Awards Database

Scialog: Collaborative Teams - 2015

Raghuveer  Parthasarathy

Raghuveer Parthasarathy

Physics, University of Oregon

Brian Hammer

Biology, Georgia Institute of Technology

Joao B. Xavier

Biology, Memorial Sloan Kettering Cancer Center

Rebooting the Gut Microbial Ecosystem using Bacterial Dueling

What determines the stability of multi-species ecosystems, and how might a community be supplanted by invaders? This fundamental scientific question doesn’t just apply to animal and plant species but also to competing species of bacteria.

There has been a lot in the press recently about “probiotics,” the gut-dwelling microorganisms believed to provide health benefits when consumed and allowed to thrive in a rich – and, one hopes, properly balanced – internal ecosystem.

Inspired by recent research revealing the health benefits of microbiota in the gut, researchers Raghuveer Parthasarathy, physics, University of Oregon; Brian Hammer, biology, Georgia Institute of Technology; and Joao B. Xavier, computational biology, Memorial Sloan Kettering Cancer Center, New York City, have embarked on a long-term project to “personalize” the microbial communities in our stomachs and intestines, tailoring them to specific health and medical needs.

The first step in this quest is to come up with a way to “reboot” the system, as it were. And, because this is a basic research project seeking to advance our knowledge, Parthasarathy, Hammer and Xavier hope to answer the big question above as it pertains to bacteria.

Their first move will make use of a microbe skilled at “community displacement.” Vibrio cholerae is a comma-shaped bacterium, some strains of which cause cholera. An ages-old plague on humanity, the disease brings severe diarrhea and dehydration; as late as 2010 cholera is estimated to have afflicted three- to five-million victims and killed 58,000 to 100,000.

“The bacterium is notorious for its toxin-mediated ‘flushing’ of the intestine,” the researchers observed. However, rather than focusing on its disease inducing effects, they hope to make use of its ability to efficiently colonize “chitinous” surfaces in the environment. Chitin, from the Greek chiton, meaning “covering,” is a cellulose-like material found in many organisms – in butterfly wings as well as the cell walls of fungi, and in the shells of crabs, lobsters and shrimp.

For their experiments, Parthasarathy, Hammer and Xavier will use the larval zebrafish, which has plenty of chitinous material in its tiny gut, as a model organism. As it competes with other microbes for nutrients, Vibrio cholerae, an aggressive bacteriuminteracts by direct contact with other bacteria in a process microbiologists have labeled “dueling behavior.” Vibrio cholerae extends a hollow sheath containing a deadly protein molecule, injecting it into its cellular victim.

As they manipulate the various genetic and ecological factors that activate Vibrio cholerae’s dueling behavior, the researchers will use fluorescence microscopy, a process that attaches light-absorbing and emitting molecules to key sites within the sample. This is expected to yield three-dimensional and time-related data about Vibrio’s“community displacement” skills. Xavier will then use the experimental data to develop mathematical models of the bacterium’s aggressive behavior and its ability to purge the zebrafish larva’s normal gut community.

Assuming that works – and there are no guarantees in fundamental research such as this – their next major project will be to reboot the ecosystem with a new microbial community. To do this, they will genetically programVibrio cholerae to self-destruct once it has accomplished its task. Next they will assemble new communities of microbiota likely to displace the remaining Vibrio cholerae.

If successful, their work could open new avenues for balancing and controlling the several hundred species of bacteria in the human gut, providing new ways to maintain human health.

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