Hodgkin J (2017) Genetics "Frontiers of Knowledge: An Interview with 2017 Edward Novitski Prize Recipient Jonathan Hodgkin."

Hodgkin J

[Genetics, 2017]

The Genetics Society of America's Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity and intellectual ingenuity has been used to design and execute scientific experiments to solve a difficult problem in genetics. The 2017 winner, Jonathan Hodgkin, used elegant genetic studies to unravel the sex determination pathway in Caenorhabditis elegans He inferred the order of genes in the pathway and their modes of regulation using epistasis analyses-a powerful tool that was quickly adopted by other researchers. He expanded the number and use of informational suppressor mutants in C. elegans that are able to act on many genes. He also introduced the use of collections of wild C. elegans to study naturally occurring genetic variation, paving the way for SNP mapping and QTL analysis, as well as studies of hybrid incompatibilities between worm species. His current work focuses on nematode-bacterial interactions and innate immunity.

Kunitomo, Hirofumi et al. (2020) MicroPubl Biol

Iino, Yuichi, Kunitomo, Hirofumi

[MicroPubl Biol, 2020]

Mechanisms of chemotactic behaviors have been of great interest in C. elegans neuroscience since the early days of its research (Ward 1973). Lewis and Hodgkin (1977) systematically isolated more than ten abnormal chemotaxis (che) mutants that showed defective chemotaxis to sodium (Na+) and chloride (Cl-) ions (Lewis and Hodgkin 1977), whose responsible genes have already been molecularly characterized except for che-5(e1073). We here show that che-5(e1073) is a missense allele of gcy-22, which encodes a receptor guanylyl cyclase (rGC) specifically expressed in the ASE-right (ASER) gustatory neuron and is essential for chemosensation through the neuron.

Ahmed S et al. (2000) Nature "MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans."

Hodgkin JA, Ahmed S

[Nature, 2000]

The germ line is an immortal cell lineage that is passed indefinitely from one generation to the next. To identify the genes that are required for germline immortality, we isolated Caenorhabditis elegans mutants with mortal germ lines--worms that can reproduce for several healthy generations but eventually become sterile. One of these mortal germline (mrt) mutants, mrt-2, exhibits progressive telomere shortening and accumulates end-to-end chromosome fusions in later generations, indicating that the MRT-2 protein is required for telomere replication. In addition, the germ line of mrt-2 is hypersensitive to X-rays and to transposon activity. Therefore, mrt-2 has defects in responding both to damaged DNA and to normal double-strand breaks present at telomeres. mrt-2 encodes a homologue of a checkpoint gene that is required to sense DNA damage in yeast. These results indicate that telomeres may be identified as a type of DNA damage and then repaired by the telomere-replication enzyme telomerase.AD - MRC Laboratory of Molecular Biology, Cambridge, UK. shawn@mrc-lmb.cam.ac.ukFAU - Ahmed, SAU - Ahmed SFAU - Hodgkin, JAU - Hodgkin JLA - engSI - GENBANK/AF073524SI - GENBANK/AF074718SI - GENBANK/AF076843SI - GENBANK/AF124501SI - GENBANK/P14746SI - GENBANK/P22193SI - GENBANK/P48581PT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (DNA, Helminth)RN - 0 (Helminth Proteins)RN - 0 (MRT-2 protein)SB - IM

Li S et al. (2022) Front Neurosci "Energy efficiency and coding of neural network."

Yan C, Liu Y, Li S

[Front Neurosci, 2022]

Based on the Hodgkin-Huxley model, this study explored the energy efficiency of BA network, ER network, WS network, and Caenorhabditis elegans neural network, and explained the development of neural network structure in the brain from the perspective of energy efficiency using energy coding theory. The numerical simulation results showed that the BA network had higher energy efficiency, which was closer to that of the C. elegans neural network, indicating that the neural network in the brain had scale-free property because of satisfying high energy efficiency. In addition, the relationship between the energy consumption of neural networks and synchronization was established by applying energy coding. The stronger the neural network synchronization was, the less energy the network consumed.

Lopez-Puebla, Araceli et al. (2019) MicroPubl Biol

Lopez-Puebla, Araceli, Gomez-Cepeda, Kitzia, Mayoral-Penya, Zyanya, Arellano-Carbajal, Fausto

[MicroPubl Biol, 2019]

Burrowing was originally described for C. elegans as worms that tended to stay below the surface of the agar when maintaining high densities of nematodes on agar (Hodgkin and Doniach, 1997). The neuropeptide receptor NPR-1 regulates food-related behaviors (de Bono and Bargmann, 1998). The canonical TGF- signaling pathway responds to environmental signals by regulating egg laying and feeding (Gumienny and Savage-Dunn, 2013). The TGF- like ligand DAF-7 functions as a sensor of environmental conditions (Greer et al., 2008). As the aggregating mutant strain npr-1 appeared to burrow more than the wild-type N2 strain (Hodgkin and Doniach, 1997; de Bono and Bargmann, 1998), it was suggested that aggregation preludes burrowing (Rogers et al., 2006). Considering that daf-7 mutants also aggregate on food (Thomas et al., 1993; de Bono et al., 2002), we examined whether daf-7 mutants also exhibit burrowing behavior.   The burrowing assay consisted in using 3.5-cm NGM plates with eight concentric perforations made at 0.875 cm from the edge of the plate. Perforations were made by puncturing the agar with a sterile 0.5 l pipette tip until reaching the bottom surface of the dish. 10 nematodes were transferred to the plates after perforations had been made. The number of worms within the agar was counted after 2 h. Fifty experimental replicates for wild-type strain N2 and mutant strains daf-7 and npr-1 were done per assay. This number of replicates yielded a statistical power 0.85. All agar plates were prepared two days prior to the assays to ensure stability and reduce excessive moisture (Brenner, 1974). We discarded any plate that showed fractures in the agars surface. In order to compare burrowing between wild-type worms and each of the mutant strains we used Chi-square tests. We also calculated the odds ratio (OR) and 95% confidence intervals. Analysis were run in R 3.3.1 (R Core Team, 2015). Fisher exact p-values and odds ratios were calculated with R package Epitools.   Mutant strains npr-1 and daf-7 behaved similarly on the agar plates with perforations, where they were more likely to burrow than the wild-type strain (npr-1 vs. N2: Chi2=4.79, p=0.03; OR=1.63, 95% CI=1.04-2.52; daf-7 vs. N2: Chi2=5.23, p=0.02; OR=1.66, 95% CI=1.07-2.57) (Figure 1). Past studies have reported that the aggregating strain npr-1 burrows more than the N2 strain (Hodgkin and Doniach, 1997; de Bono and Bargmann, 1998). We found that both aggregating strains npr-1 and daf-7 tended to exhibit similar burrowing behavior on agar plates when perforations were present. A study that focused on foraging proposed that burrowing was likely to occur as a way to avoid hyperoxia at the surface of the agar plate (Rogers et al., 2006). Considering that daf-7 mutants avoid hyperoxia (Chang et al., 2006), the burrowing behavior observed in daf-7 mutants might be further evidence that this behavior is induced in response to hyperoxia, as is known to explain aggregation behavior. We have tested only a single mutant allele for daf-7, therefore these data are preliminary. In addition, further testing of other genes acting in the TGF- signaling pathway, for which there exist reports that their mutants exhibit aggregation behavior, such as daf-1, daf-8 and daf-14 (Thomas et al., 1993), would support our findings that TGF- pathway regulates burrowing behavior.

Nickell WT et al. (2002) J Membr Biol "Single ionic channels of two Caenorhabditis elegans chemosensory neurons in native membrane."

Pun RYK, Nickell WT, Bargmann CI, Pun RY, Kleene SJ

[J Membr Biol, 2002]

The genome of Caenorhabditis elegrans contains representatives of the channel families found in both vertebrate and invertebrate nervous systems. However, it lacks the ubiquitous Hodgkin-Huxley Na+ channel that is integral to long-distance signaling in other animals. Nematode neurons are presumed to communicate by electrotonic conduction and graded depolarizations. This fundamental difference in operating principle may require different channel populations to regulate transmission and transmitter release. We have sampled ionic channels from the somata of two chemosensory neurons (AWA and AWC) of C. elegans. A Ca2+-activated, outwardly rectifying channel has a conductance of 67 pS and a reversal potential indicating selectivity for K+. An inwardly rectifying channel is active at potentials more negative than -50 mV. The inward channel is notably flickery even in the absence of divalent cations; this prevented determination of its conductance and reversal potential. Both of these channels were inactive over a range of membrane potentials near the likely cell resting potential; this would account for the region of very high membrane resistance observed in whole-cell recordings. A very-large-conductance (>100 pS), inwardly rectifying channel may account for channel-like fluctuations seen in whole-cell recordings.

Sleeman BD et al. (2024) Math Biosci "A theoretical model of anaphase."

Stewart IW, Sleeman BD

[Math Biosci, 2024]

This paper develops a theory for anaphase in cells. After a brief description of microtubules, the mitotic spindle and the centrosome, a mathematical model for anaphase is introduced and developed in the context of the cell cytoplasm and liquid crystalline structures. Prophase, prometaphase and metaphase are then briefly described in order to focus on anaphase, which is the main study of this paper. The entities involved are modelled in terms of liquid crystal defects and microtubules are represented as defect flux lines. The mathematical techniques employed make extensive use of energy considerations based on the work that was developed by Dafermos (1970) from the classical Frank-Oseen nematic liquid crystal energy (Frank, 1958; Oseen, 1933). With regard to liquid crystal theory we introduce the concept of regions of influence for defects which it is believed have important implications beyond the subject of this paper. The results of this paper align with observed biochemical phenomena and are explored in application to HeLa cells and Caenorhabditis elegans. This unified approach offers the possibility of gaining insight into various consequences of mitotic abnormalities which may result in Down syndrome, Hodgkin lymphoma, breast, prostate and various other types of cancer.

Wood WB et al. (1985) Cold Spring Harb Symp Quant Biol "Aspects of dosage compensation and sex determination in Caenorhabditis elegans."

Schedin P, Wood WB, Donahue LM, Meneely PM

[Cold Spring Harb Symp Quant Biol, 1985]

The nematode Caenorhabditis elegans has two sexes, hermaphrodites and males. Hermaphrodites normally have two X chromosomes (XX or 2X) and males only one (XO or 1X). There is no Y chromosome, and sex is determined by the X/A ratio, i.e., the ratio of X chromosomes to sets of autosomes. The X/A ratio acts to determine sex through a set of at least seven interacting autosomal genes, which have been defined, characterized, and shown to act as a regulatory pathway, primarily by Hodgkin and co-workers. The first gene in the pathway, her-1, acts through five intervening genes to regulate the major switch gene tra-1, whose activity determines somatic sexual development. At an X/A ratio of 1.0, her-1 activity is low and tra-1 acivity is high, leading to hermaphrodite development. At an X/A ratio of 0.5, her-1 activity is high and tra-1 activity is low, leading to male development. Loss-of-function mutations in the her-1 gene transform 1X animals into fertile hermaphrodites and have no effect on 2X hermaphrodites. Loss-of-function mutations in the tra-1 gene transform 2X animals into fertile males and have no effect on 1X males....

Li L et al. (1998) Mol Cell Biol "Differential expression of individual suppressor tRNA(Trp) gene gene family members in vitro and in vivo in the nematode Caenorhabditis elegans."

Kondo K, Li L, Honda BM, Linning RM

[Mol Cell Biol, 1998]

Eight different amber suppressor tRNA (suptRNA) mutations in the nematode Caenorhabditis elegans have been isolated; all are derived from members of the tRNA(Trp) gene family (K. Kondo, B. Makovec, R. H. Waterston, and J. Hodgkin, J. Mol. Biol. 215:7-19, 1990). Genetic assays of suppressor activity suggested that individual tRNA genes were differentially expressed, probably in a tissue- or developmental stage-specific manner. We have now examined the expression of representative members of this gene family both in vitro, using transcription in embryonic cell extracts, and in vivo, by assaying suppression of an amber-mutated lacZ reporter gene in animals carrying different suptRNA mutations. Individual wild-type tRNA(Trp) genes and their amber-suppressing counterparts appear to be transcribed and processed identically in vitro, suggesting that the behavior of suptRNAs should reflect wild-type tRNA expression. The levels of transcription of different suptRNA genes closely parallel the extent of genetic suppression in vivo. The results suggest that differential expression of tRNA genes is most likely at the transcriptional rather than the posttranscriptional level and that 5' flanking sequences play a role in vitro, and probably in vivo as well. Using suppression of a lacZ(Am) reporter gene as a more direct assay of suptRNA activity in individual cell types, we have again observed differential expression which correlates with genetic and in vitro transcription results. This provides a model system to more extensively study the basis for differential expression of this tRNA gene family.

Pierce JT (2018) J Gen Physiol "Calnexin revealed as an ether-a-go-go chaperone by getting mutant worms up and going."

Pierce JT

[J Gen Physiol, 2018]

The role of ion channels in cell excitability was first revealed in a series of voltage clamp experiments by Hodgkin and Huxley in the 1950s. However, it was not until the 1970s that patch-clamp recording ushered in a revolution that allowed physiologists to witness how ion channels flicker open and closed at angstrom scale and with microsecond resolution. The unexpectedly tight seal made by the patch pipette in the whole-cell configuration later allowed molecular biologists to suck up the insides of identified cells to unveil their unique molecular contents. By refining these techniques, researchers have scrutinized the surface and contents of excitable cells in detail over the past few decades. However, these powerful approaches do not discern which molecules are responsible for the dynamic control of the genesis, abundance, and subcellular localization of ion channels. In this dark territory, teams of unknown and poorly understood molecules guide specific ion channels through translation, folding, and modification, and then they shuttle them toward and away from distinct membrane domains via different subcellular routes. A central challenge in understanding these processes is the likelihood that these diverse regulatory molecules may be specific to ion channel subtypes, cell types, and circumstance. In work described in this issue, Bai et al. (2018. <i>J. Gen. Physiol.</i> https://doi.org/10.1085/jgp.201812025) begin to shed light on the biogenesis of UNC-103, a K⁺ channel found in <i>Caenorhabditis elegans</i>.