Wu GY et al. (1998) Proc Natl Acad Sci U S A "Evidence for functional and physical association between Caenorhabditis elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin."

Kitajewski JK, Wu GY, Greenwald IS, Hubbard EJA

[Proc Natl Acad Sci U S A, 1998]

Mutations in either of two human presenilin genes (PS1 and PS2) cause Alzheimer's disease. Here we describe genetic and physical interactions between Caenorhabditis elegans SEL-10, a member of the Cdc4p family of proteins, and SEL-12, a C. elegans presenilin. We show that loss of sel-10 activity can suppress the egg-laying defective phenotype associated with reducing sel-12 activity, and that SEL-10 can physically complex with SEL-12. Proteins of the Cdc4p family have been shown to target proteins for ubiquitin-mediated turnover. The functional and physical interaction between sel-10 and sel-12 therefore offers an approach to understanding how presenilin levels are normally regulated.

Cucinotta FA et al. (1994) Radiat Prot Dosimetry "Radiosensitivity parameters for lethal mutagenesis in Caenorhabditis elegans."

Katz R, Cucinotta FA, Wilson JW

[Radiat Prot Dosimetry, 1994]

For the first time track structure theory has been applied to radiobiological effects in a living organism. Data for lethal mutagenesis in Caenorhabditis elegans, obtained after irradiation with nine different types of ions of atomic number 1-57 and gamma rays have yielded radiosensitivity parameters (E0, sigma 0, kappa, m = 68 Gy, 2.5 x 10(-9) cm2, 750, 2) comparable with those found for the transformation of C3HT10 1/2 cells (180 Gy, 1.15 x 10(-10) cm2, 750, 2) but remote from those (E0 and sigma 0 = approximately 2 Gy, approximately 5 x 10(-7) cm2) for mammalian cell survival.

Yu W et al. Dose Response "Study on Caenorhabditis Elegans as a Combined Model of Microdosimetry and Biology."

Gao J, Sun L, Long H, Chen N, Yu W, Tu Y, Wang Y

[Dose Response]

Microdosimetry is a tool for the investigation of microscopic energy deposition of ionizing radiation. This work used <i>Caenorhabditis</i> elegans as a model to estimate the microdosimetric deposition level at the ⁶⁰Co gamma radiation. Monte Carlo software PHITS was employed to establish irradiated nematodes model. The dose deposition of the entire body and gonad irradiated to 100 Gy was calculated. The injury levels of radiation were evaluated by the detection of biological indicators. The result of microdosimetric experiment suggested that the dose of whole body of nematodes was estimated to be 99.9 +/- 57.8 Gy, ranging from 19.6 to 332.2 Gy. The dose of gonad was predicted to be 129.4 +/- 558.8 Gy (9.5-6597 Gy). The result of biological experiment suggested that there were little changes in the length of nematodes after irradiation. However, times of head thrash per minute and the spawning yield in 3 consecutive days decreased 27.1% and 94.7%, respectively. Nematodes in the irradiated group displayed heterogeneity. Through contour analysis, trends of behavior kinematics and reproductive capacity of irradiated nematodes proved to be consistent with the dose distribution levels estimated by microdosimetric model. Finally, <i>C</i>. elegans presented a suitable combined model of microdosimetry and biology for studying radiation.

Cannon, Kelli et al. (2021) International Worm Meeting "LITE-1 mediates behavioral responses to X-rays in C. elegans"

Anker, Jeff, Dobrunz, Lynn, Ranasinghe, Meena, Cannon, Kelli, Bolding, Mark

[International Worm Meeting, 2021]

While prompt sensory detection of X-rays has been documented across a wide variety of species, relatively few studies have explored the underlying molecular mechanisms of these acute sensory responses. Here we report the discovery of an acute behavioral avoidance response in wild type C. elegans to X-ray stimulation. The endogenous C. elegans photoreceptor protein LITE-1, which mediates UV-avoidance behavior, was found to also underlie a similar behavioral response to X-radiation. We observed that wild type nematodes exhibited a dramatic avoidance response to 1 Gy/s focused X-ray stimulation. The response consisted of a marked increase in activity, involving increased forward locomotion, omega bends, and reversals, observed within 2 s of stimulation onset and subsiding once the worm escaped the path of the focused X-ray beam. Moderate dose rates of 0.5 and 0.7 Gy/s evoked similar, but somewhat slower and less vigorous responses, while 0.2 Gy/s and sham (0 Gy/s) stimulation did not elicit any significant response. Nematodes with the lite-1(ce314) mutation, which renders LITE-1 dysfunctional, failed to exhibit the X-ray avoidance behavioral phenotype seen in wild type and lite-1 intact mutant strains, suggesting that functional lite-1 is critical for the X-ray avoidance response. To verify LITE-1's sensitivity to X-rays and determine whether ectopic expression of lite-1 can confer X-ray sensitivity to otherwise X-ray insensitive cells, we administered unfocused X-ray stimulation to swimming pmyo-3::lite-1 worms, which transgenically express lite-1 in myocytes. Transgenic, but not wild type, nematodes exhibited a strong paralysis response, quantified as a dramatic decrease in body bend frequency and sometimes accompanied by egg ejection, in response to the stimulation. High dose rates of 0.56 and 0.74 Gy/s produced the most extreme effects, however, paralysis responses were seen at X-ray intensities as low as 0.19 Gy/s. Together, these results suggest that LITE-1 can function as an X-ray sensitive receptor, playing a critical role in the transduction of X-ray signals into neural activity to produce behavioral responses. This is the first demonstration of X-ray based optogenetic (X-genetic) manipulation of cellular electrical activity in intact behaving animals. As such, LITE-1 shows strong potential for use in this novel method of neuromodulation to transduce transcranial X-ray signals for precise, but minimally invasive manipulation of neural activity in mammals.

Castillo-Quan JI et al. (2016) Cell "Metformin: Restraining Nucleocytoplasmic Shuttling to Fight Cancer and Aging."

Blackwell TK, Castillo-Quan JI

[Cell, 2016]

In this issue of Cell, Wu etal. employed C.elegans and human cell experiments to identify a pathway through which metformin increases lifespan and inhibits growth. A key transcriptional target, ACAD10, is activated when metformin induces nuclear exclusion of the GTPase RagC, thereby inhibiting mTORC1 through an unexpected mechanism.

Ji Wu et al. (2002) East Coast Worm Meeting "Regulation of Touch Cell Functional Genes"

Martin Chalfie, Ji Wu

[East Coast Worm Meeting, 2002]

We have previously shown that egl-44 and egl-46 are two transcription regulators involved in the development of several types of neurons in C. elegans, with significant homology in other organisms, and that they repress the expression of touch cell-specific features in FLP neurons (Wu et al., 2001,Genes. Dev., 15: 789).

Hubbard EJA et al. (1997) International C. elegans Meeting "SEL-10, A NEGATIVE REGULATOR OF LIN-12-MEDIATED SIGNALLING IN C.ELEGANS"

Kitajewski JK, Hubbard EJA, Wu GY, Greenwald IS

[International C. elegans Meeting, 1997]

Receptors of the LIN-12/Notch family are found throughout the animal kingdom and are activated by binding ligands of the Delta/Serrate/LAG-2 family. In order to understand the consequences of receptor activation that result in cell fate decisions, modifiers and regulators of the pathway must be identified and characterized. One way to influence the outcome of ligand-receptor interactions is to regulate the stability of the ligand, the receptor or downstream components of the pathway. We have identified and characterized sel-10, a potent modifier of the lin-12 pathway that appears to act at the level of protein turnover. Mutations in sel-10 were identified in a screen for suppressors of phenotypes associated with reduced lin-12 activity (Sundaram and Greenwald, 1993). Hypomorphic alleles of sel-10 suppress defects associated with reduced lin-12 activity and dramatically enhance defects associated with constitutively activated lin-12 alleles, including defects caused by expression of the lin-12 intracellular domain. In addition, sel-10 mutants display low penetrance phenotypes associated with increased lin-12 activity. Therefore, reduction of sel-10 elevates lin-12 activity, implicating sel-10(+) in negative regulation of lin-12 signalling. Using an anti-suppression assay, we cloned sel-10 and found that it encodes a member of the CDC4 subfamily of WD40 repeat containing proteins. In yeast, CDC4 is involved in targeting cell-cycle control proteins for degradation via ubiquitination. We have obtained preliminary biochemical evidence that SEL-10 can reduce the steady-state level of LIN-12/Notch proteins, and we are currently testing the hypothesis that SEL-10 influences lin-12-mediated signalling by reducing the steady-state level of the activated receptor.

Tetsuya Sakashita et al. (2005) International Worm Meeting "Effects of ionizing irradiation on chemo-attraction to NaCl and food-NaCl associative learning of C. elegans"

Tetsuya Sakashita, Daisuke D Ikeda, Yasuhiko Kobayashi, Seiichi Wada, Tomoo Funayama, Nobuyuki Hamada

[International Worm Meeting, 2005]

The nematode Caenorhabditis elegans is known as a model organism for functional analysis of a neuron network. It remains unclear how ionizing radiation affects a neuron network itself, although that the radiation-induced learning and memory impairments are caused by suppression of hippocampal neurogenesis is a theory is reported by many researchers. Of our particular interest is the neuron network response of C. elegans to ionizing irradiation and the present study therefore aims to investigate radiation-induced responses of chemo-attraction to NaCl and food-NaCl associative learning of C. elegans in the adult stage when neurogenesis does not occur. Caenorhabditis elegans wild type strain var. Bristol N2 was used for all experiments. The animals were irradiated with 60Co gamma rays (0, 100, 500 and 1000 Gy). Chemotaxis towards NaCl was not significantly inhibited by gamma rays irradiation (< 500 Gy). The result means that sensing, signaling and locomotion in chemo-attraction to NaCl are maintained under gamma rays irradiation less than 500 Gy. When animals at both cases of pre-conditioning and conditioning using food-/NaCl+ plates were irradiated with gamma rays (> 100 Gy), their chemotaxis was significantly decreased than that of non-irradiated ones. This indicates that the associative learning under the presence of NaCl and the absence of food is enhanced by gamma rays irradiation. Our findings suggest that the associative learning enhancement is induced in the adult animals of C. elegans by 60Co gamma rays irradiation at the dose range of no effects on chemo-attraction; in other words, not sensing but signaling (information processing) in the neuron network of C. elegans could be changed by 60Co gamma-rays irradiation.

Brissette B et al. (2019) Neuron "Insulin-like Peptides as Agents of Social Change."

Ringstad N, Brissette B

[Neuron, 2019]

Many behaviors promote reproduction or food finding. These critical functions of behavior can conflict; successful reproductive strategies can grow populations to the point where food is depleted. In this issue of Neuron, Wu etal. (2019) show how the nematode C.elegans detects crowding to change feeding behavior by coupling pheromone sensing to signaling via insulin-like peptides.

Maremonti E et al. Mutat Res "Ionizing radiation, genotoxic stress, and mitochondrial DNA copy-number variation in Caenorhabditis elegans: droplet digital PCR analysis."

Berg ES, Maremonti E, Brede DA, Eide DM, Olsen AK

[Mutat Res]

Mitochondria are vulnerable to the effects of ionizing radiation; damage to mitochondrial DNA (mtDNA) may be more extensive and persistent than damage to nuclear DNA (nDNA). Variation in mtDNA copy number has been proposed as a marker for mitochondrial dysfunction in response to ionizing radiation. We have developed a precise and sensitive duplex droplet digital PCR (ddPCR) method for quantitation of the mtDNA/nDNA ratio in the model organism Caenorhabditis elegans. The effect on this ratio was investigated over a wide range of doses (0.03-72 Gy) of chronic gamma irradiation. Five mitochondrial targets and two nuclear reference genes were amplified pairwise in duplex PCR format (one mitochondrial and one nuclear target per PCR) by both ddPCR and quantitative PCR (qPCR). The results showed that ddPCR but not qPCR enabled detection of a significant increase in mtDNA copy number (1.6 +/- 0.1-fold) for nematodes exposed to high doses (24 Gy). Thus, ddPCR provided higher precision and greater sensitivity than qPCR for detection of mtDNA copy number variation. The variation followed a Hill-type dose response with threshold 10.3 +/- 1 Gy. This strongly suggests that chronic genotoxic stress affects mtDNA replication. The duplex ddPCR method is a novel, high-precision, sensitive tool for determination of mitochondrial DNA copy number variation and function in C. elegans.