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

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 wiredhow its genes and the molecules that regulate them are relatedso 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.


Contact: Hannah Krakauer
Seattle Biomedical Research Institute

Related biology technology :

1. Palatin Technologies, Inc. to Report Fiscal Year 2012 First Quarter Results; Teleconference and Webcast to be held on November 15, 2011
2. Avaxia Biologics, Inc. Raises $2.2 Million in First Closing of Series A Financing to Advance Oral Antibodies for Inflammatory Bowel Disease
3. Palatin Technologies, Inc. Reports First Quarter Fiscal Year 2012 Results; Teleconference and Webcast to be held on November 15, 2011
4. Fitzsimons Redevelopment Authority Rolls Out First Phase of Strategic Refocus With Appointment of Four Key Leaders in The Bioscience Industry to Its Board of Directors
5. Webcor Builders Selected as the General Contractor for First Phase of LA BioMeds New Campus Master Plan
6. China Cord Blood Corporation to Report Second Quarter and First Half of Fiscal 2012 Financial Results
7. Tiger Woods Gives Exclusive First Interview Since POWERED by FUSE Announcement!
8. The Pharmabiotic Research Institute (PRI) is Preparing to Publish its First Works on the Therapeutic and Medicinal Potential of Probiotics
9. Eye Surgery Center of Michigan First in Southeast Michigan to Perform Bladeless Cataract Surgery Using New LenSx® Laser Technology
10. Amgen Announces 2012 First Quarter Dividend
11. Varian Medical Systems Schedules First Quarter FY2012 News Release and Conference Call
Post Your Comments:
(Date:11/24/2015)... KUALA LUMPUR, Malaysia , Nov. 24, 2015 ... the global contract research organisation (CRO) market. The ... to result in lower margins but higher volume ... With increased capacity and scale, however, margins in ... Contract Research Organisation (CRO) Market ( ...
(Date:11/24/2015)... Worcester, Mass. (PRWEB) , ... November 24, 2015 ... ... need to maintain healthy metabolism. But unless it is bound to proteins, copper ... Institutes of Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a ...
(Date:11/24/2015)... , ... November 24, 2015 , ... This fall, global ... competitive events in five states to develop and pitch their BIG ideas to improve ... each state are competing for votes to win the title of SAP's Teen Innovator, ...
(Date:11/24/2015)... , Nov. 24, 2015 /PRNewswire/ - Aeterna ... announced today that the remaining 11,000 post-share consolidation ... Purchase Warrants (the "Series B Warrants") subject to ... exercised on November 23, 2015, which will result ... After giving effect to the issuance of such ...
Breaking Biology Technology:
(Date:11/19/2015)... Nov. 19, 2015  Although some 350 companies are ... by a few companies, according to Kalorama Information. These include ... of the market share of the 6.1 billion-dollar molecular ... World Market for Molecular Diagnostic s .    ... is still controlled by one company and only a ...
(Date:11/18/2015)... , November 18, 2015 ... has published a new market report titled  Gesture Recognition ... and Forecast, 2015 - 2021. According to the report, the global ... and is anticipated to reach US$29.1 bn by 2021, ... North America dominated the ...
(Date:11/17/2015)... , November 17, 2015 ... 19 novembre  2015.  --> Paris , ... --> DERMALOG, le leader de l,innovation biométrique, a ... fois passeports et empreintes sur la même surface de ... passeports et l,autre pour les empreintes digitales. Désormais, un ...
Breaking Biology News(10 mins):