OpenWorm is an international open science project for the purpose of

simulating A simulation is the imitation of the operation of a real-world process or system over time. Simulations require the use of models; the model represents the key characteristics or behaviors of the selected system or process, whereas the s ...

the roundworm ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

'' at the cellular level. 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. As of 2014, a physics engine called Sibernetic has been built for the project and models of the neural

connectome A connectome () is a comprehensive map of neural connections in the brain, and may be thought of as its " wiring diagram". An organism's nervous system is made up of neurons which communicate through synapses. A connectome is constructed by t ...

and a muscle cell have been created in

NeuroML NeuroML is an XML (Extensible Markup Language) based model description language that aims to provide a common data format for defining and exchanging models in computational neuroscience. The focus of NeuroML is on models which are based on the bio ...

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, a web-based multi-algorithm, multi-scale simulation platform engineered to support the simulation of the whole organism. __TOC__

Background: ''C. elegans''

The roundworm ''

'' is a free-living, transparent nematode, about 1 mm in length, that lives in temperate soil environments. It is the

type species In zoological nomenclature, a type species (''species typica'') is the species name with which the name of a genus or subgenus is considered to be permanently taxonomically associated, i.e., the species that contains the biological type specimen( ...

of its genus. Adult Caenorhabditis elegans

''C. elegans'' has one of the simplest nervous systems of any organism, with its

hermaphrodite In reproductive biology, a hermaphrodite () is an organism that has both kinds of reproductive organs and can produce both gametes associated with male and female sexes. Many taxonomic groups of animals (mostly invertebrates) do not have ...

type having only 302 neurons. Furthermore, the structural

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. By manipulating the neurons through optogenetic techniques, combined with the above recording capacities the project is in an unprecedented position to be able to fully characterize the neural dynamics of an entire organism. In the process of trying to build an "in silico" model of a relatively simple organism like ''C. elegans'', new tools are being developed which will make it easier to model progressively more complex organisms.

OpenWorm project

Although the ultimate goal is to simulate all features of ''C. elegans behaviour, the project is new and the first behaviour the OpenWorm community decided to simulate is a simple motor response: teaching the worm to crawl. To do so, the virtual worm must be placed in a virtual environment. A full feedback loop must be 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 Hydrodynamic 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 Digestion is the breakdown of large insoluble food molecules into small water-soluble food molecules so that they can be absorbed into the watery blood plasma. In certain organisms, these smaller substances are absorbed through the small intest ...

) 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

. 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: * Approximate the synapses which synapse on those neurons * Repeat the process for other muscle cells

Progress

, 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". , a whole brain emulation has not yet been achieved.

Related projects

In 1998 Japanese researchers announced the Perfect C. elegans Project. A proposal was submitted, but the project appears to have been abandoned. 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. 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. 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 weight In neuroscience and computer science, synaptic weight refers to the strength or amplitude of a connection between two nodes, corresponding in biology to the amount of influence the firing of one neuron has on another. The term is typically used in ...

s 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.

References

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External links

* Homepage
OpenWorm

OpenWorm community

Milestones

Sibernetic

Geppetto
Artificial life Free biosimulation software Open science Software using the MIT license Neuroinformatics