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[
International Worm Meeting,
2017]
Behavioural responses in C. elegans can be observed through changes in locomotive patterns. It is therefore important to consider the role of the physics in computational models of the neural circuit for motor behaviours. We present a dynamical systems model of C. elegans forward locomotion in which the neural circuit is divided into a series of repeating identical units, coupled via posterior stretch receptor feedback. Each unit includes cholinergic, bistable B-type motor neurons (modelled after bistable RMD neurons, Mellem et al. 2008, Boyle et al. 2012), implicit GABAergic D-type motor neurons (Boyle et al. 2012) and nonlinear viscoelastic muscle forcing along the body (Boyle et. al. 2012). The neural model incorporates proprioceptive feedback as the mechanism for producing sustained oscillations. Integrating the neural model with a recent continuum mechanical body model (Cohen and Ranner 2017) provides this feedback and is also the method for incorporating environmental drag from the surrounding fluid, closing the neuronal-environmental loop. Biophysically realistic parameters are used to obtain sustained travelling waves in muscle activation which respond to changes in environmental viscoelasticity. To explore the pattern generation mechanism, we present results from bifurcation analysis performed in the isolated neural framework and in the fully integrated neuro-mechanical model. We show how these results are modulated by changes in the external drag and internal material properties of the passive and active body. References [1] Boyle JH, Berri S, Cohen N: Gait modulation in c. elegans: an integrated neuro-mechanical model. Frontiers in computational neuroscience 2012, 6:10. [2] Mellem JE, Brockie PJ, Madsen DM, Maricq AV: Action potentials contribute to neuronal signaling in C. elegans, Nature Neuroscience 2008, 11:865-867 [3] Cohen N, Ranner T: A new computational method for a model of C. elegans biomechanics: Insights into elasticity and locomotion performance, arXiv:1702.04988, 20
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[
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
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[
International Worm Meeting,
2017]
Artificial light at night (ALAN) has many broad-scale and global implications for ecosystems and wildlife that have evolved under a 24-h circadian cycle. With increased urbanization, artificial light at night has directly altered natural photoperiods and nocturnal light intensity. Artificial light at night can disrupt behavioral patterns such as foraging activity and mating in animals. Disturbances in natural light and dark cycles also affect melatonin-regulated circadian and seasonal rhythms in Drosophila. We investigated the impact of ecologically relevant levels of light pollution on an important invertebrate model, Caenorhabditis elegans, as the impact of night lighting at these light levels is currently unknown. In this study, we exposed worms to artificial light at four intensities: 10-4 lx (control, comparable to natural nocturnal darkness), 10-2 lx (comparable to full-moon lighting and a low level of light pollution), 1 lx (comparable to dawn/dusk or intense light pollution), and 100 lx (dim daylight level comparable to extreme light pollution) on a 12L:12D photoperiod (100 lx treatments experienced constant light). We measured the impact of these light treatments on offspring production in hermaphroditic C. elegans. We grew worms for 2 generations in each light treatment, and then recorded the lifespan and counted the number of hatched offspring produced in the F3 generation. Our data show no significant differences among light levels for lifespan or offspring production suggesting that at least for these life history traits, ALAN does not affect these soil nematodes. Future directions include measuring additional life history traits and circadian gene expression for worms exposed to ALAN.
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[
International Worm Meeting,
2011]
A neuromechanical model of locomotion in C. elegans was recently proposed by Jordan H. Boyle [1]. One of the main results is that both swimming and crawling can be generated by a single neural circuit, reflexively modulated by the environment. This supports the known experimental results showing that different forms of C. elegans forward locomotion (e.g., swimming and crawling) can be described by a modulation of a single biomechanical gait [2]. The modelling result illustrates the importance and the potential of neuromechanical simulations for the analysis of the worm's behaviour.
In order to continue this work, and to make it usable by a broader audience, we have developed a similar neuromechanical model of the worm using CLONES. CLONES (Closed Loop Neural Simulation) is an open source framework for neuromechanical simulations. CLONES implements a communication interface between a neural simulator, called BRIAN [3], and a physics engine for biomedical applications, called SOFA [4]. BRIAN and SOFA are open-source simulators that are easy to use and provide high performance.
Our implementation of the worm's locomotion reproduces the neural model described in [1]. However, there are two key differences between the original physical model and our implementation. Firstly, Boyle's model considers that the body of the worm has zero mass (a low Reynolds number approximation). In contrast, the SOFA simulator allows us to integrate equations with mass and inertia. Secondly, the original model uses rigid rods of fixed length orthogonal to the body axis (approximating the incompressibility of the body due to high internal pressure). In SOFA rigid rods are modeled as springs of very high stiffness.
The physical system simulated in SOFA is described using a XML syntax. The neural network model interpreted by BRIAN is written in Python, using MATLAB-like syntax. Thus, the model is completely interpreted, and it is possible to visualize/interact with the simulation during runtime. Physical environments containing obstacles or chemical concentration gradients can be defined easily.
References
1. Boyle JH: C. elegans locomotion: an integrated approach. PhD thesis, university of Leeds, 2009
2. Berri S, Boyle JH, Tassieri M, Hope IA and Cohen N, Forward locomotion of the nematode C. elegans is achieved through modulation of a single gait HFSP J 3:186, 2009;
3. Goodman DF, Brette R: Brian: a simulator for spiking neural networks in Python. Front Neuroinform 2:5, 2008
4. Allard J, Cotin S, Faure F, Bensoussan PJ, Poyer F, Duriez C, Delingette H, Grisoni L: SOFA - an Open Source Framework for Medical Simulation. Medicine Meets Virtual Reality (MMVR'15), pp. 13-18, 2007.
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Xu, Rita, Boyle, Alan, Xiang, Yang K, Shen, Kang, Matus, David Q, Yee, Callista, Medwig-Kinney, Taylor N
[
International Worm Meeting,
2021]
Synapses are assembled during neuronal development and consist of a pre- and postsynapse, which are built from hundreds of proteins. While the molecular composition and architecture of pre- and postsynapses has been widely explored, much less is known about how synaptogenesis is regulated at the level of gene expression. Is there a mechanism that coordinates the expression of functionally related proteins such that they are ready to assemble into higher order structures concomitantly? In order to identify new players in presynaptic gene expression, our lab has conducted genetic screens and identified mutations that affect two subunits of the THO Complex (THOC), an RNA-binding complex implicated in mRNA export (Maeder et al., 2018). We have previously shown that in dopaminergic neurons, THOC is the primary machinery used for the export of synaptic transcripts. Mutation of THOC results in retention of these synaptic transcripts in the nucleus, while non-synaptic transcripts are largely unaffected and are exported normally. To date, it remains unclear how THOC is able to select such a specific set of targets for RNA export. Are there proteins that interact with THOC to instruct this behavior? Mass spectrometry studies conducted in mammalian systems revealed a novel interaction between EVI1/egl-43 and THOC (Ivanchoko et al., 2019). EGL-43 possesses 6 zinc fingers, all of which are highly homologous to the zinc fingers of EVI1. We performed ATAC-seq on sorted worm neuronal nuclei and identified putative regulatory regions of synaptic genes. Interestingly, we found that many of these regions contained the consensus DNA sequence that is recognized by EVI1. Using CRISPR/Cas9, we have tested the requirement of some of these binding sites and find that they are required for normal presynaptic gene expression. Depletion of EGL-43 through RNAi or auxin-mediated degredation similarly resulted in loss of synaptic markers in PDE. Using single molecule pulldown, we were able to detect weak but significant binding between EGL-43 and THOC. Taken together, our data suggests that EGL-43 could potentially be a link between THOC and its synaptic targets. References: Maeder et al., 2018, Cell 174, 1436-1449 Ivanchoko et al., 2019, Nucleic Acids Research 47, 1225-1238
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[
Worm Breeder's Gazette,
1989]
The map is now widely distributed electronically (see WBG 10(3), 67), but we are once again providing a summary for the gazette in the form of an output from the routine CHPLT. Do note that this is a provisional best guess, and that some linkages may later go away: please enquire if you need to know about the status of particular areas. When you receive cosmid clones, as stabs, please IMMEDIATELY streak them out on selective medium, pick small colonies, and grow 4ml minipreps (protocol from Alan Coulson if needed). For some cosmids, larger preps are liable to yield deleted DNA. Check that cosmid DNA appears full size (runs slower than lambda on agarose gels), then freeze a sample of good cells in 20% glycerol at -70 C. MRC computer account 'ARC' does not exist; Alan and John share account JES. A database node is now open at Seattle: modem number 206-467-2957; operator Phil Meneely. The summary of clone types given on the next page may be helpful when you are deciding which clones to request for your research. To reveal the most suitable clones for microinjection, the buried clones need to be displayed by the routine CONTASS; we will help you to do this if you ask. [See Figures 1- 3]
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[
Parasitol Today,
1996]
Parasitic nematode infections remain a major public health problem in many parts of the world. Because most of the current strategies aimed at controlling parasitic nematode infections have met with only limited success, it may be time to consider alternative approaches. An aspect of nematode biology that has drawn little attention as a target for control is the reproductive process. Although there are numerous facets of the overall reproductive biology of nematodes that hold potential as targets for intervention, Alan Scott here focuses on the male reproductive system, and outlines some of the known unique processes and characteristics of sperm formation and sperm function that could be exploited to block fertilization.
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[
Worm Breeder's Gazette,
1995]
The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK. We present here another progress report for the C. elegans genome sequencing project. The majority of chromosome I*II is now essentially complete, although some gaps remain where cosmids were not available (Figure 1). While we are rescuing these regions from YACs and lambda clones, we will continue to sequence the cosmid-rich regions of other chromosomes. In the previous issue of the WBG, we reported significant protein similarities (blastx score >100) for several cosmids in the central region of chromosome II. Since then, we have made considerable progress on much of the remainder of this region. Protein similarities for several additional cosmids from chromosome II are presented in Table 1 (all cosmids for which shotgun sequencing has been completed). We also have begun sequencing cosmids near the center of the X chromosome. The St. Louis group started with cosmid C23F12 (near
kin-11) and are moving right to left along the physical map. The Sanger Centre group are moving left to right from the same starting point. Similarity data for X chromosome cosmids which have been processed through the initial shotgun phase are also included in Table 1. For each putative genomic locus, the highest blastx score and a brief identifier are listed. Although the cosmids which contain database hits may not be completely sequenced, the Consortium will make preliminary sequence data available to the community with the caveat that it is preliminary and may still contain errors. Finished cosmid sequences are now available by anonymous ftp at: ftp.sanger.ac.uk (directory: pub/C.elegans_sequences). For further information on blastx similarities, please contact LaDeana Hillier (lhillier@watson.wustl.edu) or Steve Jones (sjj@sanger.ac.uk). For information on sequencing plans or estimated completion times, please contact Richard Wilson (rwilson@watson.wustl.edu) or Alan Coulson (alan@sanger.ac.uk). All requests for cosmid clones should be addressed to Alan Coulson. For further information about the C. elegans genome project including our policy statement about sharing both data and sequencing expertise, please contact Richard Wilson.
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[
Worm Breeder's Gazette,
1984]
I have examined a total of eight independent
lin-12 null mutations that arose spontaneously in a predominantly Bergerac genetic background. I probed genomic Southern blots with a 1.2 kb wild-type HindIII fragment that was defined by an insertion mutation (see last Newsletter) and/or with a cosmid 'contig' obtained from Alan Coulson and John Sulston that extends approximately 20 kb in each direction from the 1.2 kb HindIII fragment. The results thus far indicate that ( 1) seven of the eight mutations are associated with Tc1 insertions (2) the insertions are at different sites, and (3) all the insertion sites may lie within a single Pst fragment that is 2.8 kb in wild-type.
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[
Nature,
1998]
In 1983, John Sulston and Alan Coulson began to construct a complete physical map of the genome of the nematode worm Caenorhabditis elegans, and started what became known as the C. elegans Genome Project. At the time, several people wondered why John, who had just described all of the cell divisions in C. elegans (the cell lineage), was interested in this project rather than in a more 'biological' problem. He replied by joking that he had a "weakness for grandiose, meaningless projects". In 1989, as the physical map approached completion, the Genome Project, now including Bob Waterston and his group, embarked on the even more ambitious goal of obtaining the complete genomic sequence