Featured Research

from universities, journals, and other organizations

Novel Genetic Screens Provide Panoramic Views Of Cellular Systems

Date:
October 28, 2008
Source:
Harvard Medical School
Summary:
Researchers often use the technique of RNA interference to identify genes involved in particular biological processes by knocking them down, one at a time, and observing the result. But this approach fails to capture some key players because many genes are redundant. Thus, cells can mask their distress when they lose a single gene by turning to fail-safes with the same function. A team has now overcome this obstacle, using RNAi to systematically knock down pairs of genes in fruit fly cells.

Despite the rise of systems biology, many geneticists continue to probe genes in isolation. They even use cutting-edge RNA interference (RNAi) technology to knock down one gene at a time. This approach often yields a narrow view of cellular systems.

Now, researchers at Harvard Medical School, the Institute for Cancer Research, and the Institut de Biologia Molecular de Barcelona have widened the lens, using RNAi to systematically knock down pairs of genes in fruit fly cells. The findings appear in the Oct. 17 issue of Science.

"Data from our novel double RNAi screens provide panoramic views of cellular processes," says senior author Norbert Perrimon, who is an HMS professor of genetics and an investigator with Howard Hughes Medical Institute. "By using this approach to expose interactions between genes, researchers may accelerate the pace of discovery in systems biology and advance personalized medicine."

In a typical RNAi screen, researchers begin with a library of short interfering RNAs (siRNAs) targeting specific genes. Each siRNA disrupts the gene's ability to produce a particular protein. Scientists place the siRNAs on thousands of cells, with just one gene being targeted in each well of cells. Then they watch the cells and record changes.

But this approach fails to capture some key players because many genes are redundant. Thus, cells can mask their distress when they lose a single gene by turning to fail-safes with the same function. Perrimon's approach overcomes this obstacle.

"If you take one part out of a plane engine, it still works, but if you take out that part plus its fail-safe, then you're in trouble," explains corresponding author Chris Bakal, a postdoctoral research in the Perrimon lab.

Bakal began with a traditional RNAi screen for genes that play a role in a cell's stress response, generating a list of genes that help the cell decide whether to die, move, or take some other action in a stressful environment. But Bakal noticed that some key players—genes identified by other labs via a different method—were missing from the list.

He selected 12 of these "suspects," including a tumor-suppressor gene called PTEN, for further study. Bakal knocked down PTEN and used the resulting cells to perform another massive RNAi screen. Thus, he performed the screen in the context of a defective tumor suppressor. The stress response results were very different from the original screen. He performed similar double-knock-down screens with the 11 other suspects. In total, he tested 17,724 different combinations in the same cell type.

"A given gene behaved differently, depending on the genetic context," says Bakal. "Our approach highlights the connections between genes, telling a more complete story."

His data indicate how specific genes interact and how they influence each other. Bakal says researchers can use this approach to map cellular systems and make predictions about the behavior of particular genes, which has direct implications for personalized medicine. Clinicians must understand a patient's genetic context before making medical decisions based on his or her DNA sequence. In the future, physicians may turn to double RNAi screen results when reading genomes.

This study is funded by Howard Hughes Medical Institute, Genome Canada, the European Union, and the Leukemia and Lymphoma Society. The authors report no conflicts of interest.


Story Source:

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


Journal Reference:

  1. Bakal et al. Phosphorylation Networks Regulating JNK Activity in Diverse Genetic Backgrounds. Science, 2008; 322 (5900): 453 DOI: 10.1126/science.1158739

Cite This Page:

Harvard Medical School. "Novel Genetic Screens Provide Panoramic Views Of Cellular Systems." ScienceDaily. ScienceDaily, 28 October 2008. <www.sciencedaily.com/releases/2008/10/081016141419.htm>.
Harvard Medical School. (2008, October 28). Novel Genetic Screens Provide Panoramic Views Of Cellular Systems. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2008/10/081016141419.htm
Harvard Medical School. "Novel Genetic Screens Provide Panoramic Views Of Cellular Systems." ScienceDaily. www.sciencedaily.com/releases/2008/10/081016141419.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
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