Featured Research

from universities, journals, and other organizations

Knockouts in human cells point to pathogenic targets

Date:
November 27, 2009
Source:
Whitehead Institute for Biomedical Research
Summary:
Researchers have developed a new approach for genetics in human cells and used this technique to identify specific genes and proteins required for pathogens. With the ability to generate knockout cells for most human genes, the authors were able to find genes used by pathogens to enter and kill human cells. The identification of such factors could aid the future development of new therapeutics to combat infectious disease.

Whitehead researchers have developed a new type of genetic screen for human cells to pinpoint specific genes and proteins used by pathogens, according to their paper in Science.

In most human cell cultures genes are present in two copies: one inherited from the father and one from the mother. Gene inactivation by mutation is therefore inefficient because when one copy is inactivated, the second copy usually remains active and takes over.

In yeast, researchers have it easier: they use yeast cells in which all genes are present in only one copy (haploid yeast). Now Carette and co-workers have used a similar approach and used a human cell line, in which nearly all human chromosomes are present in a single copy.

In this rare cell line, Carette and co-workers generated mutations in almost all human genes and used this collection to screen for the host genes used by pathogens. By exposing those cells to influenza or to various bacterial toxins, the authors isolated mutants that were resistant to them. Carette then identified the mutated genes in the surviving cells, which code for a transporter molecule and an enzyme that the influenza virus hijacks to take over cells.

Working with Carla Guimaraes from Whitehead Member Hidde Ploegh's lab, Carette subjected knockout cells to several bacterial toxins to identify resistant cells and therefore the genes responsible.

The experiments identified a previously uncharacterized gene as essential for intoxication by diphtheria toxin and exotoxin A toxicity, and a cell surface protein needed for cytolethal distending toxin toxicity.

"We were surprised by the clarity of the results," says Jan Carette, a postdoctoral researcher in the Brummelkamp lab and first author on the Science article. "They allowed us to identify new genes and proteins involved in infectious processes that have been studied for decades, like diphtheria and the flu. In addition we found the first human genes essential for host-pathogen interactions where few details are known, as is the case for cytolethal distending toxin secreted by certain strains of E. coli. This could be important for rapidly responding to newly emerging pathogens or to study pathogen biology that has been difficult to study experimentally."

Brummelkamp sees the work as only the beginning.

"Having knockout cells for almost all human genes in our freezer opens up a wealth of biological questions that we can look at," he says. "In addition to many aspects of cell biology that can be studied, knockout screens could also be used to unravel molecular networks that are exploited by a battery of different viruses and bacteria."

This research was funded by Fundação para a Ciência ea Tecnologia (FCT) Portugal and the Kimmel Foundation.

Thijn Brummelkamp is a Fellow at Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted.


Story Source:

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


Journal Reference:

  1. jan E. Carette, Carla P. Guimaraes, Malini Varadarajan, Annie S. Park, Irene Wuethrich , Alzbeta Godarova, Maciej Kotecki, Brent H. Cochran, Eric Spooner, Hidde L. Ploegh and Thijn R. Brummelkamp. Haploid genetic screens in human cells identify host factors used by pathogens. Science, November 27, 2009

Cite This Page:

Whitehead Institute for Biomedical Research. "Knockouts in human cells point to pathogenic targets." ScienceDaily. ScienceDaily, 27 November 2009. <www.sciencedaily.com/releases/2009/11/091126173025.htm>.
Whitehead Institute for Biomedical Research. (2009, November 27). Knockouts in human cells point to pathogenic targets. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2009/11/091126173025.htm
Whitehead Institute for Biomedical Research. "Knockouts in human cells point to pathogenic targets." ScienceDaily. www.sciencedaily.com/releases/2009/11/091126173025.htm (accessed August 21, 2014).

Share This




More Plants & Animals News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Flower Power! Dandelions Make Car Tires?

Flower Power! Dandelions Make Car Tires?

Reuters - Business Video Online (Aug. 20, 2014) — Forget rolling on rubber, could car drivers soon be traveling on tires made from dandelions? Teams of scientists are racing to breed a type of the yellow flower whose taproot has a milky fluid with tire-grade rubber particles in it. As Joanna Partridge reports, global tire makers are investing millions in research into a new tire source. Video provided by Reuters
Powered by NewsLook.com
Unsustainable Elephant Poaching Killed 100K In 3 Years

Unsustainable Elephant Poaching Killed 100K In 3 Years

Newsy (Aug. 20, 2014) — Poachers have killed 100,000 elephants between 2010 and 2012, as the booming ivory trade takes its toll on the animals in Africa. Video provided by Newsy
Powered by NewsLook.com
Awesome New Camouflage Sheet Was Inspired By Octopus Skin

Awesome New Camouflage Sheet Was Inspired By Octopus Skin

Newsy (Aug. 19, 2014) — Scientists have developed a new device that mimics the way octopuses blend in with their surroundings to hide from dangerous predators. Video provided by Newsy
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