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UW Scientists Receive $2.5 Million to Explore Bacterial Transcriptomes

Madison, Wisconsin - Some populations of salmonella, once in the intestine, will divide into two subpopulations; one group will remain quiet and hide while the other starts a fight with the host immune system. In response, the immune system wipes everything out — just what the invading bacteria want. With nearly all the bacteria in the intestine wiped out, the hidden subpopulation thrives without competition.


While bacteria reproduce by creating genetic clones, individual bacteria don’t always behave in the same way. Studies have shown that individual bacteria change their behavior to better the odds of their collective survival. How this takes place in bacteria is unknown. But with nearly $2.5 million in funding from the Gordon and Betty Moore Foundation, University of Wisconsin-Madison scientists and collaborators at the University of Southern California and the University of Colorado–Boulder plan to find out by developing the technology necessary for exploring the genetic material of individual bacteria.


The genome, made up of DNA, contains all the instructions needed for a cell to accomplish tasks like growing and adapting. To carry out these instructions, DNA must be transcribed into corresponding molecules of RNA. Those transcripts then allow the cell to “express” or carry out those instructions. The transcriptome represents the complete collection of tasks the cell is working to accomplish.


Bacteria are roughly 100 times smaller than average eukaryotic cells — like animal and plant cells — and carry less messenger RNA (mRNA). To date, no technology exists that can sequence such small amounts of mRNA. Even mRNA sequencing of eukaryotes was only available within the last decade.


To develop the new technology, Edward Ruby, professor of medical microbiology and immunology at the UW School of Medicine and Public Health (UW SMPH), needed a model system with which to experiment.


Ruby and Margaret McFall-Ngai, also a professor of medical microbiology and immunology in the UW SMPH, have been studying the symbiosis between marine squid and bioluminescent bacteria, exploring the processes behind bacterial colonization. The lifelong symbiosis between the bacteria and squid starts with as few as three or four cells coming in contact with the squid and initiating symbiosis.


“With a lot of imaging that McFall-Ngai’s lab has developed, we know that bacteria first attach to the surface of the animal and then migrate into the tissue. We know they sit there for a few hours as if they were thinking about what to do before they move in, and during that thinking process, they’re probably changing their own transcriptome, changing the mRNA that they’re expressing, which will give a clue as to what they’re now preparing themselves to do as they enter the animal’s tissue and set up that mutually beneficial association. This seemed to us a perfect platform for testing.”


Bacteria make these types of transitions as a single cell, and it’s hard to know what a single cell is thinking because they react to environments in different ways, even if they’re clones of the same species, according to Ruby.


“It goes completely against how people think bacteria operate and that clones are all exactly the same. Bacteria are playing all these population-level games, hedging bets in ways we could never see before because we’ve only been studying them as groups of cells,” says Ruby. “But when you start looking at them individually by imaging or, as we hope to do it, transcriptomically, then we can start seeing these strategies. If you know the strategy, you can design approaches to counter those strategies much better.”


Ruby and McFall-Ngai will be collaborating with:

  • Jennifer Reed, UW assistant professor of chemical and biological engineering, who will use metabolic modeling to help predict what changes the bacteria will make to be successful within the squid;
  • Scott Fraser, provost professor of biological sciences and biomedical engineering director of science initiatives at USC, who will lead the development of technology for tracking, harvesting and analyzing the transcriptome of bacteria;
  • Rob Knight, associate professor of chemistry and biochemistry at UC–Boulder, who will organize data produced by the new sequencing platform.

Date Published: 04/24/2013

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UW Scientists Receive $2.5 Million to Explore Bacterial Transcriptomes

Last updated: 04/25/2013
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