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Taking Apart Cholera

In 2001, when the National Science Foundation called for interdisciplinary research proposals, Dartmouth's Ronald Taylor, Kathryn Cottingham, and Deborah Chiavelli combined their ecological and genetic approaches to studying cholera and applied for the grant. They were awarded the money to begin their quest to learn how cholera responds to changes in the environment and to understand how that affects people living in an area where cholera outbreaks are a seasonal threat.

L-R: Chiavelli, Taylor, and Cottingham
L-R: Chiavelli, Taylor, and Cottingham (photo by Joseph Mehling '69)

Taylor, professor of microbiology and immunology at Dartmouth Medical School, Cottingham, associate professor of biology, and Chiavelli, a post-doctoral researcher, along with collaborators at the University of Maryland and in Bangladesh, are practically taking apart, gene by gene, Vibrio cholerae, the bacterium that causes cholera.

"Our group has ecologists, a statistician, a geneticist, and two microbiologists," says Chiavelli. "Without experts in all of these fields, we would not be able to look for the genetic mechanisms behind the bacterial processes that drive the observed ecological and epidemiological patterns."

The Dartmouth group wants to learn how cholera interacts with its two basic environments: the natural outdoors, where it can be found in freshwater ecosystems either on its own or sticking to plankton, and the environment inside a human intestine, where it causes diarrhea, dehydration, and sometimes death.

"The reason I'm so interested in cholera is because I feel I can make a difference, which is rare for an ecologist," says Cottingham. "Cholera occurs regularly in developing countries like Bangladesh and India, and, hopefully, my work someday will help people who get this disease."

"Being on this team makes me a better biology department citizen. I now have a much greater understanding of the questions my colleagues in molecular biology, cell biology, and genetics are asking."

- Kathryn Cottingham

The first obstacle Taylor, Cottingham, and Chiavelli had to overcome, however, was learning how to communicate with each other. They spent many hours teaching each other nuances of conducting science from both ecological and genetic points of view.

"Our first year, we spent a lot of time learning each other's languages," says Cottingham. "Ron learned about ecology, and Deb and I learned about genetics."

In addition to time invested in reciprocal education, the team developed the methodology needed to conduct their investigation. They employed micro-arrays, a tool that displays the whole genome of an organism one gene at a time. Since no commercial arrays of V. cholerae exist, as they do for people, rats, and some plant species, the Dartmouth researchers created their own. After the researchers purchase snippets of genes created from the known genome sequence from a bioinformatics company, a Dartmouth-owned machine creates the microarray. The scientists then take RNA, also harvested from V. cholerae, and use it on the microarray to determine what genes are activated under various conditions.

"Messenger RNA is produced when a gene is transcribed. The more messenger RNA, the more that particular gene is currently being expressed," says Chiavelli.

The group is gaining traction in learning how cholera reacts to changes in the environment, how it responds when attached to plankton, and how cholera bacteria act when they are deprived of food or nutrients. The researchers say the interdisciplinary work done thus far has been rewarding.

"Being on this team makes me a better biology department citizen," says Cottingham. "I now have a much greater understanding of the questions my colleagues in molecular biology, cell biology, and genetics are asking."

- By Susan Knapp

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Last Updated: 5/30/08