Joshua M Stuart et al. (2003) International Worm Meeting "Discovering conserved pathways and core molecular machinery on a global scale."

Stuart Kim, Joshua M Stuart, Daphne Koller, Eran Segal

[International Worm Meeting, 2003]

The genome projects have paved the way for new genome-wide functional studies on several organisms. We can now use the rich supply of DNA microarray data to find expression patterns that reflect physiologically meaningful relationships. We have developed a computational technique for identifying conserved co-expression patterns in multiple organisms. Co-expression that represents a functionally-relevant coupling between two genes will confer a selective advantage to the organism and hence be selected over the course of evolution while irrelevant co-expression will be lost. We constructed a multi-species expression network combining microarray data from over 3000 microarray experiment from four evolutionarily distant organisms H. sapiens, S. cerevisiae, C. elegans, and D. melanogaster. We found over 10,000 examples of pairs of genes that are strongly co-expressed in microarray data from at least two organisms. These gene correlations form a network revealing many relationships between genes involved in ancient pathways and complexes, spanning several cellular and multicellular core processes. The network includes over 300 genes that encode novel proteins, and we can assign potential functions to these genes based on their co-expression with genes of known function. We are in the process of making the network available as a resource for the academic community.

McCombie WR et al. (1992) Worm Breeder's Gazette "Identification of C. elegans Genes Encoding ProteinsSimilar to the Valosin/Tat Binding Protein Family"

Kelley JM, Utterback TR, McCombie WR, Fitzgerald MG, Fields CA

[Worm Breeder's Gazette, 1992]

The human tat binding protein (tbp-1 )is a negative modulator of HIV transactivation which acts by binding to the Tat transactivating protein (Nelbock, et al, Science, 248: 1650-1653). Human tbp-1 shows similarity to a number of proteins involved in disparate functions in yeast and other organisms, which include the valosin containing protein and the yeast protein CDC48 p,which is involved in cell cycle control (Frohlich, et al, J. Cell. Biol. 114: 443-453 (1991)). While some regions of these proteins show a high degree of similarity to tbp-1 ,the sequence of tbp-1 is quite different from the other members of the family in the carboxyl terminal region. We have isolated two cDNAs that are members of this gene family from an embryonic library. One of these, CEESH69 ,appears most closely related to the CDC48 ptype members of the family based on the sequence of the clone at the 3' end. However, the other clone, CEESA17 ,appears to encode a protein that is strikingly similar to tbp-1 ,including the carboxyl terminal region unique to tbp-1 .The alignments of both proteins are shown below. We are currently mapping and sequencing these clones and will be characterizing them in more detail. Alignment of a translation of the EST from the 3' end of CEESH69 with the 806 amino acid porcine valosin containing protein (Koller and Brownstein, Nature 325: 542-545 (1987)) [See Figure 1]. Alignment of a translation of the EST from the 3' end of clone CEESA17 with the 404 amino acid tbp-1 [See Figure 2}.

Qiao Y et al. (2014) PLoS One "Full toxicity assessment of Genkwa Flos and the underlying mechanism in nematode Caenorhabditis elegans."

Qiao Y, Ruan Q, Duan J, Sun L, Chen Y, Wang D, Wu Q, Wang M, Zhao Y

[PLoS One, 2014]

Genkwa Flos (GF), the dried flower bud from Daphne genkwa Sieb. et Zucc. (Thymelaeaceae), is a well-known and widely used traditional Chinese medicine. However, we know little about the in vivo mechanism of GF toxicity. Nematode Caenorhabditis elegans has been considered as a useful toxicity assay system by offering a system best suited for asking the in vivo questions. In the present study, we employed the prolonged exposure assay system of C. elegans to perform the full in vivo toxicity assessment of raw-processed GF. Our data show that GF exposure could induce the toxicity on lifespan, development, reproduction, and locomotion behavior. GF exposure not only decreased body length but also induced the formation of abnormal vulva. The decrease in brood size in GF exposed nematodes appeared mainly at day-1 during the development of adult nematodes. The decrease of locomotion behavior in GF exposed nematodes might be due to the damage on development of D-type GABAergic motor neurons. Moreover, we observed the induction of intestinal reactive oxygen species (ROS) production and alteration of expression patterns of genes required for development of apical domain, microvilli, and apical junction of intestine in GF exposed nematodes, implying the possible dysfunction of the primary targeted organ. In addition, GF exposure induced increase in defecation cycle length and deficits in development of AVL and DVB neurons controlling the defecation behavior. Therefore, our study implies the usefulness of C. elegans assay system for toxicity assessment from a certain Chinese medicine or plant extract. The observed toxicity of GF might be the combinational effects of oxidative stress, dysfunction of intestine, and altered defecation behavior in nematodes.

Boxem, Mike (2009) International Worm Meeting "Mapping the protein interaction network that controls cell polarity."

Boxem, Mike

[International Worm Meeting, 2009]

Interactions between proteins are a key component of most or all biological processes. A key challenge in biology is to generate comprehensive and accurate maps (interactomes) of all possible protein interactions in an organism. This will require iterative rounds of interaction mapping using complementary technologies, as well as technological improvements to the approaches used. For example, we recently developed a novel yeast two-hybrid approach that adds a new level of detail to interaction maps by defining interaction domains(1). Currently, I am working to generate an interaction map of proteins involved in controlling cell polarity in C. elegans to improve our understanding of the molecular mechanisms that establish and maintain cell polarity in multicellular organisms. I will combine two fundamentally different interaction mapping techniques: the yeast two-hybrid system (Y2H) and affinity purification/mass spectrometry (AP/MS). This will provide more detail by identifying both direct interactions between pairs of proteins by Y2H, and the composition of protein complexes by AP/MS. Moreover, interactions missed by one technology may be detected by the other, leading to a more complete interaction map. I will integrate the physical interactions with phenotypic characterizations. To this end I will systematically characterize the interaction network in vivo using two distinct models of polarity: asymmetric division of the one-cell embryo, and stem-cell-like divisions of a multicellular epithelium (in collaboration with M. Wildwater and S. van den Heuvel). M. Boxem, Z. Maliga, N. Klitgord, N. Li, I. Lemmens, M. Mana, L. de Lichtervelde, J. D. Mul, D. van de Peut, M. Devos, N. Simonis, M. A. Yildirim, M. Cokol, H. L. Kao, A. S. de Smet, H. Wang, A. L. Schlaitz, T. Hao, S. Milstein, C. Fan, M. Tipsword, K. Drew, M. Galli, K. Rhrissorrakrai, D. Drechsel, D. Koller, F. P. Roth, L. M. Iakoucheva, A. K. Dunker, R. Bonneau, K. C. Gunsalus, D. E. Hill, F. Piano, J. Tavernier, S. van den Heuvel, A. A. Hyman, and M. Vidal, A protein domain-based interactome network for C. elegans early embryogenesis. Cell, 2008. 134(3): p. 534-545. .