Temmerman L et al. (2011) Ann N Y Acad Sci "C. elegans homologs of insect clock proteins: a tale of many stories."

Temmerman L, Schoofs L, Bogaerts A, Husson SJ, Lindemans M, Janssen T, Beets I, Meelkop E

[Ann N Y Acad Sci, 2011]

As a consequence of the Earth's axial rotation, organisms display daily recurring rhythms in behavior and biochemical properties, such as hormone titers. The neuronal system controlling such changes is best studied in the fruit fly Drosophila melanogaster. In the nematode worm Caenorhabditis elegans, most homologs of these genes function in the heterochronic pathway controlling the (timing of) developmental events. Recent data indicate that in the worm at least one of the genes involved in developmental timing is also active in circadian rhythm control, thereby opening up new perspectives on a central (neuronal) timer interfering with many processes. Also, new neuropeptidergic clock homologs have been identified in nematodes, supporting the idea of a broad range of clock-regulated targets. We will describe the current knowledge on homologous clock genes in C. elegans with a focus on the recently discovered pigment dispersing factor gene homologs. Similarities between developmental and daily timing are discussed.

Driesschaert B et al. (2021) J Genet Genomics "Conditional gene expression in invertebrate animal models."

Temmerman L, Mergan L, Driesschaert B

[J Genet Genomics, 2021]

A mechanistic understanding of biology requires appreciating spatiotemporal aspects of gene expression and its functional implications. Conditional expression allows for (ir)reversible switching of genes on or off, with the potential of spatial and/or temporal control. This provides a valuable complement to the more often used constitutive gene (in)activation through mutagenesis, providing tools to answer a wider array of research questions across biological disciplines. Spatial and/or temporal control are granted primarily by (combinations of) specific promoters, temperature regimens, compound addition, or illumination. The use of such genetic tool kits is particularly widespread in invertebrate animal modelsbecause they can be applied to study biological processes in short time frames and on large scales, using organisms amenable to easy genetic manipulation. Recent years witnessed an exciting expansion and optimization of such tools, of which we provide a comprehensive overview and discussion regarding their use in invertebrates. The mechanism, applicability, benefits, and drawbacks of each of the systems, as well as further developments to be expected in the foreseeable future, are highlighted.

Beets I et al. (2013) Worm "Ancient neuromodulation by vasopressin/oxytocin-related peptides."

Schoofs L, Beets I, Janssen T, Temmerman L

[Worm, 2013]

Neuropeptidergic signaling is widely adopted by animals for the regulation of physiology and behavior in a rapidly changing environment. The vasopressin/oxytocin neuropeptide family originates from an ancestral peptide precursor in the antecedent of protostomian and deuterostomian animals. In vertebrates, vasopressin and oxytocin have both hormonal effects on peripheral target tissues, such as in the regulation of reproduction and water balance, and neuromodulatory actions in the central nervous system controlling social behavior and cognition. The recent identification of vasopressin/oxytocin-related signaling in C. elegans reveals that this peptidergic system is widespread among nematodes. Genetic analysis of the C. elegans nematocin system denotes vasopressin/oxytocin-like peptides as ancient neuromodulators of neuronal circuits involved in reproductive behavior and associative learning, whereas former invertebrate studies focused on conserved peripheral actions of this peptide family. Nematocin provides neuromodulatory input into the gustatory plasticity circuit as well as into distinct male mating circuits to generate a coherent mating behavior. Molecular interactions are comparable to those underlying vasopressin- and oxytocin-mediated effects in the mammalian brain. Understanding how the vasopressin/oxytocin family fine-tunes neuronal circuits for social behavior, learning and memory poses a major challenge. Functional conservation of these effects in nematodes and most likely in other invertebrates enables the development of future models to help answering this question.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Best AM et al. (2018) Cell Microbiol "Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts by Legionella pneumophilla."

Best AM, Kwaik YA

[Cell Microbiol, 2018]

Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-B, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.

Detienne G et al. (2018) Ageing Res Rev "Beyond ROS clearance: peroxiredoxins in stress signaling and aging."

De Haes W, Temmerman L, Van Bael S, Mergan L, Edwards SL, Detienne G

[Ageing Res Rev, 2018]

Antioxidants were long predicted to have lifespan-promoting effects, but in general this prediction has not been well supported. While some antioxidants do seem to have a clear effect on longevity, this may not be primarily as a result of their role in the removal of reactive oxygen species, but rather mediated by other mechanisms such as the modulation of intracellular signaling. In this review we discuss peroxiredoxins, a class of proteinaceous antioxidants with redox signaling and chaperone functions, and their involvement in regulating longevity and stress resistance. Peroxiredoxins have a clear role in the regulation of lifespan and survival of many model organisms, including the mouse, Caenorhabditis elegans and Drosophila melanogaster. Recent research on peroxiredoxins - in these models and beyond - has revealed surprising new insights regarding the interplay between peroxiredoxins and longevity signaling, which will be discussed here in detail. As redox signaling is emerging as a potentially important player in the regulation of longevity and aging, increased knowledge of these fascinating antioxidants and their mode(s) of action is paramount.

Van Assche R et al. (2015) J Mol Biol "Integrating -Omics: Systems Biology as Explored Through C. elegans Research."

Temmerman L, Boonen K, Schoofs L, Maes E, Van Assche R, Broeckx V, De Haes W

[J Mol Biol, 2015]

-Omics data have become indispensable to systems biology, which aims to describe the full complexity of functional cells, tissues, organs and organisms. Generating vast amounts of data via such methods, researchers have invested in ways of handling and interpreting these. From the large volumes of -omics data that have been gathered over the years, it is clear that the information derived from one -ome is usually far from complete. Now, individual techniques and methods for integration are maturing to the point that researchers can focus on network-based integration rather than simply interpreting single -ome studies. This review evaluates the application of integrated -omics approaches with a focus on Caenorhabditis elegans studies, intending to direct researchers in this field to useful databases and inspiring examples.

Lee SK et al. (2013) Int J Biochem Cell Biol "Dicarbonyl/l-xylulose reductase (DCXR): The multifunctional pentosuria enzyme."

Ahnn J, Lee SK, Son LT, Choi HJ

[Int J Biochem Cell Biol, 2013]

Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol. It also reduces highly reactive -dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. Enzymatic properties of DCXR from yeast, fungi and mammalian tissue extracts are extensively studied. Deficiency of the DCXR gene causes a human clinical condition called pentosuria and low DCXR activity is implicated in age-related diseases including cancers, diabetes, and human male infertility. While mice provide a model to study clinical condition of these diseases, it is necessary to adopt a physiologically tractable model in which genetic manipulations can be readily achieved to allow the fast genetic analysis of an enzyme with multiple biological roles. Caenorhabditis elegans has been successfully utilized as a model to study DCXR. Here, we discuss the biochemical properties and significance of DCXR activity in various human diseases, and the utility of C. elegans as a research platform to investigate the molecular and cellular mechanism of the DCXR biology.

Lv Z et al. (2015) Parasitol Res "Genome mining offers a new starting point for parasitology research."

Wu Z, Ji P, Li H, Cai Y, Zhang L, Luo S, Wang H, Lv Z

[Parasitol Res, 2015]

Parasites including helminthes, protozoa, and medical arthropod vectors are a major cause of global infectious diseases, affecting one-sixth of the world's population, which are responsible for enormous levels of morbidity and mortality important and remain impediments to economic development especially in tropical countries. Prevalent drug resistance, lack of highly effective and practical vaccines, as well as specific and sensitive diagnostic markers are proving to be challenging problems in parasitic disease control in most parts of the world. The impressive progress recently made in genome-wide analysis of parasites of medical importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini, Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis; cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium; protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L. donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis, Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti, Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been systematically covered in this review for a comprehensive understanding of the genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or endosymbiotic bacterial genomes of parasites, further valuable insight into parasite-host interactions and development of promising novel drug and vaccine candidates and preferable diagnostic tools, thereby underpinning the prevention and control of parasitic diseases.

Caffrey CR et al. (2018) PLoS Negl Trop Dis "Cysteine proteases as digestive enzymes in parasitic helminths."

Caffrey CR, Smith D, Dalton JP, Rebello KM, Goupil L

[PLoS Negl Trop Dis, 2018]

We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1-4]. Often, gut proteases are expressed as multigene families, as is the case with Fasciola [5] and Haemonchus [6], presumably expanding the range of substrates that can be degraded, not least during parasite migration through host tissues [5]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Finally, because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].