Featured Research

from universities, journals, and other organizations

'Two steps' ahead in cystic fibrosis research

Date:
March 12, 2012
Source:
McGill University
Summary:
Restoring normal function to the mutant gene product responsible for cystic fibrosis (CF) requires correcting two distinct structural defects, according to new research. This finding could point to more effective therapeutic strategies for CF in the future.

A recent study led by Gergely Lukacs, a professor at McGill University's Faculty of Medicine, Department of Physiology, and published in the January issue of Cell, has shown that restoring normal function to the mutant gene product responsible for cystic fibrosis (CF) requires correcting two distinct structural defects. This finding could point to more effective therapeutic strategies for CF in the future.

CF, a fatal genetic disease that affects about 60,000 people worldwide, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a membrane protein involved in ion and water transport across the cell surface. As such, CF is characterized by impaired chloride secretion causing the accumulation of viscous mucous that may cause multiple organ dysfunctions, including recurrent lung infection.

The most common mutation in CFTR, known as deltaF508, is caused by a single amino acid deletion and results in a misfolded version of CFTR that is retained within the cell and quickly degrades rather than being trafficked to the cell membrane where it would function as a chloride channel.

In 2005, Lukacs and his lab suggested that deltaF508 mutation effect is not restricted to the domain (the nucleotide binding domain 1 or NBD1, one of five building blocks of CFTR) where the deltaF508 is located. Specifically, his team found that the mutation destabilizes the NBD1 as well as the NBD2 architecture, suggesting that domain-domain interaction plays a critical role in both normal and pathological CFTR folding.

Building on his team's previous work and computer generated models of CFTR, Lukacs and his team set out to determine whether it was possible to correct both NBD1 stability and domain-domain interaction defect. Using a combination of biophysical, biochemical and genetic techniques, the team found that only simultaneous correction of both folding defects was able to ensure normal-like cell surface expression and function of the mutant.

"These findings offer a plausible explanation for the limited efficiency of the available correctors currently under clinical trial. If there are two different folding steps to correct, it is difficult to envision how a single drug could work," explained Lukacs. "The proposed two-step folding model points to the fact that the correction strategy has to be reconsidered."

The study was funded in part by The Cystic Fibrosis Foundation, Cystic Fibrosis Canada, The Canadian Institutes for Health Research (CIHR), Canada Research Chair (CRC) program and the Canada Foundation for Innovation (CFI).


Story Source:

The above story is based on materials provided by McGill University. Note: Materials may be edited for content and length.


Journal Reference:

  1. WaelM. Rabeh, Florian Bossard, Haijin Xu, Tsukasa Okiyoneda, Miklos Bagdany, CoryM. Mulvihill, Kai Du, Salvatore diBernardo, Yuhong Liu, Lars Konermann, Ariel Roldan, GergelyL. Lukacs. Correction of Both NBD1 Energetics and Domain Interface Is Required to Restore ΔF508 CFTR Folding and Function. Cell, 2012; 148 (1-2): 150 DOI: 10.1016/j.cell.2011.11.024

Cite This Page:

McGill University. "'Two steps' ahead in cystic fibrosis research." ScienceDaily. ScienceDaily, 12 March 2012. <www.sciencedaily.com/releases/2012/03/120312114121.htm>.
McGill University. (2012, March 12). 'Two steps' ahead in cystic fibrosis research. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2012/03/120312114121.htm
McGill University. "'Two steps' ahead in cystic fibrosis research." ScienceDaily. www.sciencedaily.com/releases/2012/03/120312114121.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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