Lev, I. et al. (2015) International Worm Meeting "Transgenerational response to a challenging environment in C. elegans."

Lev, I., Rechavi, O.

[International Worm Meeting, 2015]

Over a century ago August Weismann showed in his experiments that offspring of tail-mutilated mice grow morphologically normal tails. From these experiments and others he concluded that acquired phenotypic changes are not heritable, a well-known principle termed "The Weismann barrier". Recent studies suggest that in some cases the Weismann barrier can be breached and that certain acquired traits can be transferred to ensuing generations.In response to different environmental challenges, such as viral infection or starvation, C. elegans synthesize and transgenerationally transmit small RNAs that either protect their descendants from the infecting virus or enhance their life-span, respectively. In this work we show an additional environmental cue that changes the morphology of C. elegans progeny, possibly preparing them for adverse conditions associated with the environmental challenge.

Liu, Z. et al. (2017) International Worm Meeting "Sulfolipids drive C. elegans defensive responses to a predator."

Pribadi, A., Srinivasan, J., Liu, Z., Curran, K., Leinwand, S., Schroeder, F., Bose, N., Chalasani, S., Tong, A., Chute, C., Kariya, M.

[International Worm Meeting, 2017]

Animals respond to predator threats by implementing characteristic behavioural and physiological changes, but it is not known how the underlying neuronal ensembles process these threats. The simple, well-defined nervous system of the nematode, Caenorhabditis elegans facilitates uncovering conserved principles in neuronal processing. Here we show that C. elegans responds to excretions from a nematode predator, Pristionchus pacificus with instantaneous escape behaviour and a prolonged reduction of oviposition. Chemical analysis of the P. pacificus exo-metabolome revealed a series of novel sulfated lipids that instruct these C. elegans responses. These sulfolipids are specific to the predator and originate from a biosynthetic pathway that ties into endocrine signalling required for predacious behavior.

Consortium Wormbase et al. (2000) West Coast Worm Meeting "From ACeDB to a more complete and usable database"

Consortium Wormbase, Foltz NL, Schwarz EM, Sternberg PW

[West Coast Worm Meeting, 2000]

We briefly describe the current status and plans for WormBase, initially an extension of the existing ACeDB database with a new user interface. The WormBase consortium includes the team that developed ACeDB (Richard Durbin and colleagues at the Sanger Centre; Jean Thierry-Mieg and colleagues at Montpellier); Lincoln Stein and colleagues at Cold Spring Harbor, who developed the current web interface for WormBase; and John Spieth and colleagues at the Genome Sequencing Center at Washington University, who along with the Sanger Centre team, continue to annotate the genomic sequence. The Caltech group will curate new data including cell function in development, behavior and physiology, gene expression at a cellular level, and gene interactions. Data will be extracted from the literature, as well as by community submission. We look forward to providing the C. elegans and broader research community easy access to vast quantities of high quality data on C. elegans. Also, we welcome your suggestions and criticism at any time. WormBase can be accessed at www.wormbase.org.

Joseph Coolon et al. (2006) Development & Evolution Meeting "C. elegans genes differentially expressed in response to a soil bacterial environment"

Kenneth Jones, Timothy Todd, Michael Herman, Joseph Coolon

[Development & Evolution Meeting, 2006]

The free living soil nematode Caenorhabditis elegans has been cultured in the lab for over four decades on agar plates feeding almost exclusively on E. coli OP50, which served as their source of nutrition as well as their immediate environment. Almost all that is known about gene function in C. elegans has been determined in this environment. Yet, many of the genes in C. elegans genome have not been assigned a function. It seems reasonable that at least some proportion of the genes of unknown function evolved to allow C. elegans to respond to its natural environment. As part of a larger project to discover gene functions required for ecological interactions, we are conducting parallel studies examining changes in nematode diversity in response to environmental perturbations in the field 1, and using C. elegans to model those environmental perturbations in the lab. We identified several bacterial isolates from Konza Prairie (near Manhattan, KS ) soils, of which Micrococcus luteus was the most abundant of the culterable bacterial taxa. We used cDNA microarrays to identify genes involved in nematode responses to different bacterial diet or environments. We identified 142 genes with significant changes in expression levels in response to growth on M. luteus versus growth on E. coli. Mutant alleles were available for five of these genes. In order to examine the contribution of these genes to nematode fitness in different bacterial environments, we have examined brood sizes. Four mutants displayed statistically significant reduction in brood size when grown on M. luteus. Furthermore, mutant phenotypes have not been reported for two of these genes. We are extending these findings by analyzing C. elegans responses to other soil bacteria that were isolated in association with nematodes from Konza prairie, including Bacillus megaterium and Pseudomonas sp., also using cDNA microarrays. These comparisons have also identified genes specifically induced in response to growth on soil bacteria. Thus not only are the expression of specific genes induced in response to a change in environment, but some of these genes contribute to fitness traits. These results demonstrate that assessing C. elegans gene functions in more natural environments can allow new functions to be assigned to genes of unknown function.

Powell, Jennifer (2015) International Worm Meeting "Crowd-sourcing worm genetics to bring novel research to a large undergraduate lab class."

Powell, Jennifer

[International Worm Meeting, 2015]

At Gettysburg College, we have experienced the well-known benefits of introducing students to authentic research early in their college career through expanded support of apprentice-style student-faculty research and the development of several intensive first-year course-based research experiences. Both of these models are highly effective; however, they are very costly in terms of necessary financial support and faculty time, and therefore reach a limited number of students. Genetics is a required course for the Biology, Biochemistry and Molecular Biology, and Health Science (B.S.) majors and is typically taken by sophomores. We developed a research-based lab experience for this course and piloted it during the fall semester with 34 students in 2 lab sections. Our goals included providing an authentic experience that allowed students to experience the reality of science, to address meaningful novel scientific questions using current techniques and equipment, and to generate publishable data. Key to the success of the lab was selecting a project that benefitted from rather than was hindered by a large number of student researchers. By crowd-sourcing an RNAi screen, we were collectively able to screen a large number of clones with built-in redundancy to increase the quality of the data generated by novice undergraduates. Students felt ownership of and responsibility for the clones they were assigned, but overseeing the 17 pairs of students was manageable because they were each learning and eventually mastering the same set of techniques. There are certainly challenges to adapting a large lab course for research, including the technical inexperience of the students, limited equipment, and limited financial resources. We will discuss how we met these challenges, and, whenever possible, tried to turn them into assets. .

Miller DM et al. (1989) International C. elegans Meeting "unc-2, -3, -4, the long march to a neurogenic mocus."

McGhee M, Peplinski S, Miller DM

[International C. elegans Meeting, 1989]

Zhang, Liangyu et al. (2021) International Worm Meeting "Meiotic cell cycle progression requires adaptation to a constitutive DNA damage signal"

Hollingsworth, Nancy, Stauffer, Weston, Wang, John, Zhang, Liangyu, Dernburg, Abby, Ziesel, Andrew, Yu, Zhouliang

[International Worm Meeting, 2021]

Defects in crossover formation lead to chromosome missegregation during meiosis. The mechanisms that ensure crossover formation and coordinate crossover designation with meiotic progression remain poorly understood. In C. elegans, defects in homolog pairing, synapsis, or recombination delay meiotic progression and prolong the activity of CHK-2, a meiosis-specific ortholog of the canonical DNA damage checkpoint kinase that plays essential roles during early prophase. We have now found that CHK-2 activity is both necessary and sufficient to inhibit crossover designation. CHK-2 is normally inactivated at mid-pachytene, but persists under conditions that prevent or delay the establishment of crossover precursors on one or more chromosomes. The pathway that mediates CHK-2 inactivation in wild-type or crossover-deficient conditions has not been established. We find that CHK-2 is inactivated and destabilized through inhibitory phosphorylation by Polo-like kinases (PLKs), a mechanism previously implicated in adaptation to DNA damage checkpoint signaling in proliferating cells. Recruitment to the synaptonemal complex and establishment of crossover precursors activate PLKs to phosphorylate CHK-2 and drive meiotic progression. Additionally, we find that stepwise reduction of CHK-2 activity enables the rapid, concerted designation of crossover sites on all chromosomes at mid-pachytene. These findings reveal that a key transition during the meiotic cell cycle occurs through adaptation to a "constitutive" DNA damage response pathway that is implemented at meiotic entry. Evidence from budding yeast suggests that the Polo-like kinase Cdc5 may similarly promote inactivation and degradation of Mek1, a CHK-2 ortholog, and data from mice are also consistent with such a mechanism. Our work further clarifies the signaling network that coordinates chromosome dynamics, double-strand break formation, and recombination during meiotic prophase.

Takeshi Ishihara et al. (2003) International Worm Meeting "HEN-1 specifically binds to a subpopulation of C.elegans primary culture cells."

Isao Katsura, Takeshi Ishihara

[International Worm Meeting, 2003]

Integration of two sensory signals is one of the most fundamental step in the informational processing in the neural circuit. To elucidate its molecular mechanisms, we study mutants defective in the interaction of two sensory signals. Among those, hen-1 mutant animals prefer avoidance of Cu2+ ion to chemotaxis to diacetyl, although they show normal response to Cu2+ ion or to diacetyl. In addition, hen-1 shows defects in behavioral plasticity after conditioned with NaCl and starvation, and with temperature and starvation. The positional cloning reveals that the hen-1 gene encodes a secretory protein with a LDL receptor motif. HEN-1 protein is localized in the axons of ASE and AIY neurons. The expression of HEN-1 by cell type specific promoters and a heatshock promoter in the hen-1 mutant reveals that HEN-1 protein functions cell-non-autonomously in the mature nervous system. These results suggests that HEN-1 is a neuromodulator for regulating the sensory integration and neuronal plasticity. To elucidate how HEN-1 regulates neuronal modulation, we are searching a binding protein for HEN-1 protein. The HEN-1-alkaline phosphatase fusion protein (HEN-1-AP) expressed in HEK293 cells was secreted to the medium. To identify the receptor for the HEN-1, we analyzed whether HEN-1-AP can bind to C.elegans cells. HEN-1-AP bound a subpopulation of cell surface of the C. elegans primary culture cells, but alkaline phosphatase did not. This result indicates that a specific receptor for HEN-1 exists in C.elegans. Therefore, we are screening an expression cDNA library of the C. elegans primary culture cells by using this binding assay system.

Pribadi, A. et al. (2017) International Worm Meeting "A family of novel sulfolipids drives C. elegans defensive responses to a predator."

Liu, Z., Schroeder, F., Srinivasan, J., Pribadi, A., Chalasani, S., Kariya, M.

[International Worm Meeting, 2017]

Animals discover predators in their environment and execute appropriate behaviors to increase survival. We investigated Caenorhabditis elegans' responses to a nematode predator, Pristionchus pacificus. Upon detecting P. pacificus excretions, C. elegans responded with behaviors on multiple timescales - an instantaneous escape behavior and a prolonged reduction in egg laying. In collaboration with the Schroeder lab (Cornell University), we used an activity guided fractionation approach to identify the relevant signals. We found that P. pacificus specifically produces a family of novel sulfated lipids that drive both C. elegans responses. Using cell ablations and calcium imaging, we found that a third of the C. elegans amphid sense organ (ASI, ASJ, ASH and ADL neurons) is involved in detecting predator excretions. Exploiting genetic mutants, we show that cyclic nucleotide gated and transient receptor potential channels function in distinct subsets of neurons to drive C. elegans responses. Finally, we show that a human anti-anxiety drug, Zoloft attenuates C. elegans responses to the predator. These studies show that signaling pathways for processing external threats are likely conserved from worms to mammals. Animals discover predators in their environment and execute appropriate behaviors to increase survival.

Danielle L Huffman et al. (2003) International Worm Meeting "How C. elegans responds to a pore-forming toxin from Bacillus thuringiensis"

Raffi V Aroian, Danielle L Huffman

[International Worm Meeting, 2003]

Bacillus thuringiensis(Bt) is a spore-forming soil bacterium that produces crystal (Cry) toxins with insecticidal or nematicidal activities. Different strains of Bt produce different Cry toxins, each with its own range of invertebrate targets. Once a crystal is ingested by a susceptible host, the Cry proteins are solubilized and activated by the intestinal proteases. Proteolytically-activated toxin can then bind to receptors on the apical surface of the intestine, insert into the membrane and form pores in the lipid bilayer. The events that occur downstream of pore formation, and how these events eventually lead to the death of the host, remain unclear. Caenorhabditis elegans is susceptible to a short list of known Bt toxins, including Cry5B. We are using Affymetrix gene chips to uncover the details of how C. elegans responds to Cry5B at the transcriptional level after 0, 1, 2, 4 and 8 hours of toxin exposure. We have now repeated this full time-course and find that after just one hour of toxin feeding, 283 genes meet a two-fold level of induction on both replicates. By eight hours, this number is increased to 886 genes. Overall, we have identified more than 2,000 genes that are at least 2-fold over or under expressed in the presence of E. coli produced Cry5B toxin. Some of these genes may be regulated by the C. elegans host in an effort to defend against toxin activity. Other genes may be regulated in response to toxin and aid the processes that lead to death. One up-regulated gene, sek-1, encodes the C. elegans homolog of the mammalian MAP kinase kinase, MKK6. Previous work has identified this gene, and other members of the p38 MAP kinase pathway, as an important player in mammalian and worm defense against bacterial pathogens (Kim et. al., Science 2002 and Aballay et. al., Current Biology 2003). Our findings, as I will discuss, potentially broaden our view of the role of this pathway to include not only defense against a bacterium but also against a bacterial toxin. We are now using RNA interference to further uncover which Cry5B responsive genes play a functional role in pathogenesis. Those genes that contribute to defense (like sek-1) should mutate to a hypersensitive phenotype. Genes that contribute to intoxication should mutate to a hyper-resistant phenotype. Identifying which genes shape this process could lead to insights into how the toxin actually kills, how the host attempts to defend itself, and why this defense ultimately fails.