Scientist - News - 12-02-2009:
«BackEngineering a multi-functional probiotic Beintema, Nienke A team of students has designed a probiotic bacterium that can exhibit four different health-promoting functions inside the human gut. The students recently won a prize for this achievement at a prestigious international competition. Their results could help pave the way for ‘synthetic probiotics’. Designing an organism at the drawing table, working with the desired functions as a starting point, and then building that organism just like an engineer builds a bridge or a building... It sounds like science fiction, but it is in fact almost a reality. Called ‘synthetic biology’, this principle is rapidly gaining its place in the world of genetic engineering. Its pioneers are using standardized DNA building blocks, or biobricks, which are either isolated from existing organisms or synthetized in a lab. Making rganisms from scratch may not yet be possible, but scientists are already building entirely new metabolic circuits – which is taking ‘regular’ genetic engineering one step further. A student team from the California Institute of Technology (CalTech) used this principle to design a probiotic with four separate health functions. The project was part of the international Genetically Engineered Machine Competition (iGEM), a prestigious competition organized by the Massachusetts Institute of Technology (MIT). Eighty-four teams from all parts of the world participated; CalTech won the third prize. Regulation "As a starting point, we used a commercially available, probiotic strain of E. coli," says project supervisor Christina Smolke, assistant professor at CalTech. "This strain has already been successfully used to treat gastrointestinal disorders, and engineered versions have been developed as anti-HIV and anti-cholera agents. It represents a very suitable chassis for such a sophisticated engineering project." The team managed to incorporate four different functions into the genome of this bacterium: folate (vitamin B11) production; lactase production to combat lactose intolerance; and production of bacteriophage and high levels of hydrogen peroxide, both to fight off infections with pathogens. As a fifth feature, the students designed a system that would allow regulation of these treatment functions by selectively producing renewable subpopulations specialized for each function. The students were able to demonstrate in E. coli the initial steps of each function. "All were tested and confirmed individually," states Smolke, "including the proof of concept of the regulatory system. We did not get to the point of system integration; the time was just too short." The first-time demonstration of these elements individually, however, is already quite significant, underlines Smolke. One of her students will continue working on the project in the future. The results are still quite far from practical application – at least five to ten years, as Smolke estimates. "But if undergraduate researchers can achieve this in only ten weeks’ time," she says, "more focused efforts would certainly allow a project like this to progress much faster. Eventually, I think synthetic biology can play a significant role in probiotic applications." More information: CalTech’s project at the iGEM competition 2008 Groningen Centre for Synthetic Biology Synthetic Biology Community |