Featured Research

from universities, journals, and other organizations

Growing unknown microbes one by one

Date:
June 24, 2014
Source:
California Institute of Technology
Summary:
Trillions of bacteria live in the human body, and although there's plenty of evidence that these microbes play a collective role in human health, we know very little about the individual bacterial species. Employing the use of a specially designed glass chip with tiny compartments, researchers provide a way to target and grow specific microbes from the gut -- a key step in understanding which bacteria are helpful to human health and which are harmful.

Photograph of a glass SlipChip for growing microbes, shown next to a US quarter (left). Fluorescent in situ hybridization image of the target organism (right, top). Transmission electron microscopy image of a single cell of the target organism (right, bottom).
Credit: Liang Ma (Ismagilov group) and Roland Hatzenpichler/Caltech

Trillions of bacteria live in and on the human body; a few species can make us sick, but many others keep us healthy by boosting digestion and preventing inflammation. Although there's plenty of evidence that these microbes play a collective role in human health, we still know very little about most of the individual bacterial species that make up these communities. Employing the use of a specially designed glass chip with tiny compartments, Caltech researchers now provide a way to target and grow specific microbes from the human gut -- a key step in understanding which bacteria are helpful to human health and which are harmful.

The work was published the week of June 23 in the Proceedings of the National Academy of Sciences.

Although a few bacterial species are easy to grow in the laboratory, needing only a warm environment and plenty of food to multiply, most species that grow in and on the human body have never been successfully grown in lab conditions. It's difficult to recreate the complexity of the microbiome -- the entire human microbial community -- in one small plate (a lidded dish with nutrients used to grow microbes), says Rustem Ismagilov, Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering at Caltech.

There are thousands of species of microbes in one sample from the human gut, Ismagilov says, "but when you grow them all together in the lab, the faster-growing bacteria will take over the plate and the slow-growing ones don't have a chance -- leading to very little diversity in the grown sample." Finding slow-growing microbes of interest is like finding a needle in a haystack, he says, but his group wanted to work out a way to "just grow the needle without growing the hay."

To do this, Liang Ma, a postdoctoral scholar in Ismagilov's lab, developed a way to isolate and cultivate individual bacterial species of interest. He and his colleagues began by looking for bacterial species that contained a set of specific genetic sequences. The targeted gene sequences belong to organisms on the list of "Most Wanted" microbes -- a list developed by the National Institutes of Health (NIH) Human Microbiome Project. The microbes carrying these genetic sequences are found abundantly in and on the human body, but have been difficult to grow in the lab.

To grow these elusive microbes, the Caltech researchers turned to SlipChip, a microfluidic device previously developed in Ismagilov's lab. SlipChip is made up of two glass slides, each the size of a credit card, that have tiny etched grooves which become channels when the grooved surfaces are stacked atop one another. When a sample -- say, a jumbled-up assortment of bacteria species collected from a colonoscopy biopsy -- is added to the interconnected channels of the SlipChip, a single "slip" of the top chip will turn the channels into individual wells, with each well ideally holding a single microbe. Once sequestered in an isolated well, each individual bacterium can divide and grow without having to compete for resources with other types of faster-growing microbes.

The researchers then needed to determine which compartment of the SlipChip contained a colony of the target bacterium -- which is not a simple task, says Ismagilov. "It's a Catch-22 -- you have to kill the organism in order to find its DNA sequence and figure out what it is, but you want a live organism at the end of the day, so that you can grow and study this new microbe," he says. "Liang solves this in a really clever way; he grows a compartment full of his target microbe in the SlipChip, then he splits the compartment in half. One half contains the live organism and the other half is sacrificed for its DNA to confirm that the sequence is that of the target microbe."

The method of creating two halves in each well in the SlipChip will be published separately in an upcoming issue of the journal Integrative Biology.

To validate the new methodology, the researchers isolated one specific bacterium from the Human Microbiome Project's "Most Wanted" list. The investigators used the SlipChip to grow this bacterium in a tiny volume of the washing fluid that was used to collect the gut bacteria sample from a volunteer. Since bacteria often depend on nutrients and signals from the extracellular environment to support growth, the substances from this fluid were used to recreate this environment within the tiny SlipChip compartment -- a key to successfully growing the difficult organism in the lab.

After growing a pure culture of the previously unidentified bacterium, Ismagilov and his colleagues obtained enough genetic material to sequence a high-quality draft genome of the organism. Although a genomic sequence of the new organism is a useful tool, further studies are needed to learn how this species of microbe is involved in human health, Ismagilov says.

In the future, the new SlipChip technique may be used to isolate additional previously uncultured microbes, allowing researchers to focus their efforts on important targets, such as those that may be relevant to energy applications and the production of probiotics. The technique, says Ismagilov, allows researchers to target specific microbes in a way that was not previously possible.


Story Source:

The above story is based on materials provided by California Institute of Technology. The original article was written by Jessica Stoller-Conrad. Note: Materials may be edited for content and length.


Journal Reference:

  1. L. Ma, J. Kim, R. Hatzenpichler, M. A. Karymov, N. Hubert, I. M. Hanan, E. B. Chang, R. F. Ismagilov. Gene-targeted microfluidic cultivation validated by isolation of a gut bacterium listed in Human Microbiome Project's Most Wanted taxa. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1404753111

Cite This Page:

California Institute of Technology. "Growing unknown microbes one by one." ScienceDaily. ScienceDaily, 24 June 2014. <www.sciencedaily.com/releases/2014/06/140624093324.htm>.
California Institute of Technology. (2014, June 24). Growing unknown microbes one by one. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2014/06/140624093324.htm
California Institute of Technology. "Growing unknown microbes one by one." ScienceDaily. www.sciencedaily.com/releases/2014/06/140624093324.htm (accessed August 28, 2014).

Share This




More Plants & Animals News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Australian Sheep Gets Long Overdue Haircut

Raw: Australian Sheep Gets Long Overdue Haircut

AP (Aug. 28, 2014) Hoping to break the record for world's wooliest, Shaun the sheep came up 10 pounds shy with his fleece weighing over 50 pounds after being shorn for the first time in years. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Minds Blown: Scientists Develop Fish That Walk On Land

Minds Blown: Scientists Develop Fish That Walk On Land

Newsy (Aug. 28, 2014) Canadian scientists looking into the very first land animals took a fish out of water and forced it to walk. Video provided by Newsy
Powered by NewsLook.com
Super Healthful Fruits and Vegetables: Which Are Best?

Super Healthful Fruits and Vegetables: Which Are Best?

Ivanhoe (Aug. 27, 2014) We all know that it is important to eat our fruits and vegetables but do you know which ones are the best for you? Video provided by Ivanhoe
Powered by NewsLook.com
Bad Memories Turn Good In Weird Mouse Brain Study

Bad Memories Turn Good In Weird Mouse Brain Study

Newsy (Aug. 27, 2014) MIT researchers were able to change whether bad memories in mice made them anxious by flicking an emotional switch in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins