Linking genes with actions, thanks to worms

The wriggling and writhing of worms may hold clues to the inner workings of our brains, according to scientists.

Researchers from the MRC’s Clinical Sciences Centre at Imperial College London have developed a pioneering tool to analyse a worm’s posture as it wriggles.

Using the new tool, the team investigated how exactly the worm’s brain controls its movements. This could give insight into how differences in genes can change neuronal activity in the brains, not just of worms, but of humans too.

Recent advances in technology mean that scientists are now able to gather huge amounts of data about the genes associated with movement and about the activity of nerve cells, or neurons, which drive that activity – whether in worms or in people. But the challenge is to integrate this data with other observations, in a meaningful way.

This new research begins, for the first time, to develop a bigger picture of the whole system of movement, working as one.

The researchers created a library of shapes such that each depicts a key posture adopted by Caenorhabditis elegans (C.elegans) – a type of tiny nematode worm that is a mainstay of scientific research.

C.elegans is the only animal for which scientists have established how all of its neurons are connected. It is also a good model for the human brain because some of the genes that encode its neurons can be found in people, and many of the molecules that its neurons use to communicate with each other, such as dopamine and serotonin, are thought to play similar roles in the human brain.

“Worms are a testing ground,” says Andre Brown, who is head of the Behavioural Genomics group at the Centre and who led the research. “We still don’t know the best ways to measure behaviour.  We think that what we learn from studying worms will also help with more complex organisms, and ultimately influence how we measure human behaviours.”

The worms move by bending sections of their body in turn, to create a wave of movement. Brown and his team have developed an automated camera to track a worm’s movement. It takes 30 static images of the worm’s shape, or posture, every second, to capture even subtle changes.

A computer then assigns the posture a numerical value between 1 and 90, each of which denotes a benchmark posture. The sequence of postures that a worm adopts over time is then represented by a string of numbers.

This numerical data can then be linked to information from separate studies on the worms’ genes and neuronal activity, to try to spot any associations between posture, neuronal activity and genes.

Using such techniques to study the entire process of movement – muscles contracting and relaxing in response to signals from the brain – in worms, they may one day be able to extend them to human movement and other brain processes.

By understanding more about the brain works in a healthy person, the hope is to find clues to what goes wrong in conditions such as depression, anxiety and schizophrenia, though that is a long way off.

The scientists say that their inspiration for studying the building blocks of behaviour came from patterns in language, where words are repeated in different sequences to create sentences. Behaviours, they suggest, are made up of a similar sequence of repeated movements.

Researchers at the MRC’s Laboratory of Molecular Biology in Cambridge, and the European Bioinformatics Institute in Hinxton, worked with Brown on the study published today in PLOS Biology. Together they monitored the movement of 18 strains of worms from across the world, each with slightly different genes. They found that the worms’ postures varied between strains, much as people’s accents can vary between regions.

Linking each worm’s ‘accent’ to the genes of that strain could also hold clues to a better understanding of the genes and neurons behind behaviours. One day, scientists may be able to make similar links in humans.

Read the paper on BiorXiv.

Video: Watch a video showing the range of movements of C.elegans