Gruber J et al. (2017) Cell "Microbiome and Longevity: Gut Microbes Send Signals to Host Mitochondria."

Kennedy BK, Gruber J

[Cell, 2017]

The microbiome has emerged as a major determinant of the functioning of host organisms, affecting both health and disease. Here, Han etal. use the workhorse of aging research, C.elegans, to identify specific mechanisms by which gut bacteria influence mitochondrial dynamics and aging, a first steptoward analogous manipulations to modulate human aging.

Amrit FRG et al. (2017) J Vis Exp "Transcriptomic Analysis of C. elegans RNA Sequencing Data Through the Tuxedo Suite on the Galaxy Project."

Ghazi A, Amrit FRG

[J Vis Exp, 2017]

Next generation sequencing (NGS) technologies have revolutionized the nature of biological investigation. Of these, RNA Sequencing (RNA-Seq) has emerged as a powerful tool for gene-expression analysis and transcriptome mapping. However, handling RNA-Seq datasets requires sophisticated computational expertise and poses inherent challenges for biology researchers. This bottleneck has been mitigated by the open access Galaxy project that allows users without bioinformatics skills to analyze RNA-Seq data, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID), a Gene Ontology (GO) term analysis suite that helps derive biological meaning from large data sets. However, for first-time users and bioinformatics' amateurs, self-learning and familiarization with these platforms can be time-consuming and daunting. We describe a straightforward workflow that will help C. elegans researchers to isolate worm RNA, conduct an RNA-Seq experiment and analyze the data using Galaxy and DAVID platforms. This protocol provides stepwise instructions for using the various Galaxy modules for accessing raw NGS data, quality-control checks, alignment, and differential gene expression analysis, guiding the user with parameters at every step to generate a gene list that can be screened for enrichment of gene classes or biological processes using DAVID. Overall, we anticipate that this article will provide information to C. elegans researchers undertaking RNA-Seq experiments for the first time as well as frequent users running a small number of samples.

Dent JA et al. (1998) Mech Dev "Post-embryonic expression pattern of C. elegans let-60 ras reporter constructs."

Dent JA, Han M

[Mech Dev, 1998]

let-60 ras plays roles in the differentiation of several C. elegans tissues (Yochem, J., Sundaram, M., Han, M., 1997. Ras is required for a limited number of cell fates and not for general proliferation in Caenorhabditis elegans. Mol. Cell. Biol. 17, 2716-2722). To understand the transcriptional regulation of ras and to identify new functions for ras in development, we examined expression patterns of let-60::lacZ and let-60::GFP reporter constructs in C. elegans hermaphrodites. Fusion constructs were expressed in vulval precursor cells, sex myoblasts and in cell lineages of the somatic gonad, germline cells (GFP construct only), hypodermis, muscle and nervous system.

(2021) Development "The people behind the papers - Brandon Carpenter and David Katz."

[Development, 2021]

A dynamic pattern of histone methylation and demethylation controls gene expression during development, with some processes such as formation of the zygote involving large-scale reprogramming of methylation states. A new paper in Development investigates how inherited histone methylation regulates developmental timing and the germline/soma distinction in <i>Caenorhabditis elegans</i> To hear more about the story we caught up with first author and postdoctoral researcher Brandon Carpenter, and his supervisor David Katz, Associate Professor in the Department of Cell Biology at Emory University School of Medicine in Atlanta, Georgia.

Darnet S et al. (2019) J Lipid Res "Worming our way toward multiple evolutionary origins of convergent sterol pathways."

Fliesler SJ, Schaller H, Darnet S

[J Lipid Res, 2019]

Sterols represent one of the most ubiquitous and diverse classes of biological molecules derived from the common precursor mevalonic acid. While there are thematically similar modes by which various organisms synthesize sterols, there also are some unique twists in the pathways by which such organisms produce sterols as well as differences in the chemical nature of the dominant resident sterol present at steady-state in a given organism or cell type. In this issue of Journal of Lipid Research, David Nes and colleagues (Zhou et al. (1)) present a compelling and novel story, wherein they have elucidated a previously unknown alternative biosynthetic pathway utilized by nematodes (roundworms, of which Caenorhabditis elegans is an exemplar) to generate C4methyl sterols. This provides an evolutionary &quot;missing link&quot; along the continuum from prokaryotes to eukaryotes or eventually a singular divergent evolution of roundworms with regard to diversification of sterols and the metabolic routes accessible to them to achieve such diversity.

Smith ST et al. (1996) Development "A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo."

Smith ST, Jaynes JB

[Development, 1996]

The engrailed homeoprotein is a dominantly acting or ''active'' transcriptional repressor both in cultured cells and in vivo. When retargeted via a homeodomain swap to the endogenous fushi tarazu gene (ftz), it actively represses it, resulting in a ftz mutant phenocopy. We have mapped functional regions of engrailed using this in vivo repression assay. In addition to a region containing an active repression domain identified in cell culture assays (K. Han and J. L. Manley (1993) EMBO J. 12, 2723-2733), we find that two evolutionarily conserved regions contribute to activity. The one of these that does not flank the HD is particularly crucial to repression activity in vivo. We find that this domain is present not only in all engrailed-class homeoproteins but also in all known members of several other classes, including goosecoid, Nk1, Nk2 and msh. Thus engrailed''s active repression function in vivo is dependent on a highly conserved interaction that was established early in the evolution of the homeobox gene superfamily. We further show using rescue transgenes that the widely conserved in vivo repression domain is required for the normal function of engrailed in the embryo.

Lok JB et al. (1992) Parasitol Today "Animal models for the study of immunity in human filariasis."

Lok JB, Abraham D

[Parasitol Today, 1992]

A major challenge to the development of vaccines against human lymphatic filariasis and onchocerciasis is to direct the immune response toward elimination of the early, prepathogenic larval stages and away from responses that mediate pathology. In this review, James Lok and David Abraham discuss the various animal models that have been used to investigate the pathways leading to immunity, immunological tolerance and chronic pathology in these diseases. Owing to the strict host specificities of the human-dwelling filariae, no single model serves to duplicate exactly all these aspects. Nevertheless, it has been possible to demonstrate a protective immune response invoked by and directed against incoming third-stage larvae of both lymphatic and skin-dwelling filariae. The fact that subsets of the sequelae of human filarial infection can be duplicated in animal systems should also aid in unravelling the mechanisms determining the course of infection and in ensuring that vaccine candidates do not produce an inappropriate immunopathological response. A proposed scheme for using animal models in screening candidates for a vaccine against Onchocerca volvulus is presented.

O'Hara L et al. (2006) J Biol Chem "Control of phospholipid synthesis by phosphorylation of the yeast lipin Pah1p/Smp2p Mg2+-dependent phosphatidate phosphatase."

Han GS, O'Hara L, Grimsey N, Carman GM, Siniossoglou S, Peak-Chew S

[J Biol Chem, 2006]

Phosphorylation of the conserved lipin Pah1p/Smp2p in Saccharomyces cerevisiae was previously shown to control transcription of phospholipid biosynthetic genes and nuclear structure by regulating the amount of membrane present at the nuclear envelope (Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S., and Siniossoglou, S. (2005) EMBO J. 24, 1931-1941). A recent report identified Pah1p as a Mg2+-dependent phosphatidate (PA) phosphatase that regulates de novo lipid synthesis (Han G.-S., Wu, W. I., and Carman, G. M. (2006) J. Biol. Chem. 281, 9210-9218). In this work we use a combination of mass spectrometry and systematic mutagenesis to identify seven Ser/Thr-Pro motifs within Pah1p that are phosphorylated in vivo. We show that phosphorylation on these sites is required for the efficient transcriptional derepression of key enzymes involved in phospholipid biosynthesis. The phosphorylation-deficient Pah1p exhibits higher PA phosphatase-specific activity than the wild-type Pah1p, indicating that phosphorylation of Pah1p controls PA production. Opi1p is a transcriptional repressor of phospholipid biosynthetic genes, responding to PA levels. Genetic analysis suggests that Pah1p regulates transcription of these genes through both Opi1p-dependent and -independent mechanisms. We also provide evidence that derepression of phospholipid biosynthetic genes is not sufficient to induce the nuclear membrane expansion shown in the pah1delta cells.

Winkenbach LP et al. (2019) RNA Biol "Todos Santos small RNA symposium."

Claycomb JM, Doser R, Pasquinelli AE, Winkenbach LP, Reed KJ, Phillips CM

[RNA Biol, 2019]

Worm biologists from the United States, Canada, and the United Kingdom gathered at the Colorado State University Todos Santos Center in Baja California Sur, Mexico, April 3-5, 2019 for the Todos Santos Small RNA Symposium. Meeting participants, many of whom were still recovering from the bomb cyclone that struck a large swath of North America just days earlier, were greeted by the warmth and sunshine that is nearly ubiquitous in the sleepy seaside town of Todos Santos. With only 24 speakers, the meeting had the sort of laid-back vibe you might expect amongst the palm trees and ocean breeze of the Pacific coast of Mexico. The meeting started with tracing the laboratory lineages of participants. Not surprisingly, the most common parental lineages represented at the meeting were Dr. Craig Mello, Dr. Gary Ruvkun, and Dr. Victor Ambros, whom, together with Dr. Andy Fire and Dr. David Baulcombe, pioneered the small RNA field. In sad irony, on the closing day of the meeting, participants were met with the news of Dr. Sydney Brenner's passing. By establishing the worm, <i>Caenorhabditis elegans</i>, as a model system Dr. Brenner paved the way for much of the research discussed here.

Fatima S et al. (2018) Protein J "C.el Phosphatome: A Catalogue of Actual and Pseudo Phosphatases Based on In-Silico Studies in Caenorhabditis elegans."

Shukla S, Fatima S, Nazir A

[Protein J, 2018]

Phosphatases are well known to carry out important functions via counter activity of kinases and they serve as mechanism for dephosphorylating the monophosphate esters from the phosphorylated serine, threonine, tyrosine and histidine residues. The biological relevance of phosphatases could be explored further employing newer technologies and models. Caenorhabditis elegans is a powerful genetic model system that bears significant homology with humans, hence providing with a precious tool towards studying important signalling pathways. We carried out the present study to catalogue the C. elegans protein phosphatome, referred here as 'C.el phosphatome' and annotated the corresponding dataset. We further classified these phosphatases based on presence of catalytic conserved motif; GDxHG, GDxVDRG, GNHE, RxxD, DGxxG, DG, GxxDN for Ser/Thr phosphatases, HC(x)5 R for tyrosine phosphatases and DxDxT/V for aspartate based phosphatases. Bioinformatics tool DAVID was employed to decipher the biological relevance of phosphatases. Our findings show Ser/Thr phosphatases (114), Tyr phosphatases (121) and Asp phosphatases (0) in C. elegans genome based on the hallmark sequence identification. Amongst them, 34 and 57 Ser/Thr and Tyr phosphatases respectively contain the catalytic motif. This catalogue offers a precious tool for further studies towards understanding important biological processes and disease conditions.