and DNA transformation by gonadal microinjection to be easily adapted from C. elegans to S. stercoralis. Comparative studies employing these methods have yielded new insights into the neuronal control of the infective process in parasites and its similarity to regulation of dauer development in C. elegans. Furthermore, we have developed a practical method for transient transformation of S. stercoralis with vector constructs having various tissue- and cell-specific expression patterns and have assembled these into a modular vector kit for distribution to the community.

Savel J et al. (2006) Ann Pharm Fr "[A Nematode Nobel Prize: Caenorhabditis elegans]"

Savel J, Clostre F

[Ann Pharm Fr, 2006]

The Nematode Caenorhabditis elegans (C. elegans) is an established model increasingly used for studying human disease pathogenesis. C. elegans models are based on the mutagenesis of human disease genes conserved in this Nematode or on the transgenesis with disease genes not conserved in C. elegans. Genetic examinations will give new insights on the cellular and molecular mechanisms that are altered in some neurodegenerative diseases like Duchenne''s muscular dystrophy, Huntington''s disease and Alzheimer''s disease. C. elegans may be used for primary screening of new compounds that may be used as drugs in these diseases.

Portman DS et al. (2004) Mol Cell "Toward the computable transcriptome."

Bohmann D, Portman DS

[Mol Cell, 2004]

Applying a combination of innovative approaches to understanding neuronal gene regulation in C. elegans, an article in the latest Developmental Cell (Wenick and Hobert, 2004) gives hope that reading the genome''s transcriptional regulatory code may one day be possible.

Gutierrez-Zepeda A et al. (2004) Front Biosci "Testing the amyloid toxicity hypothesis of Alzheimer's disease in transgenic Caenorhabditis elegans model."

Gutierrez-Zepeda A, Luo Y

[Front Biosci, 2004]

Alzheimer''s disease (AD) is affecting more people every year due to the increase in elderly population. This disease is characterized by senior plaques, containing aggregated amyloid beta peptide (A beta), and neurofibrillary tangles in the AD brains. The A beta depositions are thought to increase in cellular oxidative stress, which subsequently produces neuronal cell death in the patient s brain, causing loss of memory and, in the latter stages, dementia. Diverse models have been established to test this, "Amyloid Toxicity Hypothesis of AD". Among these, the use of the nematode Caenorhabditis elegans has some advantages. This invertebrate has its entire genome known, as well as numerous gene homologues to those seen in humans. In relationship with the cell model, the nematode gives the benefit of an organismal view of the disease. The nematode''s short life span proves useful, when compared with that of mice, allowing mechanistic studies of the disease and pharmacological treatments. Alongside with other laboratories, we have used this in vivo model to correlate the Abeta expression with its toxicity through the observance of the organism''s behavior to provide a better understanding of the cellular processes underlining AD.

Schmidt E et al. (2007) Neurodegener Dis "Caenorhabditis elegans as a model system for Parkinson's disease."

Baumeister R, Schmidt E, Seifert M

[Neurodegener Dis, 2007]

Parkinson''s disease (PD) is one of the most common age-related neurodegenerative diseases that is characterized by selective loss of dopaminergic neurons. Despite recent findings from mammalian model systems, molecular mechanisms of the pathophysiology are poorly understood. Given the high conservation of molecular pathways from invertebrates to mammalians, combined with technical advantages, such as high-throughput approaches, Caenorhabditis elegans represents a powerful system for the identification of factors involved in neurodegeneration. In this review we describe that C. elegans can be used to advance our understanding of the genetic mechanisms implicated in these disorders. Copyright (c) 2007 S. Karger AG, Basel.

Richie CT et al. (2005) Curr Biol "Chromosome segregation: Aurora B gets Tousled."

Golden A, Richie CT

[Curr Biol, 2005]

Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode''''s Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during