The Gordon and Betty Moore Foundation and Research Corporation for Science Advancement awarded 5 grants totaling $731k to teams of researchers pursuing "ambitious, high-risk, highly impactful discovery research on untested ideas in physical cell biology."

One of the winning teams—composed of Brian Hammer (Georgia Tech), Raghuveer Parthasarathy (University of Oregon) and Joao Xavier (Memorial Sloan-Kettering Cancer Center)—proposed a long term project titled, “Rebooting the Gut Microbial Ecosystem using Bacterial Dueling”. 

Studies abound linking particular diseases, such as Crohn’s, to the bacteria in our gut. Their project aims to demonstrate that bacterial dueling can be used to eliminate harmful bacteria in the gut and repopulate it with healthy bacteria. 

To begin, the researchers will introduce vibrio cholerae into a sample of zebrafish. V. cholera is an aggressive bacterium that feeds on chitin, a complex carbohydrate and major component of exoskeletons. Zebrafish, a common sight in home aquariums, is an excellent model organism that also happens to have a taste for chitin-rich zooplankton. 

When chitin is ingested, some of the sugars are released and sensed by V. cholera, which turns on its dueling machinery. 

“What this means is that the response to chitin results in the production of a special protein factor (a transcription factor) in each Vibrio cholerae cell that can turn on the dueling machinery,” Dr. Hammer explained. “We can also genetically engineer Vibrio cholerae cells so that this special factor is always produced. These cells do not need chitin to activate dueling; it's on all the time.” Woe unto any microbe squatting alongside V. cholerae. 

Interestingly, some strains of V. cholerae are especially bellicose, keeping their dueling machinery armed at all times, no chitin required. 

Using fluorescent microscopy, the scientists will observe and subsequently model V. cholerae’s behavior under various conditions—by using different strains of V. cholerae (those that need chitin and those that are always battle-ready) and by manipulating the presence of chitin and other food sources.

For this research to ever have therapeutic applications, V. cholerae must be kept from running amok. Accordingly, the team plans to design a strain of V. cholerae with an off-switch. Hammer elaborated, “Basically, we engineer the cells so that they can only grow if provided an essential factor (a chemical we can add) for their cell wall. If we add that chemical to flasks of cells in the lab, and presumably into the water with the fish, the Vibrios grow normally. To make the cells self-destruct we simply remove that chemical from the water or move the fish into new water lacking that chemical.”

The last step in this study will be to repopulate the zebrafish’s gut with microbes found in healthy zebrafish. 

If successful it “would suggest that we can develop dueling bacteria that could be used in humans to replace harmful bacteria in the gut with healthy ones… Finally, what I think is also really cool about our study is that [by manipulating chitin in the fish’s diet] it may also link the food we eat to how gut microbes interact,” beamed Hammer.