Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

“Two steps” ahead in cystic fibrosis research

13.03.2012
New research could provide roadmap for more effective drug discovery for CF
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).

For more information on the study, please visit:
http://www.cell.com/abstract/S0092-8674(11)01368-7

Allison Flynn | EurekAlert!
Further information:
http://www.mcgill.ca

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>