(Image: Thomas Deernick, NCMIR/Science Photo Library)
In a move that promises to bring the advantages of computer aided design (CAD) to genetic engineers, the first computer model of a complete bacterium has been produced in the US. It means researchers will soon be able to modify models of an organism’s genome on a computer screen - or create artificial lifeforms - without the risks of undertaking wet biology in secure biosafety labs.
The pathogen is called Mycoplasma genitalium, a bacterium implicated in a number of urethral and vaginal infections. The bug was ripe for modelling say researchers at Stanford University in California, because it has the smallest genome of any free-living organism, with just 525 genes. By contrast, the popular lab pathogen E. coli has 4288 genes.
The modelling was undertaken by bioengineer Markus Covert and colleagues. To get the raw data for their model, they undertook an exhaustive literature review - spanning 900 research papers - to allow them to program into their model some 1900 experimentally observed behaviours and molecular interactions that M. genitalium can take part in during its life cycle.
In software terms, they found the behaviours of the 525 genes could be described by 28 algorithms, each governing the behaviour of a software module modelling a different biological process. “These modules then communicated with each other after every time step, making for a unified whole that closely matched M. genitalium's real-world behaviour,” claims the Stanford team in a statement. Their research appears in the journal Cell (doi: 10.1016/j.cell.2012.05.044).
Such models will ultimately give biologists the freedom to undertake “what if” scenarios common in regular engineering - changing parameters in a genome design, say, like a civil engineer adjusts the width of a bridge deck on a computer to see what happens. As well as being experimentally useful, allowing artificial organisms and synthetic lifeforms to be created virtually (harming no-one), they could also boost biosafety by preventing accidental creations of lethal pathogens. In 2001, for instance, researchers in Australia accidentally created a lethal strain of mousepox.
In a commentary article in Cell, systems biologists Peter Freddolino and Saeed Tavazoie of Columbia University say they hope the work will soon be extended to more commonly used lab bugs like E. coli - but also warn that the technique’s accuracy has yet to be demonstrated. It is unclear, they say, “how well overall behaviors will be predicted from a collection of separately obtained parameters” gleaned from hundreds of research papers.
But the US National Institutes of Health, which funded the modelling work, is excited. It believes the model a major step towards finding “new approaches for the diagnosis and treatment of disease”, says James Anderson, an NIH program director.t