OpenWorm

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OpenWorm is an international open science project for the purpose of simulating the roundworm Caenorhabditis elegans at the cellular level. [1] [2] [3] Although the long-term goal is to model all 959 cells of the C. elegans, the first stage is to model the worm's locomotion by simulating the 302 neurons and 95 muscle cells. This bottom up simulation is being pursued by the OpenWorm community.

Contents

As of 2014, a physics engine called Sibernetic has been built for the project and models of the neural connectome and a muscle cell have been created in NeuroML format. A 3D model of the worm anatomy can be accessed through the web via the OpenWorm browser. The OpenWorm project is also contributing to develop Geppetto, [4] a web-based multi-algorithm, multi-scale simulation platform engineered to support the simulation of the whole organism. [5]

Background: C. elegans

The roundworm Caenorhabditis elegans is a free-living, transparent nematode, about 1 mm in length, [6] that lives in temperate soil environments. It is the type species of its genus. [7]

An adult Caenorhabditis elegans worm Adult Caenorhabditis elegans.jpg
An adult Caenorhabditis elegans worm

C. elegans has one of the simplest nervous systems of any organism—its hermaphrodite type possesses only 302 neurons. Furthermore, the structural connectome of these neurons is fully worked out. There are fewer than one thousand cells in the whole body of a C. elegans worm, and because C. elegans is a model organism, each has a unique identifier and comprehensive supporting literature. Being a model organism, the genome is fully known, along with many well characterized mutants readily available, and a comprehensive literature of behavioural studies. With so few neurons and new 2-photon calcium microscopy techniques, it should soon be possible to record the complete neural activity of a living organism. The manipulation of neurons via optogenetic methods, in tandem with the foregoing technical capacities, has provided the project an unprecedented position—now able to fully characterize the neural dynamics of an entire organism.

The efforts to build an in silico model of C. elegans, although a relatively simple organism, have burgeoned the development of technologies that will make it easier to model progressively more complex organisms.

OpenWorm project

While the ultimate goal is to simulate all features of C. elegans' behaviour, the OpenWorm community initially aimed to simulate a simple motor response: teaching the worm to crawl. To do so, the virtual worm is placed in a virtual environment. A full feedback loop is subsequently established: Environmental Stimulus > Sensory Transduction > Interneuron Firing > Motor Neuron Firing > Motor Output > Environmental Change > Sensory Transduction.

There are two main technical challenges here: modelling the neural/electrical properties of the brain as it processes the information, and modelling the mechanical properties of the body as it moves. The neural properties are being modeled by a Hodgkin-Huxley model, and the mechanical properties are being modeled by a Smoothed Particle Hydrodynamics algorithm.

The OpenWorm team built an engine called Geppetto which could integrate these algorithms and due to its modularity will be able to model other biological systems (like digestion) which the team will tackle at a later time.

The team also built an environment called NeuroConstruct which is able to output neural structures in NeuroML. Using NeuroConstruct the team reconstructed the full connectome of C. elegans.

Using NeuroML the team has also built a model of a muscle cell. Note that these models currently only model the relevant properties for the simple motor response: the neural/electrical and the mechanical properties discussed above.

The next step is to connect this muscle cell to the six neurons which synapse on it and approximate their effect.

The rough plan is to then both:

Progress

As of January 2015, the project is still awaiting peer review, and researchers involved in the project are reluctant to make bold claims about its current resemblance to biological behavior; project coordinator Stephen Larson estimates that they are "only 20 to 30 percent of the way towards where we need to get". [8]

As of 2021, a whole brain emulation has not yet been achieved. [9]

In 1998 Japanese researchers announced the Perfect C. elegans Project. A proposal was submitted, but the project appears to have been abandoned. [10] [11]

In 2004 a group from Hiroshima began the Virtual C. elegans Project. They released two papers which showed how their simulation would retract from virtual prodding. [12] [13]

In 2005 a Texas researcher described a simplified C. elegans simulator based on a 1-wire network incorporating a digital Parallax Basic Stamp processor, sensory inputs and motor outputs. Inputs employed 16-bit A/D converters attached to operational amplifier simulated neurons and a 1-wire temperature sensor. Motor outputs were controlled by 256-position digital potentiometers and 8-bit digital ports. Artificial muscle action was based on Nitinol actuators. It used a "sense-process-react" operating loop which recreated several instinctual behaviors. [14]

These early attempts of simulation have been criticized for not being biologically realistic. Although we have the complete structural connectome, we do not know the synaptic weights at each of the known synapses. We do not even know whether the synapses are inhibitory or excitatory. To compensate for this the Hiroshima group used machine learning to find some weights of the synapses which would generate the desired behaviour. It is therefore no surprise that the model displayed the behaviour, and it may not represent true understanding of the system.

Open science

The OpenWorm community is committed to the ideals of open science. Generally this means that the team will try to publish in open access journals and include all data gathered (to avoid the file drawer problem). Indeed, all the biological data the team has gathered is publicly available, and the five publications the group has made so far are available for free on their website. All the software that OpenWorm has produced is completely free and open source.

OpenWorm is also trying a radically open model of scientific collaboration. The team consists of anyone who wishes to be a part of it. There are over one hundred "members" who are signed up for the high volume technical mailing list. Of the most active members who are named on a publication there are collaborators from Russia, Brazil, England, Scotland, Ireland and the United States. To coordinate this international effort, the team uses "virtual lab meetings" and other online tools that are detailed in the resources section.

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The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. The brain is the largest cluster of neurons in the body and is typically located in the head, usually near organs for special senses such as vision, hearing and olfaction. It is the most specialized and energy-consuming organ in the body, responsible for complex sensory perception, motor control, endocrine regulation and the development of intelligence.

<span class="mw-page-title-main">Nervous system</span> Part of an animal that coordinates actions and senses

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<i>Caenorhabditis elegans</i> Free-living species of nematode

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Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems. Their neuroanatomy is therefore better understood. In vertebrates, the nervous system is segregated into the internal structure of the brain and spinal cord and the series of nerves that connect the CNS to the rest of the body. Breaking down and identifying specific parts of the nervous system has been crucial for figuring out how it operates. For example, much of what neuroscientists have learned comes from observing how damage or "lesions" to specific brain areas affects behavior or other neural functions.

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<span class="mw-page-title-main">Connectome</span> Comprehensive map of neural connections in the brain

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<span class="mw-page-title-main">William Schafer</span> American geneticist

William Ronald Schafer is a neuroscientist and geneticist who has made important contributions to understanding the molecular and neural basis of behaviour. His work, principally in the nematode C. elegans, has used an interdisciplinary approach to investigate how small groups of neurons generate behavior, and he has pioneered methodological approaches, including optogenetic neuroimaging and automated behavioural phenotyping, that have been widely influential in the broader neuroscience field. He has made significant discoveries on the functional properties of ionotropic receptors in sensory transduction and on the roles of gap junctions and extrasynaptic modulation in neuronal microcircuits. More recently, he has applied theoretical ideas from network science and control theory to investigate the structure and function of simple neuronal connectomes, with the goal of understanding conserved computational principles in larger brains. He is an EMBO member, Welcome Investigator and Fellow of the Academy of Medical Sciences.

Eileen Southgate is a British biologist who mapped the complete nervous system of the roundworm Caenorhabditis elegans, together with John White, Nichol Thomson, and Sydney Brenner. The work, done largely by hand-tracing thousands of serial section electron micrographs, was the first complete nervous system map of any animal and it helped establish C. elegans as a model organism. Among other projects carried out as a laboratory assistant at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB), Southgate contributed to work on solving the structure of hemoglobin with Max Perutz and John Kendrew, and investigating the causes of sickle cell disease with Vernon Ingram.

References

  1. Chirgwin, Richard (5 May 2014). "What's that PARASITE wriggling inside my browser? Nematode fanciers open their worm to a Kickstarter". The Register.
  2. Palyanov, Andrey; Khayrulin, Sergey; Larson, Stephen D.; Dibert, Alexander (2012-01-01). "Towards a virtual C. elegans: A framework for simulation and visualization of the neuromuscular system in a 3D physical environment". In Silico Biology. 11 (3): 137–147. doi:10.3233/isb-2012-0445. ISSN   1386-6338. PMID   22935967.
  3. Gewaltig, Marc-Oliver; Cannon, Robert (2014-01-23). "Current Practice in Software Development for Computational Neuroscience and How to Improve It". PLOS Computational Biology. 10 (1): e1003376. Bibcode:2014PLSCB..10E3376G. doi:10.1371/journal.pcbi.1003376. ISSN   1553-7358. PMC   3900372 . PMID   24465191.
  4. Geppetto
  5. Takahashi, Dean (30 April 2014). "Openworm is going to be a digital organism in your browser". VentureBeat.
  6. Wood, WB (1988). The Nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press. p. 1. ISBN   978-0-87969-433-3.
  7. Sudhaus W, Kiontke K (2009). "Phylogeny of Rhabditis subgenus Caenorhabditis (Rhabditidae, Nematoda)". Journal of Zoological Systematics and Evolutionary Research. 34 (4): 217–233. doi: 10.1111/j.1439-0469.1996.tb00827.x .
  8. Shadbolt, Peter (21 January 2015). "Scientists upload a worm's mind into a Lego robot". CNN.
  9. "Whole Brain Emulation: No Progress on C. elgans After 10 Years". LessWrong. 1 October 2021.
  10. Kitano, Hiroaki; Hamahashi, Shugo; Luke, Sean (April 1998). "The Perfect C. ELEGANS Project: An Initial Report". Artificial Life. 4 (2): 141–156. CiteSeerX   10.1.1.25.8565 . doi:10.1162/106454698568495. ISSN   1064-5462. PMID   9847421. S2CID   12383326.
  11. Kaufman, Jeff (2 November 2011). "Whole brain emulation and nematodes".
  12. Suzuki, Michiyo; Goto, Takeshi; Tsuji, Toshio; Ohtake, Hisao (2005). "A dynamic body model of the Nematode C. elegans with neural oscillators" (PDF). Journal of Robotics and Mechatronics. 17 (3): 318–326. doi:10.20965/jrm.2005.p0318.
  13. Suzuki, Michiyo; Tsuji, Toshio; Ohtake, Hisao (September 2005). "A model of motor control of the nematode C. elegans with neuronal circuits" (PDF). Artificial Intelligence in Medicine. 35 (1–2): 75–86. doi:10.1016/j.artmed.2005.01.008. ISSN   0933-3657. PMID   16084704.
  14. Frenger, Paul (2005). Simple C. elegans Nervous System Emulator. Houston Conference for Biomedical Engineering Research. p. 192.