OpenWorm is an international

open science Open science is the movement to make scientific research (including publications, data, physical samples, and software) and its dissemination accessible to all levels of society, amateur or professional. Open science is transparent and accessib ...

project for the purpose of simulating 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 Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...

'' at the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

ular 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 A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

and 95

muscle cells A muscle cell, also known as a myocyte, is a mature contractile cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal, smooth, and cardiac (cardiomyocytes). A skeletal muscle cell is long and threadli ...

. This bottom up simulation is being pursued by the OpenWorm community. As of 2014, a

physics engine A physics engine is computer software that provides an approximate simulation of certain physical systems, typically classical dynamics, including rigid body dynamics (including collision detection), soft body dynamics, and fluid dynamics. I ...

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". These maps are available in varying levels of detail. A functional connectome shows connections between various brain ...

and a muscle cell have been created in NeuroML format. A 3D model of the worm

anatomy Anatomy () is the branch of morphology concerned with the study of the internal structure of organisms and their parts. Anatomy is a branch of natural science that deals with the structural organization of living things. It is an old scien ...

can be accessed through the web via the OpenWorm browser. The OpenWorm project is also contributing to develop

Geppetto Geppetto ( ; ) is a fictional character in the 1883 Italian novel ''The Adventures of Pinocchio'' by Carlo Collodi. Geppetto is an elderly, impoverished woodcarver and the creator (and thus 'father') of Pinocchio. He wears a yellow wig resemblin ...

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

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

. __TOC__

Background: ''C. elegans''

The roundworm ''

'' is a free-living, transparent

nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...

, about 1 mm in length, that lives in temperate soil environments. It is the

type species In International_Code_of_Zoological_Nomenclature, 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 spe ...

of its genus. Adult Caenorhabditis elegans

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

hermaphrodite A hermaphrodite () is a sexually reproducing organism that produces both male and female gametes. Animal species in which individuals are either male or female are gonochoric, which is the opposite of hermaphroditic. The individuals of many ...

type possesses only 302 neurons. Furthermore, the structural

of these neurons is fully mapped. There are fewer than one thousand cells in the whole body of a ''C. elegans'' worm, and because ''C. elegans'' is a

model organism A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mo ...

, 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 Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical mic ...

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 In biology and other experimental sciences, an ''in silico'' experiment is one performed on a computer or via computer simulation software. The phrase is pseudo-Latin for 'in silicon' (correct ), referring to silicon in computer chips. It was c ...

'' 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 Smoothed-particle hydrodynamics (SPH) is a computational method used for simulating the mechanics of continuum media, such as solid mechanics and fluid flows. It was developed by Gingold and Monaghan and Lucy in 1977, initially for astrophysic ...

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 compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into th ...

) 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: * 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 Mind uploading is a speculative process of whole brain emulation in which a brain scan is used to completely emulate the mental state of the individual in a digital computer. The computer would then run a simulation of the brain's information ...

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 weights at each of the known synapses. We do not even know whether the synapses are

inhibitory An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a Chemical synapse, postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Inc ...

excitatory In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...

. 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

. 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 In published academic research, publication bias occurs when the outcome of an experiment or research study biases the decision to publish or otherwise distribute it. Publishing only results that show a significant finding disturbs the balance ...

). Indeed, all the biological data the team has gathered is publicly available. By mid-2024, twenty publications made by the group are available for free on their website. All the software that OpenWorm has produced is completely free and open source. OpenWorm website, retrieved September 18, 2024
/ref> 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. Frontiers website, ''OpenWorm: an open-science approach to modeling Caenorhabditis elegans'', article by Balázs Szigeti et al, dated November 3, 2014
/ref>

References

{{Reflist

External links

* Homepage
OpenWorm

OpenWorm community

Milestones

Sibernetic

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