Chen, Chieh et al. (2015) International Worm Meeting "RIL-1 influences life span through suppression of mitochondrial electron transport chain in C. elegans."

Hsu, Ao-lin, Chen, Chieh

[International Worm Meeting, 2015]

It has been well documented that suppression of mitochondrial electron transport chain (ETC) during development extends life span of C. elegans. ril-1 was first identified as a longevity gene from the previous systematic genome-wide RNAi screen. Inhibition of ril-1 by RNAi can prolong life span in N2 by up to 72%. However, there was no known mammalian homolog or predicted function for this gene. Therefore, the mechanism by which RIL-1 influences lifespan remains unknown. Here, we aimed to further characterize this novel longevity gene. Our results suggest that the longevity effect of ril-1 knockdown works only when the inhibition initiated at the larva stage, similar to what has been observed in ETC gene mutants. Furthermore, inhibition of ril-1 by RNAi significantly lowers the O2 consumption. Finally, ril-1 knockdown animals exhibits several phenotypes that are also observed in ETC mutants, such as small body size, reduced reproduction, and delayed larval growth. Together, our findings strongly suggest that ril-1 may extend lifespan by suppressing ETC functions.

Chun-Chieh Chen et al. (2003) International Worm Meeting "Identification of RNAi Deficient (rde) Genes in C. elegans"

Craig Mello, Jennifer McCullough, Chun-Chieh Chen

[International Worm Meeting, 2003]

In C. elegans, the introduction of double-stranded RNA (ds-RNA) triggers sequence-specific gene silencing of the cognate mRNA termed RNA interference or RNAi. In order to elucidate the molecular mechanism of RNAi, our lab had performed genetic screens in search of genes required for this process. Mutants that have been characterized include rde-1 and rde-4 which are required for RNAi in all tissues (Tabara et al.); sid-1/rde-7, which has been proposed to function in the systemic RNAi (Winston et al.); and rrf-1/rde-9, which is required for RNAi in the somatic tissues (Sijen et al., and Conte et al., unpublished data). In a continuation of our efforts we have used a bacterial feeding strain expressing a fusion dsRNA that simultaneously targets both GFP and an essential gene. The desired RNAi deficient strains are viable and GFP positive. So far we have mutagenized 3 million haploid genomes and have recovered approximately 1,000 mutants from ~100 independent pools of mutagenized animals. These mutant strains include 30 independent alleles of rrf-1, 22 alleles of sid-1, 9 alleles of rde-1, as well as several new rdeloci. Several screens were open to the identification of temperature-sensitive mutants, and we have identified one ts allele of rrf-1 and one ts allele of what is most likely rde-6. In addition we have one ts strain that is RNAi resistant and also sterile at 25 degrees C.Progress in the genetic screens and in the cloning of specific new mutants will be presented.

Chun-Chieh Chen et al. (2002) East Coast Worm Meeting "Biochemical and genetic analysis of RNA interference in C. elegans"

Chun-Chieh Chen, Darryl Conte, Hiroaki Tabara, Craig Mello

[East Coast Worm Meeting, 2002]

RNAi is a post-transcriptional gene-silencing phenomenon induced by double-stranded RNAs. During RNAi, small-interfering RNAs (siRNAs) are formed and are thought to guide a nuclease complex in the destruction of target mRNAs. Interestingly, in C. elegans, the presence of a complementary target gene is required for siRNA accumulation and only the antisense siRNA strand is detectable by Northern analysis (Alla Grishok unpublished) This asymmetric accumulation of siRNA differs from results observed in Drosophila and plants and suggests that RNAi in C. elegans may include a surveillance step that ensures that only "useful" siRNAs are retained or amplified. Interestingly, RDE-4 has recently been shown to interact with RDE-1, DCR-1 and the trigger dsRNA, presumably forming a complex that functions to detect the presence of target mRNA (H. Tabara et al.). To further understand the mechanism of the target-dependent asymmetric accumulation of siRNAs, we performed northern analysis of wild-type and RNAi-deficient mutant worms exposed to pos-1 dsRNAs by feeding. We found that no siRNAs accumulates in dcr-1, rde-1 or rde-4 mutants. The absence of siRNA in rde-1 and rde-4 mutant backgrounds is consistent with the finding that these two proteins are required for the initiation of RNAi. Our findings also demonstrate for the first time that DCR-1 activity is indeed required for siRNA production in vivo. Consistent with a block in dsRNA processing we found that long-trigger dsRNA molecules accumulate in the dcr-1 mutants. Further biochemical tests are planned to examine the production of siRNAs by the DCR-1 complex. In addition, a new genetic screen will be carried out to identify additional rde mutants.

Chun-Chieh Chen et al. (2001) International C. elegans Meeting "Identification of New rde (RNAi deficient) mutants in C. elegans"

Hiroaki Tabara, Chun-Chieh Chen, Erbay Yigit, Craig C Mello

[International C. elegans Meeting, 2001]

In a number of organisms, the introduction of double-stranded RNA into cells causes the post-transcriptional silencing of the corresponding gene. This experimental phenomenon is called RNA interference (RNAi). We are particularly interested in molecular mechanism of this phenomenon. In order to elucidate the mechanism of RNAi we screened for rde (RNAi deficient) mutants and identified over 100 mutants. Previously, 30 of these mutants were analyzed and five complementation groups ( rde-1,-2,-3,-4 and mut-7 ) were identified. In this study, we have characterized 30 more mutants that define three new rde loci ( rde-5, -6, and -7 ). All three of these new mutants are primarily deficient in RNAi in the germline. The rde-5 and rde-6 mutants are similar to previous mutator class RNAi mutants such as mut-7 in that they exhibit transposon mobilization and increased frequency of males. The rde-7 locus differs from other germline specific RNAi mutants in that it does not exhibit any phenotypes other than RNAi resistance (For more on tissue specific RNAi mutants see the abstract by Conte et al.). rde-7 is on LGV and is defined by 5 alleles. rde-5 maps on LGV near unc-76 , and rde-6 maps on LG I near lin-11. While trying to use the Hawaiian strain CB4856 for single nucleotide polymorphism (SNP) mapping of the new rde- loci we discovered that this natural isolate of C. elegans is resistant to germline RNAi and contains at least two RNAi deficient loci, one that maps on LGI and one on LGIV. Further mapping studies are underway to determine if the Hawaii mutants represent new rde- loci. SNP mapping and rescue experiments are now underway to further define and clone the rde mutants.

Po MD et al. (2012) Neuron "Releasing the inner inhibition for axon regeneration."

Po MD, Calarco JA, Zhen M

[Neuron, 2012]

The adult mammalian central nervous system exhibits restricted regenerative potential. Chen etal. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.

Silverstein NJ et al. (2017) Immunity "Interleukin-17: Why the Worms Squirm."

Huh JR, Silverstein NJ

[Immunity, 2017]

IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen etal. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.

Artan M et al. (2016) Dev Cell "Heat FLiPs a Hormonal Switch for Longevity."

Lee SV, An SW, Artan M

[Dev Cell, 2016]

Temperature-sensing neurons in C.elegans reduce the life-shortening effects of high temperatures via steroid signaling. In this issue of Developmental Cell, Chen etal. (2016) elucidate the underlying mechanisms by which the transcription factor CREB induces the neuropeptide FLP-6 in the temperature-sensing neurons to counteract the life-shortening effects of high temperature.

Akin O et al. (2014) Cell "The shape of things to come."

Akin O, Zipursky SL

[Cell, 2014]

Surface receptors can link binding of ligands to changes in the actin-based cell cytoskeleton. Chia etal. and Chen etal. provide evidence for direct binding between the cytoplasmic tails ofreceptorsand the WAVE complex, a regulator of the actin nucleator Arp2/3 complex, which mighthelp to explain how environmental signals are translated into changes in morphology andmotility.

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan

Gourgou, Eleni et al. (2021) International Worm Meeting "C. elegans learning strategy in T-mazes and aging-related interventions"

Fretz, Abrielle, Gourgou, Eleni, Goettemoeller, Anne, Hsu, Ao-lin, Chen, Chieh

[International Worm Meeting, 2021]

C. elegans' ability to exhibit associative, non-associative and imprinted memory in the context of chemical stimuli is well studied. We provide evidence for a new type of associative learning, in which nematodes learn to associate food with a combination of proprioceptive cues and information on the structure of their surroundings (maze), perceived through mechanosensation. By using our custom-made Worm-Maze platform, we demonstrate that C. elegans young adults locate food in T-shaped mazes and, following that experience, learn to reach a specific maze arm. The observed learning is a food-triggered multisensory behavior, which requires mechanosensory and proprioceptive input, and utilizes cues about the structural features of nematodes' environment and their body actions. Our findings suggest that C. elegans use a type of response learning strategy to achieve learning in the maze, and that structural features of the environment play a role in the acquired learning. In addition, we show that the observed aging-driven decline C. elegans learning in the maze can still be reversed at mid-age by starvation. Genetically induced dietary restriction (eat-2) and genetic alterations that extend lifespan (eat-2, daf-2) have an impact on nematodes' maze performance. Lastly, we share preliminary results of a computer vision-based, custom- made tracking algorithm, especially developed for use in the challenging, 3-dimensional maze environment. This is the first time that learning in a structured maze environment is methodically portrayed and extensively characterized in C. elegans nematodes.