MIT researchers are using sensors, memory switches, and circuits to enable a common bacterium found in the gut to detect certain diseases and immune disorders.
This MIT illustration shows Bacteroides thetaiotaomicron (white) living on cells in the gut (large pink cells coated in microvilli) and being activated by added chemical signals (small green dots) to express specific genes, such as those encoding light-generating luciferase proteins (glowing bacteria). (Image courtesy of MIT)
When it comes to bacteria, not all types are our enemy. Some bacteria can even be exploited for the forces of good. So what if we could find a way to upgrade some of these "friendly" bacteria--programming them to detect some of the cancers and infectious diseases that cross their path to enable early treatment?
Researchers from MIT believe they've developed basic computing elements that could make such a reality possible. In a recent project, researchers created a series of sensors, memory switches, and circuits that can be encoded in a common human bacterium found in the intestines known as Bacteroides thetaiotaomicron. Their research indicates that these basic computing elements will allow the bacteria to sense, memorize, and respond to signals from the bacteria that could lead to early detection and treatment of inflammatory bowel disease and colon cancer.
This research falls on the heels of previous work surrounding the construction of genetic circuits inside various forms of bacteria such as E. coli, but these strains are only present in the intestines at extremely low levels. Their low presence ultimately makes them less helpful if reprogrammed to do good. Instead, the team chose to work with Bacteroides thetaiotaomicron because of its seemingly ubiquitous presence in most human intestinal tracts.
The first step involved developing a series of genetic parts that are used to specifically program gene expression inside the bacteria. They then built four sensors that can be encoded in the bacterium's DNA to respond to a signal, before switching genes on and off in the bacterium. However, the true novelty of their research lies in the ability to enable the bacterium to sense and report on pathologies in the intestines, like signs of inflammation or bleeding.
To do this, researchers equipped the bacterium with a form of genetic memory using a class of enzymes known as recombinases. These enzymes can record information picked up by bacterial DNA by recognizing specific DNA addresses and inverting their direction. They then tested their set of genetic tools within the Bacteroides thetaiotaomicron in mice, and found that when fed food containing the right ingredients, the bacteria could remember what the mice ate.
The team hopes to expand their research into different species of Bacteroides, as the microbial makeup of the human intestines will vary from person to person. This will help make the process more adaptable, and could eventually help researchers apply the concept of microbes sensing and responding to signs of disease elsewhere in the body.
Ultimately the team believes that more advanced genetic computing circuits could be built in the future in effort to create a whole new line of noninvasive diagnostic and therapeutic mechanisms.
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Kristopher Sturgis is a contributor to Qmed and MPMN.
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