Featured Research

from universities, journals, and other organizations

First comprehensive regulatory map is a blueprint for how to defeat tuberculosis

Date:
July 3, 2013
Source:
Seattle Biomedical Research Institute (Seattle BioMed)
Summary:
Researchers have taken the first steps toward a complete representation of the regulatory network for Mycobacterium tuberculosis. This map will yield unique insights into how the bacteria survive in the host.

Despite decades of research on the bacterium that causes tuberculosis (TB), scientists have not had a comprehensive understanding of how the bacterium is wired to adapt to changing conditions in the host. Now, researchers at Stanford University, Seattle BioMed, Boston University and the Broad Institute, Max Planck Institute of Biology in Berlin, Germany, Caprion Proteomics Inc. in Montreal, Canada, Brigham and Woman's Hospital (Harvard University), and Colorado State University have taken the first steps toward a complete representation of the regulatory network for Mycobacterium tuberculosis.

This map of the network of genes that control the TB bacterium will yield unique insights into how the bacteria survive in the host, and how they can be tackled with new drug interventions. The landmark results are published this week in the journal Nature.

The burden of tuberculosis

One third of the world's population is latently infected with TB, harboring the bacteria in a dormant form in the lungs. In 2011 alone, 8.7 million people fell ill with the active form of TB, and 1.4 million died.

For hundreds of years, people have associated reduced oxygen tension with the control of TB. Artificially collapsing an infected lung using a pneumothorax device, or inserting golf ball-sized items into the pleural cavity, were common ways to treat the disease before the rise of antibiotics. Despite the prevalence of these treatment methods, the bacteria appeared to survive in the host, even in hypoxic environments.

"We needed a window into how tuberculosis adapts to change, whether that is a lack of oxygen or a new drug," explains David Sherman, Ph.D., a lead researcher from Seattle BioMed. "In order to do that, we needed to understand how TB is wired -- how its genes and the molecules that regulate them are related -- so we can see how it changes its behavior depending on the environment."

Mapping tuberculosis

In order to create a map of how TB genes are regulated, researchers led by Gary K. Schoolnik, Ph.D., at the Stanford Medical School, David Sherman, Ph.D., of Seattle BioMed and James E. Galagan, Ph.D., of Boston University and the Broad Institute, turned to technologies that identified the key players in the system. Using ChIP-Seq, a method to analyze how proteins interact with DNA, they identified where 50 of TB's regulatory transcription factors bound to DNA, thereby providing the wiring diagram of genetic connections.

Though this kind of linking of transcription factors to genes had been done piecemeal in the past, Sherman explains, this is the first time that such a comprehensive study has been done all at once. "Nobody has ever done ChIP-Seq for every transcription factor in an organism," he says. "This is a far more global view of one organism's wiring than anyone has ever achieved before."

Creating a road map for future interventions

Because the regulatory map yields a systems view of how different genes in the TB bacterium interact, it will be useful to virtually everyone who studies TB, says Sherman. The network provides key insights into the relative regulatory importance of some genes, and yields unexpected relationships between others.

"Everyone who studies TB can now look at this wiring diagram and gain a better understanding of how their favorite genes relate in a larger context," he says. "Suddenly, we can see how different areas connect, in intimate and important detail."

Though this map is the most comprehensive to date, Sherman and his colleagues plan to fill it out even further by incorporating the sequences of the remaining transcription factors and their relationship to the TB genome. The map will eventually provide a window into how targeted drugs or immunological interventions could interfere with TB's ability to survive in the host, adding a critical weapon to the fight against TB's worldwide devastation.

This project has been funded in whole with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800059C. We are grateful for their support, making this scientific research project possible.


Story Source:

The above story is based on materials provided by Seattle Biomedical Research Institute (Seattle BioMed). Note: Materials may be edited for content and length.


Journal Reference:

  1. James E. Galagan, Kyle Minch, Matthew Peterson, Anna Lyubetskaya, Elham Azizi, Linsday Sweet, Antonio Gomes, Tige Rustad, Gregory Dolganov, Irina Glotova, Thomas Abeel, Chris Mahwinney, Adam D. Kennedy, Renι Allard, William Brabant, Andrew Krueger, Suma Jaini, Brent Honda, Wen-Han Yu, Mark J. Hickey, Jeremy Zucker, Christopher Garay, Brian Weiner, Peter Sisk, Christian Stolte, Jessica K. Winkler, Yves Van de Peer, Paul Iazzetti, Diogo Camacho, Jonathan Dreyfuss, Yang Liu, Anca Dorhoi, Hans-Joachim Mollenkopf, Paul Drogaris, Julie Lamontagne, Yiyong Zhou, Julie Piquenot, Sang Tae Park, Sahadevan Raman, Stefan H. E. Kaufmann, Robert P. Mohney, Daniel Chelsky, D. Branch Moody, David R. Sherman, Gary K. Schoolnik. The Mycobacterium tuberculosis regulatory network and hypoxia. Nature, 2013; DOI: 10.1038/nature12337

Cite This Page:

Seattle Biomedical Research Institute (Seattle BioMed). "First comprehensive regulatory map is a blueprint for how to defeat tuberculosis." ScienceDaily. ScienceDaily, 3 July 2013. <www.sciencedaily.com/releases/2013/07/130703135846.htm>.
Seattle Biomedical Research Institute (Seattle BioMed). (2013, July 3). First comprehensive regulatory map is a blueprint for how to defeat tuberculosis. ScienceDaily. Retrieved September 3, 2014 from www.sciencedaily.com/releases/2013/07/130703135846.htm
Seattle Biomedical Research Institute (Seattle BioMed). "First comprehensive regulatory map is a blueprint for how to defeat tuberculosis." ScienceDaily. www.sciencedaily.com/releases/2013/07/130703135846.htm (accessed September 3, 2014).

Share This



More Health & Medicine News

Wednesday, September 3, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) — You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) — The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Doctors Fear They're Losing Battle Against Ebola

Doctors Fear They're Losing Battle Against Ebola

AP (Sep. 2, 2014) — As a third American missionary is confirmed to have contracted Ebola in Liberia, doctors on the ground in West Africa fear they're losing the battle against the outbreak. (Sept. 2) Video provided by AP
Powered by NewsLook.com
Tech Giants Bet on 3D Headsets for Gaming, Healthcare

Tech Giants Bet on 3D Headsets for Gaming, Healthcare

AFP (Sep. 2, 2014) — When Facebook acquired the virtual reality hardware developer Oculus VR in March for $2 billion, CEO Mark Zuckerberg hailed the firm's technology as "a new communication platform." Duration: 02:24 Video provided by AFP
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